INTRODUCTION

Heavy Metals like copper, silver, zinc, cadmium, gold, mercury, lead, chromium, iron, nickel, tin, arsenic, sele- nium, molybdenum, cobalt, manganese, and aluminium are natural components of Earth’s crust, which cannot

ARTICLE INFORMATION:

*Corresponding Author: drshariqali@yahoo.com Received 20th July, 2015

Accepted after revision 30th November, 2015 BBRC Print ISSN: 0974-6455

Online ISSN: 2321-4007 NAAS Journal Score : 3.48

©A Society of Science and Nature Publication, 2015. All rights reserved.

Online Contents Available at: http//www.bbrc.in/

be degraded, therefore plants and animals have been exposed by them since the beginning of life on earth. Heavy metals are among the contaminants in the envi- ronment which are mainly librated by various human activities and have potential contribution to produce heavy metal toxicity. The history of heavy metal poison-

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Gajendra Mahor and Sharique A. Ali

ing has been reviewed many times in the books, research papers and reviews, whom all are stated that residual metals in the environment is a serious threat to animal, human health and aquatic ecosystem, (Ganrot et al., 1986; Cha et al., 1987; Baker et al., 1991; Jarup et al., 2003; Krewski et al., 2007; Yokel et al., 2008; Ezejiofor, et al., 2013; Miraj et al., 2014; Benouadah et al., 2015).

In all the heavy metals aluminium is most commonly used metal, abundantly distributed in our environ- ment and is most toxic to the various animals including humans. It was !rst produced experimentally in 1825 by the Danish chemist Hans Christian Oersted and later the German, French, and Austrian chemists Friedrich Woh- ler, Henri Sainte Claire Deville, and Carl Joseph Bayer upgraded isolation ef!ciencies and puri!cation tech- nologies. Due to its reactivity, aluminium is found only in combination with other elements like oxygen, silicon or "uorine that are commonly found in soil, minerals and rocks. (Lukiw et al., 2001; Verstraeten et al., 2008; Proudfoot et al., 2009; Kawahara et al., 2010, Negishi 2011; Hussein et al., 2013; Jefferson et al., 2014; Exley et al., 2015).

Human beings and animals they are naturally exposed to relatively large amounts of aluminium from food, water and air. Other Source of expose to aluminium in salt, deodorants, antacids, cookware, baking powder, processed cheeses, (Guilbert et al., 1986; Kosier et al., 1990; Yokel et al., 2001; Solfrizzi et al., 2003; Frank et al., 2009; Tchounwou et al., 2011; Darbre et al., 2013; Najar et al., 2014; Laghlimi et al., 2015).

Recently, however, aluminum toxicity has increased precipitously. Today, nearly 80% of those tested for metal toxicity reveal excessively high hair aluminium levels. It is linked with a number of disorders in man including Alzheimer’s disease, Parkinson’s, dementia and osteomalacia, neurological degenerative, muscu- lar dystrophy, multiple sclerosis and cancer, (Pignatti and Mariani, 2002; Kawahara et al., 2005; Verstraeten et al., 2008; Kumar and Gill, 2009; Turner et al., 2014; McGreevy et al., 2015).

Aluminium level in drinking water varies due to presence of aluminium coagulants 100 μg/L or greater, (Wettstein et al., 1991). Higher doses of aluminium con- sumed exceeds the body’s capacity to excrete it, the excess is then deposited in various tissues, including nerves, brain, muscle, bone, heart, liver, kidneys, spleen, testis, (Harrington et al., 1994; Stacchiotti et al., 2006).

It is completely useless or toxic for the human and other living organism or essential micronutrients but toxic when overdosed aluminium toxicity has been reported to impair the formation and release of par- athyroid hormone. The parathyroid glands concentrate aluminium above levels in surrounding tissues. Treat- ment of aluminium toxicity in renal failure patients

often reactivates hyperparathyroidism, which to a cer- tain extent is helpful for bone remodelling and healing, (Arieff et al., 1979, 1980; Leehey et al., 1985; Hendrick et al., 1992; Arieff, 1993; Kanwar et al., 1996; Pande 2006; Flora et al., 2008 Rebecca et al., 2014; Hegazy et al., 2015).

These metals have been found to be lethally hazard- ous to both animals and human above certain levels. it’s have been inevitably exposed to metals due to their ubiquity in nature, contaminated air, water, soil and food, wide use in industry and long-term persistence in the environment. These metals are also potent carcino- genic and mutagenic, (Patterson et al., 1965; Bugiani et al.,1982; Malluche 2002; Goncharuk 2012; Mohan et al., 2014; Clemente et al., 2015).

The pollution of the aquatic environment with metals has become a serious health concern because of their toxicity and accumulation by organisms, (Mendil et al., 2010; Shah et al., 2010). The greatest concern for alu- minium toxicity in North America occurs in areas that are affected by wet and dry acid deposition, such as eastern Canada and the north-eastern U.S. Acid mine drainage, logging, and metal levels in water treatment and soil, plant ef"uents can cause serious problems con- taining aluminium can be other major sources of Al, (DW et al., 1996).

In solution, the metal can combine with several dif- ferent agents to affect toxicity. aluminium is extremely common throughout the world and is innocuous under circumneutral or alkaline conditions. However, in acidic environments, it can be a major limiting factor to direct (toxic) and indirect (e.g. food chain) effects on wildlife vertebrates like !sh, amphibians, reptiles, birds and mam- mals, (Lewin et al., 1920; Sparling & Lowe., 1996; Anane and Creppy, 2001; Damien et al., 2004; Newairy et al., 2009; Akhigbe et al., 2011; Gibbons 2015).

The toxicity of aluminium has been studied exten- sively in !sh, less so in invertebrates, amphibians, and birds, and not at all in reptiles and free-ranging mam- mals. For aquatic organisms, Al bioavailability and tox- icity are intimately related to ambient pH; changes in ambient acidity may affect Al solubility, dissolved Al speciation, and organism sensitivity to Al. At moder- ate acidity (pH 5.5 to 7.0), !sh and vertebrates may be stressed due to Al adsorption onto gill surfaces and sub- sequent asphyxiation. At pH 4.5 to 5.5, Al can impair ion regulation and augment the toxicity of H+. alumin- ium toxic mode of action binding to functional groups both apically located at the gill surface and intracel- lularly located within lamellar epithelial cells disrupts the barrier properties of the gill epithelium. The gill is the principal target organ and results in accelerated cell necrosis, sloughing and death of the !sh, (Clark et al., 1985; Freda, 1989; Gensemer et al., 1999; Aurthman

et al., 2011; Maharajan & Parurukmani 2012; Slaninova et al., 2014; Abadi et al., 2015).

Aluminium sulphate is used as a mordant in dyeing, in the leather industry, paper industry, !re-proo!ng, waterproo!ng textiles, in antiperspirants and pesticides. After the use of aluminium sulphate in these industries it can be reached to underground water through soil par- tials and also seen in histopathological changes aquatic water bodies, where it exert toxic effect on !shes and amphibians, reptiles, birds and mammals liver, kidney, digestive system, respiratory system, nervous system, (Driscoll et al., 1980; Nyholm et al., 1981;Clark et al.., 1987; Exley et al., 1991; Peuranen et al., 1993; Howells et al., 1994; Gensemer et al., 1999; Freda 2001; Hadi et al., 2012; Govind et al. 2014; Gilani et al., 2015).

In amphibians, embryos and young larvae are typi- cally more sensitive than older larvae. Early-breeding amphibians, which lay eggs in ephemeral ponds and streams subject to spring runoff, are most at risk from Al and acidi!cation; those that breed later in the year in lakes or rivers are least vulnerable. Birds and mammals are most likely exposed through dietary ingestion of soil or Al-contaminated foods. Concentrations > 1000 mg. Kg-1 in food may be toxic to young birds and mammals. Clinical sing in these animals are consistent with rickets because Al precipitates with P in the gut. Due to exces- sive use of agrochemicals and changing environmental conditions; aluminium are being accumulated in soils and are posing a serious threat to animals and human life. The main tissues targeted by them include: the liver, kidneys, bowel, brain and nervous system, spleen and testis. Dietary intake of heavy metals, Aluminium via bioaccumulation and biomagni!cations has long term expose detrimental harmful effects not only on human health, but also the entire food chain including the ver- tebrates and the invertebrates, (Sharma and Agrawal, 2005, Ali et al., 2007; Ali et al., 2009; Ali et al., 2012; Ali & Naaz 2013 and Ali, 2014).

Elevation in the liver enzymes (AST, ALT and ALP) was noticed in aluminium toxicity due to liver dys- function and disturbance in the biosynthesis of these enzymes which all are indicative of liver damage and thus impaired liver function, (Ajith et al., 2007). Transaminases are intracellular enzymes and the most sensitive biomarkers, released into the circulation after damage and necrosis of hepatocytes like AST and ALT can be used in the assessment of liver function. Alumin- ium caused a signi!cant elevation in the activity of ALP.

Increase in the activity of ALP can attributed to severe damage to cell membranes or increased permea- bility of plasma membrane. However, they reported that the increase in the activity of ALP in blood might be due to the necrosis of liver, kidney and lung. The aluminium treated group, (Klein et al., 1989; Chinoy et al., 2001;

Gajendra Mahor and Sharique A. Ali

Demerdash et al., 2004; Saied et al., 2014; Kalaiselvi et al., 2015).

Aluminium causes toxic effect on biochemical param- eters i.e. Plasma glucose, Urea, Creatinine, Cholesterol, Trigycerides, Total Protein showed an increasing trend because prolonged metallic stress in the experimental animals makes adaptation dif!cult and creates weak- ness, anemia. These parameters have been effectively used as potential biomarkers of aluminium toxicity to animals and human in the !eld of environmental bio- monitoring. The other toxic effects of these contami- nants are also known decrease to the antioxidant enzy- matic activity due to presence of ROS and vitamin C that are the indication of lipid peoxidation in certain animal and human beings, (Lagerwerft et al., 1974; Flora et al., 1986; Zaman et al., 1993; Kowalczyk et al., 2004; Vino- dhini and Narayanan, 2008; Newairy et al., 2009; Ashor et al., 2015).

Different doses of aluminium to rats signi!cantly decreased level of red blood cell count and white blood cell count, total haemoglobin due to cause of found ane- mia and results showing that erythrocyte life span and inhibition of haemoglobin synthesis. Microcytic anemia was due to iron de!ciency. High Al levels also leads to microcytic anemia as Fe is unable to reverse the Al asso- ciated anemia, it was deduced that Al interferes with the metabolism of Fe, (Kaiser et al., 1984).

High concentration of Al decreases the average osmotic fragility of red cells in animals with renal fail- ure, (Drueke et al., 1986b). In High Al levels in plasma and red cells also leads to severe anemia but it can be reversed by terminating the Al concentration, (Cannata et al., 1983; Basha et al., 2012; Ibrahim et al., 2012, Mahdy et al., 2012, Hore et al., 2014; Pfadenhauer et al., 2014 Kisnieriene et al., 2015).

Increased lipid peroxidation was reported in the rats consuming diets with AlCl3. Hematological parameters blood used for the determination of erythrocyte count, hemoglobin content and Hct, mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) values were studied according to Feldman et al., (2000). Total and differential leukocytic count Total leukocyte count was performed by using improved neubauer hemocy- tometer. Chronic exposure and inhalation of aluminium "ake powder leads to dilation and hypertrophy of the right side of the heart in male factory workers who eventually died (McLaughlin et al., 1962; Mitchell et al., 1961; Ghorbel et al., 2015).

The cardiac effects may have been secondary to pul- monary !brosis and poor pulmonary function, (Singh RB, et al., (1989). Patients of peripheral circulatory fail- ure induced due to aluminium phosphide poisoning were reported. Chief symptoms were vomiting and epigastric

Gajendra Mahor and Sharique A. Ali

pain. Sensorium was normal in most of the patients. This might be because of direct toxic action of phosphine on myocardium and later when phosphine gets excreted either through lungs or kidney leads to improvement in LV systolic function, (Gupta et al., 1995; Pandey et al., 2013; Elabbassi et al., 2014; Solgi et al., 2015).

Aluminium and Enzyme activities due to its high reactivity, Al3+ is able to interfere with several biologi- cal functions, including enzymatic activities in key met- abolic pathways, (Akeson et al., 1989). Salts of Al may bind to DNA and RNA, inhibit such enzymes as hexoki- nase, acid and alkaline phosphatases, phosphodiesterase and phosphooxydase Al intoxication through the inhi- bition of kinase enzyme has been reported. Hexokinase is a Mg-ATP dependent enzyme that catalyzes the !rst step involved in glucose utilization, (Ward et al., 2012).

Al-ATP is a competitive inhibitor of hexokinase against the natural sustrate Mg-ATP. The inhibition of hexokinase activity in testis caused by aluminium might be related to minimization of glucose uptake and utili- zation by germ cells, (Pandey et al., 2013; Chen et al., 2014; Mohammad et al., 2015).

Aluminium toxicity may result in a drastic reduction or a complete failure of spermatogenesis and steroido- genesis by following ways. First Aluminium may block voltage sensitive calcium channels in hypothalamus cells and decreased the GnRH secretion which further responsible for the decrease in FSH and LH in pituitary as GnRH synthesis and secretion also depends on Ca2+, (Platt et al., 1994; Shahraki et al., 2004). Decreased level of FSH and LH disrupts the process of spermatogenesis and secretion of testosterone by Leydig cells.

Secondly, FSH and LH exert their actions on ster- oidogenesis by mainly regulating intracellular Ca2+ con- centration through Voltage-Dependent Ca2+ Channels (VDCCs) in Sertoli cells and Leydig cells, (Lee et al., 2011; Mehranjani et al., 2012; Zanatta et al., 2013 Zhao et al., 2014; Prabsattroo et al., 2015).

Now-a-day’s aluminium toxicity is a widespread problem facing all over the world in all forms of living organism, vertebrates like !sh, amphibians, reptiles, birds, mammals, animals and including humans, degradation of the environment and health. Over millions of reference articles on aluminium toxicity exist various data bases as of 1900 to 2015, all recognizing the aluminium toxicity.

IMPORTANT ROLE OF PLANT EXTRACTS IN DETOXIFICATION OR AMELIORATING THE EFFECTS OF ALUMINIUM TOXICITY

Nevertheless the fact that the phytochemicals contain plenty of "avonoids and polyphenols like antioxidants, they may also help ameliorate the heavy metals medi- ated toxicity in human and other animals.

Coriandrum sativum belongs to the family Umbellif- erae, known for its carminative and cooling properties. Its coriander extracts have phenolic compounds and "a- vonoides, these compounds contribute to the antioxida- tive activity, (Wangensteen et al., 2004). Phenolic sub- stances such as "avonoids, cumarins, cinnamic acid and caffeicacids are believed to have antioxidant properties, which plays an important role against degeneration, (Wiseman et al., 2000).

Coriander seed’s aqueous extract showed protection and an improvement in therapeutic action on pyramidal cell of cerebral cortex against neurodegenerative disor- ders and Alzheimer’ disease induced by aluminium chlo- ride treatment, (Enas et al., 2011). Antioxidant activity of coriander seed aqueous extract, was due to antioxidant enzymes which promoted oxygen to the brain, which could prevent oxidative damage caused by interaction between aluminium cation and unstable oxygen from abnormal mitochondria and protect pyramidal cells in cerebral cortex against damage induced by aluminium chloride overload, (Walton et al., 2007; Lu et al., 2013; Aslani et al., 2014; Benso et al., 2015).

Wattakaka volubilis which belongs to Asclepiadaceae family it is a tall wood climber which is densely densely lenticulate branches, quite bene!cial for amelioration of metal toxicity, (Yogita et al., 2013). occurring through- out the warmer regions of India and Nicobar Islands. W.volubilis (Linn) is used as a phytomedicine compound for liver diseases, (Rani et al., 2014). It has been also demonstrated that W. volubilis methanolic extract of powder form was very effective against the aluminium toxicity in rats, (Bais et al., 2015).

Clinical observation this study showed that enzy- matic analysis and histological, biochemical, organ weight, body weight examination were carried out. The extract of Wattakaka volubilis (Linn) was found to pos- sess hepatoprotective activity in a dose dependent man- ner and the effect was comparable with silymarin, a standard drug.

The extract signi!cantly reduce the toxicity of Alu- minium sulphate caused in liver due to the presence of phytoconstituents such as alkaloids, sterols, tannins, triterpenoids and "avonoids which are also known hepatoprotectant. Wattakaka volubilis leaf extract showed the highest hepatoprotective activity in against Aluminium Sulphate induced hepatotoxicity. The pos- sible action may be due to its hepatoprotective constitu- ents and antioxidant compounds present in the extract, (Rani et al., (2014).

Bacopa monniera (B. monniera), A small creep- ing herb locally known as ‘Brahmi’ in India, belongs to the family of Scrophulariaceae, and is mostly found throughout India, B. monniera have been recommended by ancient Ayurvedic for the treatment of neurological

disorders associated with free radical induced damages, (Stough et al., 2001). it has been demonstrated that in the Journal of Alzheimer’s Disease examines the evi- dence for the so-called aluminum hypothesis and !nd binds to DNA, gene expression and enzymes present in energy metabolism disrupts the proteins from cells, structural like Skeleton fatal effect on nerve !bers in the human brain result that nerve cells damaged and increased risk of Alzheimer’s disease, (Russo & Borrelli et al., 2005; Murthy et al., 2013; Kongkeawa et al., 2014; Rajan et al., 2015).

Jasonia candicans & Jasonia montana which belong to Asteraceae are well known detoxi!cation agents. Their extracts have displayed the potent effects against Al toxicity due to their anti-cholinesterase activity, anti- in"ammatory action, antioxidant capacity in addition to anti-amyloidogenic potential and neurotrophic effect, (Soliman et al., 2009).

Polyphenols are abundant in Jasonia montana and are used as antioxidants. Ethanolic extract of Jasonia candicans and Jasonia montana were used in regres- sion of the neurodegeneration characteristics of Alzhe- imer’s disease, (Hussein et al., 2011). High content of terpenes, sesquiterpenes and "avonoids in the ethanolic extract of the selected plants was responsible for the anticholinesterase activity, anti-in"ammatory action, antioxidant capacity and neurotrophic effect of these extracts, (Kim et al., 2012). Elevation in brain (Cox-2) gene expression Acetylcholinesterase (AchE) activ- ity, Tumour Necrosis Factor (TNF- ), Transforming Growth Factor Ε (TGF-Ε) and 8 hydroxydeoxyguanosine (8-OHdG). Growth Factor (IGF-1) was reported in experi- mental animal having Al toxicity, (Ahmed et al., 2013, 2014; Razavi et al., 2015).

Amelioration by Jasonia montana against lipid per- oxidation in liver and kidney of iron-overloaded rats has been reported byHussein et al., (2010). The decreased activity of brain marker Acetylcholinestrase (AchE) is direct indication of oxidative damage resulting in free radical generation. Treatment with therapeutic agents (Triphala and garlic) caused reversal of the biochemical parameters thereby recouping the variables towards nor- mal levels, (Sinha et al., 2011). Triphala is a traditional ayurvedic herbal formulation consisting equal parts of three medicinal plant fruits namely Terminalia chebula, Terminalia bellerica, Emblica of•cinalis. Triphala has been used E.of•cinalis has been reported as a rich source of vitamin C, which plays an important role in scavenging free radicals properties of Triphala, (Jagetia et al., 2002; Selvakumar et al., 2006; Mukherjee et al., 2006 Baliga et al., 2012; Bafna et al., 2013; Reddy et al., 2014; Gupta et al., 2015).

Garlic (Allium sativum L.) is one of the oldest Indian medicinal plant Garlic its has been valued for centuries

Gajendra Mahor and Sharique A. Ali

for its medicinal properties. Garlic (Allium sativum L.) is one of the earliest known medicinal plant (Metwally et al., 2009) possesses many healthful properties that are related to its bioactive compounds, vitamins and min- erals and trace elements (Selenium and Germanium). a wide range of medicinal properties,immunomodulatory hepatoprotective, antimutagenic and anticarcinogenic effects.

Reviews have shown that garlic can protect us from various pollutants and heavy metals like arsenic and lead Depending on personal requirements or prefer- ences, garlic supplements are available in a wide range of potencies, (Gupta et al., 2015).

The plant extract of Triphala and Garlic per se and in combination were used to treat aluminium poised mice. concurrent use of garlic and Triphala dry powder reduced aluminum concentration indicating the poten- tial activity in combination against alunimium toxic- ity in albino mice, (Cha et al., 1987; Sinha et al., 2011; Eteng et al., 2012; Ranjbar et al., 2013; Ting et al., 2014; Niino et al., 2015).

Turmeric (Curcuma longa) which belongs to Zingib- eraceae family is a rhizomatous herbaceous perennial plant. The active constituents are turmerone oil and water soluble curcuminoids, including curcumin, (Kim et al., 2001; Sandur et al., 2007). Curcumin is the princi- pal curcuminoid and is responsible for the yellow color of the turmeric root, (Shishodia et al., 2005; Yang et al., 2005). Turmeric is anti-in"ammatory, antiseptic, and antibacterial and has long been used in the Indian sys- tem of medicine to treat a variety of conditions and also helps in detoxi!cation of liver, balance cholesterol lev- els, !ght allergies, stimulate digestion, and boost immu- nity, (Chainani et al., 2003). Epidemiologic studies show a 4.4-fold lower incidence of AD in Southeast Asian countries where turmeric is commonly used as a dietary spice. Turmeric undergoes metabolism in the liver par- ticularly via glucuronidation, (Sikha et al., 2015).

The metabolites of Turmeric such as glucoronides appear to lack any pharmacological activity. The sys- temic elimination of Turmeric is another contributing factor for low bioavailability. Protective effects dem- onstrated (Ghoneim et al., 2002) by curcumin against ischaemia/reperfusion insult in rat forebrain. The initial review reports demonstrated by Wahlstorm and Blennow result showed that after giving the oral administration of 1g/kg curcumin to rats, more than 75% of curcumin was excreted in feces and negligible amount was detected in urine of animal model, (Wahlstrom and Blennow, 1978). Turmeric Showed that Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and !setin in a 6-OHDA model of PD may be related to their antioxidant capabilities and their capability to penetrate into the brain (Parkinson’s dis-

Gajendra Mahor and Sharique A. Ali

ease), (Olanow et al., 1999; Zbarsky et al., 2005; Lang et al., 2006; Kumar et al., 2014; Lin et al., 2015).

Ashwagandha (Withania somnifera) which belongs to Solanaceae has been used extensively in Ayurveda as a nervine tonic, aphrodisiac, and ‘adaptogen’ and helps the body adapt to stress, (Mishra LC, et al., 2000). It has rejuvenative (rasayana), antioxidant activity, free radical scavenging activity. Alkaloid extract of Ashwagandha root exhibited a calming effect on the central nervous system (CNS). Ashwagandha contains varities of ster- oidal compounds, amino acids (including tryptophan), and high amounts of iron, (Russo et al., 2001; Kelley et al., 2008; Wollen et al., 2010). One of the components, Withanamides has been shown to scavenge free radi- cals generated during the initiation and progression of AD. Neuronal cell death triggered by amyloid plaques was also blocked by with anamides, (Dhuley et al., 1998; Parihar et al., 2003).

Ashwagandha has been reported to increase memory and learning, (Tohda et al., 2005). Aqueous extracts of this herb have been found to increase cholinergic activ- ity, including increases in the acetylcholine content and cholineacetyl transferase activity in rats, (Schliebs et al., 1997; Tohda et al., 2000; Kuboyama et al., 2002). Treat- ment with the methanol extract of Ashwagandha caused neurite outgrowth in a dose- and time-dependent man- ner in human neuroblastoma cells and induced signi!- cant regeneration of both axons and dendrites, (Singh et al., 1982; Kuboyama et al., 2005 Singh et al., 2011; Haque et al., 2013; Prabu et al., 2014; Chitra et al., 2015).

Ginger which belongs to Zingiberaceae family (Zin- giber of•cinale Roscoe) is one of the most commonly used herbal tea ginger is rich in a large number of bioac- tive substances, including gingerols and shogaols, phe- nolic ketone derivatives. Ginger is used medicinally for its hepatoprotective and antioxidant, antidiabetic and hypolipidemic and anti-obesity effects. the protective effect of ginger due to lowering of the enhanced activity of AST and ALT in treated mice, (Moselhy et al.,2012; Mahmoud et al.,2013; Ala!atayo et al.,2014; Kalaiselvi et al.,2015).

Allium cepa has been associated with reduced lipid peroxidation index (malondialdehyde (MDA) and increased superoxide dismutase (SOD). Al-induced changes on reproduction pro!le such as hormones, sperm quality and lipid peroxidation was reversed by A.cepa, (Ige and Akhigbe, 2012). Phytochemical screening of A. cepa showed that it contains abundant "avonoids, and weak saponins, tannins, glycosides, sterols, and triter- penoids, (Achary et al., 2008). Allium cepa "avonoids reduced testosterone level; they improved the sperm quality by preventing lipid peroxidation. Allium cepa inhibited testosterone synthesis at the testicular level probably by inhibiting cholesterol conversion. Effects on

the female reproductive systems can include such things as menstrual problems, altered sexual behavior, infertil- ity, altered puberty onset, altered length of pregnancy, lactation problems, altered menopause onset and preg- nancy outcome, (Qin et al., 2013: Vahdani and Khaki 2014; Rajeshwari et al., 2015).

Oral Al exposure during pregnancy can cause a syn- drome including growth retardation, delayed ossi!ca- tion, and malformation at Al doses that also reduced maternal weight gain. At the perinatal age, aluminum is highly neurotoxic and inhibits prenatal and postnatal brain development. In addition, maternal dietary expo- sure to excess aluminum during gestation and lacta- tion which did not produce maternal toxicity would be capable of causing permanent neurobehavioral de!cits in weanling mice and rats, (Golub et al., 1986; Hussein et al., 2013; Muhammed et al., 2014; Berihu et al., 2015).

Rosmarinus of•cinalis commonly known as Rose- mary which belongs to lamiaceae. Their extract contains a high amount of total phenolics, is able to donate elec- trons, and therefore should be able to donate electrons to reactive radicals, converting them into more stable and unreactive species, (Dorman et al., 2003). The protec- tive action by rosemary extract in brain tissue through decreases in NOS activity, and subsequently, NO pro- duction. Therefore, they suggest that rosemary extract has an antioxidant effect as a free radical scavenger in this organ rosemary contains essential oils, terpenoids, "avonoids and alkaloids. Some of its constituents such as rosmarinic acid (RA) have been reported as powerful antioxidant protecting against free radicals damage and to reduce hepatotoxicity other researchers revealed the potential of RA for prevention of neurodegenerative dis- eases such as stroke, AD and PD, usually caused by an excess of free radicals. Unlike many drugs and natural antioxidants, RA was found to be able to cross blood brain so called pathologically activated-therapy, (Lip- ton, 2007; Weiss et al., 2009; Mahdy et al., 2012; Fathia et al., 2013; Jennifer et al., 2014; Loto et al., 2015).

CONCULSION AND FUTURE PERSPECTIVES

Previous reviews and this recent update on aluminium toxicity demonstrate that use of aluminium is on a sig- ni!cant rise and it is not safe but the accumulation of aluminium in the body has yet to become the subject of serious investigation and consideration in medicine. Considering this state of affairs, the present review has tried to provide compiled reports and summarised state- ments to evaluate the protective effects of medicinal plant extracts like Coriandrum sativum , Wattakaka vol- ubilis, Bacopa monniera, Jasonia candicans and Jaso- nia Montana, Terminalia chebula, Terminalia bellerica,

Emblica of•cinalis, Curcuma longa, Withania somnifera Zingiber of•cinale, Roscoe, Allium cepa and Rosmari- nus of•cinalis extracts against the toxic effects of the highly hubiquitous metal aluminium which is increas- ing in animals and human beings leading to serious health problems. To combat with this malady, medicinal plants can be potent drugs which, have the potential of antitoxic, antioxidant, detoxi!cation with amelioration effects against heavy metals.

Medicinal plant extracts have a considerable role to play in the amelioration of Al toxicity in animals and human caused by higher Aluminium accumula- tion in body organ Use of Al was increasing day by day and it become a recent hazard, by it excessive use. Even though, till quite recently, at the molecular level, our understanding of how aluminium exert these toxic effects is still rudimentary. There is a general consen- sus that proteins are key targets of aluminium. Metals interfere with the biological activity of native, folded proteins through diverse modes of interaction; they may bind to free thiols or other functional groups in proteins displace essential metal ions in metalloproteins; or cata- lyze oxidation of amino acid side chains. In this situ- ation, the need of the hour is to develop safe and non toxic natural detoxi!cation agents which can be used for amelioration of ever increasing metal exposure and toxicity These earlier and recent studies reviewed here, make us strongly believe that natural supplementation perspective, though observed in animal model, will have sustainable curative value among the already af"icted populations, neutralizing impact on freshly emerging metal toxicity scenario and possible proactive protec- tion to those potentially susceptible to aluminium expo- sure. Indian herbs have high potential in overcoming Al toxicity in animal models. It hold extreme promise for future treatment of Al toxicity in animals and human.

ACKNOWLEDGEMENT

GM is thankful to UGC New Delhi for awarding RGNF, Vide File No.2014-15-SC-MAD-67686/ 2014

REFERENCES

Achary V.M., Jena S, Panda K.K., Panda B.B. (2008). Alumin- ium induced oxidative stress and DNA damage in root cells of Allium cepa L. Ecotoxicol Environ Saf. 70(2):300-10.

Ahmed H. H., Booles H.F., Khalil W.K.B., Ashmaoui H.M.El., Othman S.M. (2013).Possible Therapeutic Role of Jasonia can- dicans and Jasonia montana Extracts in The Regression of Alzheimer’s Disease in Experimental Model. Ame. J. of Bioche. & Biotech. Vol.9, Issue 2.pp. 144-161.

Ahmed H.H., Salem A.M., Sabry G.M., Husein A.A., Kotob S.E. (2014). Medicinal plants offer multimechanistic approaches in

Gajendra Mahor and Sharique A. Ali

management of Alzheimer’s disease. J. of Che. and Pharm. Res. 6(11):879-892.

Ajith T.A., Hema U, Aswathy M.S. (2007). Zingiber of•cinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant Status. Food and Chemical Toxicology. 45:2267-2272.

Akeson M.A., Munns D.N., Burau R.G. (1989). Adsorption of Al+3 to phosphatidylcholine vesicles. Biochimica et Biophysica Acta 986. 33-40.

Akhigbe R.E., Olatunji L.A., Soladoye A.O., Oyeyipo IP. (2011). Effect of angiotensin1-converting enzyme inhibitor, capto- pril, on body weight, and food and water consumption in oral contraceptive-treated rats. Am J Biochem Mol Biol 1: 95-100.

Ala!atayo A.A., Syahid A., Mahmood M. (2014). Total Anti- Oxidant Capacity, Flavonoid, Acid and Polyphenol Content in Ten Selected Species of Zingiberaceae Rhizomes. Afr Tradit Complement Altern Med. 11(3): 7-13.

Alfrey A.C, Hegg A., Craswell P. (1980). Metabolism and toxic- ity of aluminum in renal failure. Am J Clin Nutr 33(7):1509- 1516.

Alfrey A.C. (1993). Aluminum toxicity in patients with chronic renal failure. Ther Drug Monit. 15(6):593597.

Alfrey A.C., LeGendre G.R., Kaehny WD. (1976).The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med. 294(4):184-8.

Ali A.S, Khan I., Ali S.A. (2007). Toxicological monitor- ing using earthworms. Toxicology and Science of Poisons, Avishkar Publication jaipur 167-186.

Ali A.S. (2014). Responses of the earthworm Eisinia foetida coelomocytes to aluminium chloride using the neutral red retention assay Biosc.Biotech.Res.Comm. Vol. 7 (1) 42-45.

Ali A.S., Khan I., Ali S.A. (2009). Bioremediations of con- taminated soil using earthworms. In Handbook of Agriculture Biotechnology Ed DK Maheshwari. Ali A..S, Naaz I (2013). Earthworm Biomarkers: The new tools of environment impact assessment. Biosc Biotech Res Comm 6: 163-169.

Ali S.A., Mitra J., Ali A.S. (2012). Biochemical markers for tox- icological assessment. A review In: The ugly face of Environ- ment, Delhi Publication New Delhi, 135-145.

Arieff A.I., Cooper J.D., Armstrong D. (1979). Dementia, renal failure, and brain aluminum. Ann Intern Med 90(5):741-747.

Ashor A.W., Siervo M., Lara J., Oqqioni C., Afshar S., Mathers J.C. (2015).Effect of vitamin C and vitamin E supplementation on endothelial function: a systematic review and meta-analy- sis of randomised controlled trials. Br J Nutr.113(8): 1182-94.

Aslani A., Ghannadi A., Khala! Z. (2014). Design, formulation and evaluation of green tea chewing gum. Adv Biomed Res.3: 142.

Bafna P.A and Balaraman R. (2013). Protective effect of DHC- 1, a Polyherbal formulation, against CCL4 induced Liver dam- age. Hygeia. Journal for drugs and medicines 5:10-18.

Bais S., Gill N. S., Kumar N., (2015). Neuroprotective Effect of Juniperus communis on Chlorpromazine Induced Parkin-

Gajendra Mahor and Sharique A. Ali

son Disease in Animal Model. Chinese Journal of Biology Vol. 2015, Article ID 542542, 7 p.

Baker A.J.M., Brooks R.R. (1989).Terrestrial higher plants which hyperaccumulate metal elements- A review of their dis- tribution, ecology and phytochemistry. Biorecovery 1: 81-126.

Baker A.J.M., Reeves R.D., McGrath S.P. (1991). In situ decon- tamination of heavy metal polluted soils using crops of metal accumulating plants—a feasibility study. p. 539–544. In R.E. Hinchee and R.F. Olfenbuttel (ed.) In Situ Bioreclamation. But- terworth Heinemann Publishers, Stoneham, MA.

Baliga M.S., Meera S., Mathai B., Rai M.P., Pawar V., Palatty P.L. (2012). Scienti!c validation of the ethnomedicinal proper- ties of the Ayurvedic drug Triphala: a review. Chin J Integr Med.18(12):946-54.

Benso B., Rosalen P.L., Alencar S.M., Murata R.M. (2015). Malva sylvestris Inhibits In"ammatory Response in Oral Human Cells. An In Vitro Infection Model. PLoS One.10 (10): e0140331.

Berihu B.A., Afwerk M., Debeb Y. G., Gebreslassie A. (2015). Review on Histological and Functional Effect of Aluminium Chloride on Cerebral Cortex of the Brain. Int.J. of Pharm Sci. and Research (IJPSR) Vol. 6 No.8.pp 1-12.

Bugiani O., Ghetti B. (1982). Progressing encephalomyelopathy with muscular atrophy, induced by aluminum powder. Neuro- biol Aging. 3(3):209-22.

Cannata J.B., Fernandez-Soto, I., Fernandez-Menezes, M.J., Fernandez-Martin, J.L., McGregor, S.J., Brock, J.H., Halls, D., (1991). Role of iron metabolism in absorption and cellular uptake of aluminium. Kidney Int. 39, 799–803.

Cha C.W. (1987). A study on the effect of garlic to the heavy metal poisoning of rat. J. Korean Med Sci. 2(4): 213-24.

Chainani N. (2003). Safety and anti-in"ammatory activity of Curcumin component of turmeric (Curcuma longa). J Alter Compl Med.9:161-8.

Chen T., Ning D., Sun H., Li R., Shang M., Li X., Wang X., Chen W., Liang C., Li W., Mao Q., Li Y., Deng C., Wang L., Wu Z., Huang Y., Xu J., Yu X. (2014). Sequence Analysis and Molecular Characterization of Clonorchis sinensis Hexokinase, an Unusual Trimeric 50-kDa Glucose-6-Phosphate-Sensitive Allosteric Enzyme. PLoS One. 9(9):107940.

Chitra B., Ramaswa R. (2015). An overview on the role of siddha practices in the prevention and management of age related neurodegenerative disorders with special reference to senile dementia. Indo. Amer. Jour. of Pharm. Res.5 (4):1510- 1521.

Clemente R., Pardo T., Madejon P., Madejon M., Bernal M.P. (2015). Food byproducts as amendments in trace elements contaminated soils. Food Research Interntional.Vol.73, p; 176-189.

Cunnigham S.D., Anderson T.A., Schwab P., Hsu F.C. (1996). Phytoremediation of soils contaminated with organic pollut- ants. Adv Agronomy 56: 55-114.

Das A., Dikshit M., Nath C. (2001). Pro!le of acetylcholine esterase in brain areas of male and female rats of adult and old age. Life Sci. 68:1545–1555.

Das A., Shanker G., Nath C., Pal R., Singh S., Singh H.K. (2002). A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba anti-cholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav.73:893e900.

Dhuley J.N. (1998). Effect of Ashwagandha on lipid peroxida- tion in stress-induced animals. J Ethnopharmacol.60:173–178.

Dorman H.J.D., Peltoketo A., Hiltunen R., and Tikkanen M.J. (2003).Characterization of the antioxidant properties of deo- dourised aqueous extracts from selected Lamiaceae herbs. Food Chem.83: 255-262.

Drueke T.B., Lacour M., Touam B., Jucquel J.P., Plachot J.J., Witmer G., Galle P., (1986). Effect of aluminum on hematopoe- sis. Kidney 29, 45–48.

Duruibe J.O., Ogwuegbu M. O., Egwurugwu J.N. (2007). J. N. Heavy metal pollution and human biotoxic effects. Interna- tional Journal of Physical Sciences Vol. 2 (5), pp.112-118.

Eidelberg D., Sotrel A., Joachim C., Selkoe D., Forman A., Pend- lebury W.W., Perl DP. (1987). Adult onset Hallervorden-Spatz disease with neuro!brillary pathology. Brain.110:993–1013.

Elabbassi W., Chowdhury M.A., Fachtartz A.N. (2014). Severe reversible myocardial injury associated with aluminium phosphide toxicity: A case report and review of literature. Journal of the Saudi Heart Association Volume 26, Issue 4, pp216–221.

Enas A., Khalil. (2011). Evaluation of the Possible Protective and Therapeutic In"uence of Coriander (Coriandum sativum L.) Seed Aqueous Extract on Hippocampal Pyramidal Cells Against Alzheimer’s Disease Induced by Aluminum Chloride in Adult Male Albino Rats. Researcher.3 (1):22-29. (ISSN: 1553-9865).

Eteng M.U., Onwuka F.C., Akpanyung E.O., Osuchukwu N.C., Bassey S.C. (2012). Reversal of cadmium induced toxicity fol- lowing dietary supplementation with garlic, ginger and cab- bage in male Wistar rats. J Nat Prod Plant Resour 2: 169-174

EZejiofor, Udebuani, Ezeji, Ayalogbu, Azuwuike, Adjero, Ihe- jirika, Ujowundu, Nwaogu, Ngwogu. (2013). Environmen- tal metals pollutants load of a densely populated and heav- ily industrialized commercial city of Aba, Nikeria. J. Toxicol. Environ. Health Sci. Vol.5 (1) pp.1-11.

Farina E., Fioravanti R., Chiavari L., Imbornone E., Alberoni M., Pomati S., Pinardi G., Pignatti R., Mariani C. (2002). Compar- ing two programs of cognitive training in Alzheimer’s disease: a pilot study. Acta Neurologica Scandinavica. 105:365–371.

Fathia A. M., Mohga S.A., Khaled G., Wahhab A., Mahitab I. (2013). Effect of some nutraceutical agents on aluminium- induced functional neurotoxicity in senile rats: I. Effect of rosemary aqueous extract and docosahexaenoic acid. Journal of Applied Sciences Research, 9 (3): 2322-2334.

Flora SJS., Tandon S.K .(2008). Preventive and therapeutic effects of thiamine. ascorbic acid and their combination in aluminium intoxication. Acta Pharmacol Toxicol 58: 374-8.

Frank, W. B. (2009). Aluminum Ullmann’s Encyclopedia of Industrial Chemistry. Wiley-VCH. doi:10.1002/14356007.a01_ 459.pub2.

Ganrot P.o. (1986). Metabolism and possible health effect of aluminium. Environ. Health, Perspect, 65: 363-441.

Garruto R.M., Shankar S.K., Yanagihara R., Salazar A.M., Amyx H.L., Gajdusek D.C. (1989). Low-calcium, high-alumi- num diet-induced motor neuron pathology in cynomolgus monkeys. Acta Neuropathol. (Berl).78:210–9.

Ghoneim AI., Naim A.B., Khalifa A.E., Denshary E.S. (2002). Protective effects of Curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacol Res.46:273–279.

Ghorbel I., Maktouf S., Kallel C., Chaabouni S.E., Boudawara T., Zeghal N. (2015). Disruption of erythrocyte antioxidant defense system, haematological parameters, induction of pro-in"ammatory cytokines and DNA damage in liver of co- exposed rats to aluminium and acrylamide. Chemico-Biologi- cal Interactions Vol.236pp.31-40.

Gibbons D., Morrissey C., Mineau P. (2015). A review of the direct and indirect effects of neonicotinoids and !pronil on vertebrate wildlife. Envi.l Sci. and Poll. Res. Vol.22, Issue 1, pp.; 103-118.

Golub M.S., Domingo J.L. (1996). What we know and what we need to know about developmental aluminum toxicity. J Toxicol Environ Health.48: 585-597.

Gorinstein S., Leontowicz H., Leontowicz M., Drzewiecki J., Najman K., Katrich E. Barasch D., Yamamoto k., Trakhtenberg S. (2006). Raw and boiled garlic enhances plasma antioxidant activity and improves plasma lipid metabolism in cholesterol- fed rats. Life Sciences.78:655 – 663.

Govind P., Madhuri S., Shrivastav A.B. (2014). Fish Cancer by Environmental Pollutants, 1st Edn., Narendra Publishing House, Delhi, India.

Guilbert, J. F., Park, C. F. (1986). The Geology of Ore Deposits. W. H. Freeman. pp. 774–795. ISBN 0-7167-1456-6.

Guo C.H., Lin C.Y., Yeh M.S., Hsu G.S.W. (2005). Aluminum- induced suppression of testosterone through nitric oxide pro- duction in male mice, Environment Toxicology Pharmacol- ogy.19:33- 40.

Gupta M.S., Malik A., Sharma V.K. (1995). Cardiovascular manifestations in aluminium phosphide poisoning with special reference to echocardiographic changes. J Assoc Physicians India 43 (11): 773-4, 779-80.

Gupta R., Gupta A., Singh R.L. (2015). Hepatoprotective Activi- ties of Triphala and Its Constituents. Int. J of Pharma Research & Review, 4(1):34-55.

Gupta V.K., Singh S., Agrawal A., Siddiqi N.J., Sharma B. (2015). Phytochemicals Mediated Remediation of Neurotoxic- ity Induced by Heavy Metals. Biochemistry Research Interna- tional Volume 2015, Article ID 534769, 9 pages.

Hadi A.A. and Alwan S.F. (2012). Histopathological changes in gills, liver and kidney of fresh water !sh, Tilpia zillii, expsed to aluminium. Int. J. of Pharm. & Life Sci. (IJPLS), Vol.3,Issue 11;2071-20812074

Hala A.H., Khattab, Inas, Z.A. Abdallah and Gehan, Kamel M. (2010).Grape seed extract alleviate reproductive toxicity caused

Gajendra Mahor and Sharique A. Ali

by aluminium chloride in male rats. Journal of American Sci- ence.6(12):1200-1209.

Hanna W.J., Grant C.L. (1962). Spectrochemical analysis of the foliage of certain trees and ornamentals for 23 elements. Bull Torrey Bot Club 89: 293-302.

Haque M.R., Ansari S.H., Rashikh A. (2013). Coffea arabica Seed Extract Stimulate the Cellular Immune Function and Cyclophosphamide-induced Immunosuppression in Mice.Iran J Pharm Res. 2013 Winter.12 (1): 101–108.

Harrington C., Wischilk C., McArthur F., Taylor G., Edwardson J. and Candy J.M. (1994): Alzheimer’s-disease-like changes in tau protein processing: association with aluminium accumula- tion in brains of renal dialysis patients. Lancet 343: 993-997.

Hashem FA. (2009). Camel’s Milk Protects against Aluminum Chloride-Induced Toxicity in the Liver and Kidney of White Albino Rats. American Journal of Biochemistry and Biotech- nology 5 (3): 98-108, ISSN 1553-3468.

Hendrick M.J., Goldschmidt M.H., Shofer F.S., Wang Y.Y., Somlyo A.P. (1992). Postvaccinal [after vaccination] sarcomas [cancer tumors] in the cat: epidemiology and electron probe microanalytical identi!cation of aluminum. 52(19):5391-4.

Hore P., Ahmed M., Nagin D., Clark N. (2014). Intervention model for contaminated consumer products: a multifaceted tool for protecting public health. Am J Public Health 104: 1377–83.

Hussein H., Mahmoud O.M. (2013). Effects of maternal admin- istration of aluminium chloride on the development of the skeletal system of albino rat foetuses protective role of Saffron. Eur. J. Anat. 17 (2): 63-71.

Hussein H.H., Mahmoud M. O. (2013). Effects of maternal administration of aluminium chloride on the development of the skeletal system of albino rat foetuses protective role of saf- fron. Eur. J. Anat. 17 (2): 63-71.

Hussein M.A. (2011). Potential mechanism for the antioxidant effects of Jasonia montana. J. of Pharm.Res. & Reviews 1, (1):19-28.

Hussein M.A., Farghaly H.S. (2010). Protective effects of Jaso- nia montana against lipid peroxidation in liver and kidney of iron-overloaded rats. Australian J. Basic Appl. Sci., ISSN, 4: 2004-2012.

Ige S.F, Akhigbe R.E. (2012).The role of Allium cepa on alumi- num-induced reproductive dysfunction in experimental male rat models. J Hum Reprod Sci. 5: 200-5.

Jagetia G.C., Baliga M.S., Malagi K.J., Sethukumar K.M. (2002). “The evaluation of the radio protective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to gamma- radiation.” Phytomed. 9 (2):99-108.

Jarup L. (2003). Hazards of heavy metal contamination. British Medical Bulletin 68: 167-182.

Jefferson Lab – Science Education (2014). Its Elemental: The

element aluminium. Retrieved from: http://education.jlab.org/ itselemental/ele013.html

Jennifer E., Slemmer and Weber J.T. (2014). Assessing Anti- oxidant Capacity in Brain Tissue: Methodologies and Limi-

Gajendra Mahor and Sharique A. Ali

tations in Neuroprotective Strategies. Antioxidants 3:636- 648.

Kaiser L., Schwartz, K., Hledin B., Mayor G. (1984). Microcytic anemia secondary to intraperitoneal aluminum in normal and uremic rats. Kidney Int. 26, 269–274.

Kalaiselvi A., Reddy G.A., Ramalingam V. (2015). Ameliorating Effect of Ginger Extract (Zingiber of•cinale Roscoe) on Liver Marker Enzymes, Lipid Pro!le in Aluminium chloride Induced Male Rats.IJPSPP.7 (1): 52-58.

Kalaiselvi A., Reddy G.A., Ramalingam V. (2015). Ameliorating Effect of Ginger Extract (Zingiber of•cinale Roscoe) on Liver Marker Enzymes, Lipid Pro!le in Aluminium chloride Induced Male Rats. Ind. J. of Pharm. Sci. And Drug Res. 7(1):52-58.

Kanwar VS., Jenkins J.J. Mandrell BN., Furman W.L. (1996). Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis. 27(1):64-7.

Kawahara M. (2005). Effects of aluminum on the nervous system and its possible link with neurodegenerative dis- eases. Journal of Alzheimer’s Disease.8 (2):171–182.

Kawahara M., Negishi K. (2011). Link between Aluminium and the Pathogenesis of Alzheimer’s Disease: The Integration of the Aluminum and amyloid cascade Hypotheses. Int. J. Alzheimers Dis.276393. PMCID: PMC3056430.

Kelley B.J., Knopman D.S. (2008).Alternative medicine and Alzheimer disease. Neurologist.14:299–306.

Kim D.S., Park S.Y., Kim J.K. (2001). Curcuminoids from Cur- cuma longa L. (Zingiberaceae) that protect PC12 rat pheochro- mocytoma and normal human umbilical vein endothelial cells from betaA(1–42) insult.Neurosci Lett.303:57–61.

Kim G., Hyo, Oh S., Myung, (2012). Herbal Medicines for the Prevention and Treatment of Alzheimer’s Disease. Cur. Pharma. Desi.Vol. 18, (19):57-75.

Kisnieriene V., Lapeikaite I. (2015). When chemistry meets biol- ogy: the case of aluminium - a review. CHEMIJA. Vol. 26. No. 3. P. 148-158.

Kongkeawa C., Dilokthornsakula P.,Thanarangsarita P., impe- anchoba N., Schol!elda, C.N. (2014). Meta-analysis of rand- omized controlled trials on cognitive effects of Bacopa mon- nieri extract. Journal of Ethnopharmacology Vol. 151, Issue 1, pp. 528–535.

Kosier J.H. (1990). Aluminum toxicity in the 1990. ANNA J. 26(4):423-4.

Krewski D., Yokel R.A., Nieboer E., Borchelt D., Cohen J., Harry J., Kacew S., Lindsay J., Mahfouz A.M., Rondeau V. (2007). Human health risk assessment for aluminium, aluminium oxide and aluminium hydroxide.J. Toxicol. Environ. Health B Crit. Rev. 10 (Suppl 1)1-269.

Kuboyama T., Tohda C., Komatsu K. (2005). Neuritic regenera- tion and synaptic reconstruction induced by withanolide A. Br J Pharmacol.144:961–971.

Kuboyama T., Tohda C., Zhao J., Nakamura N., Hattori M., Komatsu K. (2002). Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha. Neuroreport.13:1715–1720.

Kumar V. and Gill K.D. (2009). Aluminium neurotoxicity: neu- robehavioral and oxidative aspects, Archives of Toxicology 83; 965-978.

Kumar V., Gill K.D. (2014). Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its amelioration: A review. Neurotoxicology Vol.41, pp. 154-166.

Kutlubay R., Oguz E.O., Can B., Guven M.C., Sinik Z. and Tun- cay O.L. (2007). Vitamin E protection from testicular damage caused by intraperitoneal aluminium, International Journal of Toxicology.26:297-306.

Laden K., Felger C.B. (1988) Antiperspirants and deodorants: cosmetic science and technology series vol 7, Marcel Dekker, New York.

Laghlimi M., Baghdad B., Hadi H., Bouabdli A. (2015). Phytore- mediation Mechanisms of Heavy Metal Contaminated Soils: A Review Open Journal of Ecology, 5, 375-388.

Lang A. E. (2006). Randomized controlled trial of intraputa- menal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 59: 459–66.

Lee J.H., Ahn H.J., Lee S., Chan J., Min C.K. (2011). Effects of L- and T-type Ca2+ channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis, Journal of Assisted Reproduction and Genetics 28:23–30.

Leehey D.J, Daugirdas J.T., Ing T.S., Reid R.W. (1985). Spurious hyperphosphatemia due to hyperlipidemia. Arch Intern Med. 145(4):743-4.

Lewis W., Lewis M. P. F. (2003). Medical Botany; Plants Affect- ing Human Health, edition 2. John Wiley & Sons, Inc., Hobo- ken, New Jersey.45.

Lin W.T., Chen R.C., Lu W.W., Liu S.H., Yang F.Y. (2015). Protec- tive effects of low-intensity pulsed ultrasound on aluminum- induced cerebral damage in Alzheimer’s disease rat model. Scienti!c Reports 5, Article number: 9671.

Lipton, S.A. (2007). Pathologically activated therapeutics for neuroprotection. Nat. Rev. Neurosci.8: 803-808.

Lu H., Hu J., Li J., Pang W., Hu Y., Yang H., Li W., Huang C., Zhang M., Jiang Y.(2013). Optimal dose of zinc supplementa- tion for preventing aluminum-induced neurotoxicity in rats. Neural Regen Res.8 (29): 2754–2762.

Lu M. H., Kennedy G. L. (1986). Teratogenic evaluation of mancozeb in the rat following inhalation exposure. Toxicol. Appl. Pharmacol. 84: 355–68.

Lukiw W.J. (2001). Aluminum and gene transcription in the mammalian central nervous system. In: Exley C, editor. Alumi- num and Alzheimer’s disease, The Science That Describes the Link. New York, NY: Elsevier Press; p. 47–68.

Lunk H.J. (2015). Discovery, properties and application of chromium and its compounds. Chem. Texts.

Mahmoud R.H., Elnour W.A. (2013).Comparative evaluation of the ef!cacy of ginger and orlistat on obesity management, pancreatic lipase and liver peroxisomal catalase enzyme in male albino rats. European Review of Medicinal and Pharma- cological Sciences.17:75-83.

Malluche H.H. (2002). Aluminium and bone disease in chronic renal failure. Nephrol Dial Transplant.17;21-24.

Manna P.R., Chandrala S.P., Stocco D.M., (2006). Pindepend- ent signaling regulates steroidogenesis in mouse Leydig cells in the absence of StAR phosphorylation, Journal of Molecular Endocrinology 37:81-95.

McGreevy JW., Hakim CH., Mclntosh MA., Duan D. (2015). Animal models of Duchenne muscular dystrophy : from basic mechanisms to gene therapy. Model Mech. 8 (3): 195-213.

McLachlan D.R.C, Bergeron C., Smith J.E., Boomer D., Rifat S.L. (1996). Risk for neuropathologically con!rmed Alzhe- imer’s disease and residual aluminum in municipal drink- ing water employing weighted residential histories. Neurol- ogy.46:401–5.

McLaughlin A.I.G., Kazantzis G., King E., Teare D., Porter R.J. (1962). Pulmonary !brosis and encephalopathy associated with the inhalation of aluminum dust. Br J Ind Med 19:253-263.

Mehranjani M.S.,Tae! R. (2012). the protective role of vitamin E on the testicular tissue in rats exposed to sodium arsen- ite during the prenatal stage till sex maturity: A stereological analysis. Iran J Reprod Med.10 (6): 571–580.

Meinkoth J.H., Clinkenbeard K.D. (2000). Normal hematology of the dog. In: Feldman BF, Zinkl JG, Jain NC, eds. Schalm’s Veterinary Hematology. 5th ed. Baltimore, MD: Lippincott Wil- liams & Wilkins.1057-1063.

Metwally M.A.A. (2009). Effects of Garlic (Allium sativum) on Some Antioxidant Activities.in Tilapia Nilotica (Oreochromis niloticus). World Journal of Fish and Marine Sciences.1 (1): 56-64.

Miraj M., Jakkala L., Khan N., Ali A.S. (2014). On the toxicity of certain metals and its amelioration through herbal extracts. Biosci. Biotech. Res. Comm. 7 (2):99-107.

Mishra L.C., Singh B.B., Dagenais S. (2000). Scienti!c basis for the therapeutic use of Withania somnifera.(Ashwagandha): A review. Alternative Medicine Reviews.5:334–346.

Mitchell J., Manning G.B., Molyneux M. (1961). Pulmonary !brosis in workers exposed to !nely powdered aluminum. Br J Ind Med 18:10-20.

Mohammad N.S., Arafa M.H., & Atteia H.H. (2015). Coenzyme Q10 and !sh oil synergistically alleviate aluminum chloride- induced suppression of testicular steroidogenesis and antioxi- dant defense. Volume 49, Issue 11, pp 1319-1334.

Mohammed A., Kahtani A.l. (2010). Renal Damage Mediated by Oxidative Stress in Mice Treated with Aluminium Chlo- ride.Protective Effects of Taurine. Journal of Biological Sci- ences.10: 584-595.

Mohan, Sarswat, Yong, Pittman (2014). Organic and inorganic contaminants removal form water with biochar, a renewable, low cost and sustainable adsorbent-A critical review. Biore- sour. Technol. Bioretech. 01;120.

Moselhy W.A., Helmy N.A., Halim B.R., Nabil T.M., Hamid M.I. (2012). Role of ginger against the reproductive toxicity of alu- minium chloride in albino male rats. Reprod Domest Anim. 47(2): 335-345.

Gajendra Mahor and Sharique A. Ali

Mukherjee P.K., Rai S., Bhattacharyya S., Debnath P.K., Biswas T.K., Jana U., Pandit S., Saha B.P. and Paul P.K. (2006).Clini- cal Study of Triphala – A Well Known Phytomedicine from India 2006 Iranian journal of pharmacology and therapeutics. 5:51-54.

Murthy S., Gautam M. K., Goel S., Purohit V., Sharma H., Goel R. K. (2013). Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats. Biomed Res Int. 972028.pp. 1-9.

Nathan P.J, Tanner S., Lloyd J., Harrison B., Curran L., Oliver C., Stough C. (2004). Effects of a combined extract of Ginkgo biloba and Bacopa monniera on cognitive function in healthy humans. Hum Psychopharmacol.19 (2):91-6.

Niino T., Arizaga M.V. (2015). Cryopreservation for preserva- tion of potato genetic resources. Breed Sci. 65(1): 41-52.

Olanow C.W., Tatton W.G. (1999). Etiology and Pathogenesis of Parkinson’s Disease. Annual Review of Neuroscience. Vol. 22:123-144.

Pande S., Ritter C.S., Rothstein M. (2006). FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation. Nephron Physiol. 104(1):p23-32.

Pandey G., Jain G.C. (2013). A Review on Toxic Effects of Alu- minium Exposure on Male Reproductive System and Probable Mechanism of Toxicity. Int. J. of Toxi. and Appl. Pharma.3(3): 48-57.

Parihar M.S., Hemnani T. (2003). Phenolic antioxidants atten- uate hippocampal neuronal cell damage against kainic acid induced excitotoxicity. J Biosci.28:121–128.

Paul B., Tchounwou P.B., Yedjou C.G., Patlolla AK., and Sut- ton J. D (2011). Heavy Metals Toxicity and the Environment. Indian J Pharmacol 43(3): 246–253.

Peruquetti R.L., Taboga S.R., Oliveira M.T.V. (2010). Expression of acid phosphatase in the seminiferous epithelium of verte- brates, Genetics and molecular research. 9; 620-628.

Pizent A., Tariba B., Zivkovic T., Reproductive toxicity of met- als in men, Archives of Industrial Hygiene and Toxicology 63: 35-46.

Platt B., Busselberg D. (1994). Actions of aluminum on volt- age-activated calcium channel currents, Cellular and Molecu- lar Neurobiology 14:819-829.

Prabsattroo T., Wattanathorn J., Iamsaard S., Somsapt P., Sri- tragool O., Thukhummee W., Muchimapura S. (2015). Moringa oleifera extract enhances sexual performance in stressed rats. J Zhejiang Univ Sci B.16 (3): 179–190.

Prabu P.C., Panchapakesan S. (2014). Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats. Drug and Chemical Toxicology. Vol.38, Issue1,pp.50-56.

Proudfoot A.T. (2009). Aluminium and zinc phosphide poison- ing. Clin Toxicol (Phila). 47(2):89-100.

Qin R., Jiang W., Liu D. (2013).Aluminum can induced altera- tion in the cellular localization and expression of three major nucleolar proteins in root tip cells of Allium cepa var. Agroga- rum L. Vol. 90. Issue 2, PP.827-834.

Gajendra Mahor and Sharique A. Ali

Rajan K.E., Preethi J.,Singh H.K. (2015). Molecular and Func- tional Characterization of Bacopa monniera: A Retrospective Review. Evid Based Complement Alternat Med.945217.12 p.

Rajeshwari A., Kavitha S., Alex S.A., Kumar D., Mukherjee A., Chandrasekaran N., Mukherjee A. (2015). Cytotoxicity of Alu- minium oxide nanoparticles on Allium cepa root tip-effects of oxidative stress generation and biouptate. Envioron. Sci. Pol- lut. Res. 22:11057-11066.

Rani S. U., Chitra M., Jainu M. (2014). Hepatoprotective Effect of Wattakaka volubilis Extract on Aluminium Sulphate Induced Liver Toxicity. International Journal of Pharmaceuti- cal Sciences and Drug Research.6 (2): 169-173.

Ranjbar S.H., Zahedi H.S., Abdollahi M., Larijani B. (2013). Trends in publication of evidence-based Traditional Iranian medicine in endocrinology and metabolic disorders. J Diabetes Metab Disord.12:49.

Raymond A., Wuana and Felix E., Okieimen (2011). Heavy Metals in Contaminated Soils: A Review of Sources, Chemis- try, Risks and Best Available Strategies for Remediation. ISRN Ecology Article ID 402647, 20p.

Razavi B.M., and Hosseinzadeh H. (2015). Saffron as an anti- dote or a protective agent against natural or chemical toxici- ties. Daru J. of Pharma. Sci. 23:31. pp. 1-9.

Rebecca M., Hoerth, Britta M., Seidt, ShahM., Schwarz C., Bettina M., Willie, Georg N. Duda, Fratzl P., Wagermaier W. (2014). Mechanical and structural properties of bone in non- critical and critical healing in rat. Acta Biomaterialia Volume 10, Issue 9; Pages 4009–4019.

Reddy P.N., Tammineni P., Radhika G.J., Reddy P.K., Pallu R. (2014). Hepatoprotective Effects of Terminalia chebula Fruit Extract against 2-AAF–Induced Hepatic Damage in Albino Mice: Role of MDR1 and COX-2. Journal of Herbs, Spices & Medicinal Plants 20:402-420.

Russo A., Izzo A.A., Cardile V., Borrelli F., Vanella A. (2001). Indian medicinal plants as antiradicals and DNA cleavage pro- tectors. Phytomedicine. 8:125–132.

Sahin E., Colla S., Liesa M., Moslehi J., Müller F.L., Guo M., Cooper M., Kotton D., Fabian A.J., Walkey C. (2011). Telomere dysfunction induces metabolic and mitochondrial compro- mise. Nature. 470:359–365.

Salt D.E., Smith R.D., Raskin I. (1998). Phytoremediation. Annu. Rev Plant Physiol Plant Mol Biol 49: 643-668.

Sandur S.K., Ichikawa H., Pandey M.K., Kunnumakkara A.B., Sung B., Sethi G, Aggarwal B.B. (2007). Role of pro-oxi- dants and antioxidants in the anti-in"ammatory and apop- totic effects of curcumin (diferuloylmethane) Free Radic Biol Med.43:568–580.

Schliebs R., Liebmann A., Bhattacharya S.K., Kumar A., Ghosal S., Bigl V. (1997) .Systemic administration of de!ned extracts from Withania somnifera (Indian Ginseng) and Shilajit differ- entially affects cholinergic but not glutamatergic and GABAer- gic markers in rat brain. Neurochem Int.30:181–190.

Selvakumar D., Srikumar R., Manikandan S., Parthasarathy N.J., and Rathinasamy S. (2006). Antioxidant property of

Triphala on cold stress induced oxidative stress in experimen- tal rats. Journal of Health science.52 (6)843-847.

Shahraki M.R., Zahedi A.S., Sarkaki A.R. (2004). The Effect of Aluminum Injection in Lateral Ventricle on Sex Hormones in Male Rat, Shiraz E-Medical Journal 5: 1-10.

Sharma, R.K. and Agrawal M. (2005). Biological effects of heavy metals: An overview. J. Environ Biol. 26(2): 301-313.

Shati A., Elsaid G., Hafez E. (2011). Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience.175:66e74.

Shin R.W., Kruck T.P., Murayama H., Kitamoto T. (2003). A novel trivalent cation chelator Feralex dissociates binding of aluminum and iron associated with hyperphosphorylated tau of Alzheimer’s disease. Brain Res.961:139–46.

Shin S.H., Kim M.K. (2004). Effect of dried powders or etha- nol extracts of Garlic "esh and peel on lipid metabolism and antithrombogenic capacity in 16- month-old rats. Hanguk Yongyang Hakhoechi. 37 (7), 515– 524.

Shiraki H., Yase Y. (1991). Amyotrophic lateral sclerosis and Parkinsonism-dementia in the Kii peninsula: comparison with the same disorders in Guam and with Alzheimer’s dis- ease, Handbook of Clinical Neurology, vol. 15, pp. 273–300.

Shishodia S., Amin H.M., Lai R., Aggarwal B.B. (2005). Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apop- tosis in mantle cell lymphoma. Biochem. Pharmacol.70:700–713.

Sikha A., Harini A., Hegde P.L. (2015). Pharmacological activi- ties of wild turmeric (Curcuma aromatic Salisb): a review. Journal of Phrmacognosy and Phytochemistry 3(5):01-04.

Singh N., Bhalla M., Jger P.D., Gilca M. (2011). An Overview on Ashwagandha:A Rasayana (Rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 8(5 Suppl): 208–213.

Singh N., Singh S.P., Sinha J.N., Shanker K., Kohli R.P. (1982). Withania somnifera (Ashwagandha) A rejuvenator herbal drug which enhances survival during stress (An adaptogen) Int J Crude Drug Res.3:29–35.

Singh R.B., Rastogi S.S., Singh D.S. (1989). Cardiovascular manifestations of aluminium phosphide intoxication. J Assoc Physicians India.37:590–2.

Singh T., Goel R.K. (2015).Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity. Neuro- toxicology, 49:1-7.

Sinha N., Sharma N., Johri S. (2011). Phytotherapeutic approach against aluminium induced biochemical changes in albino mice. Journal of Pharmaceutical Research and Opinion. 1: 4 121 – 125.

Skidmore-Roth L. (2003). Handbook of Herbs and Natural Sup- plements 2nd edition. Int. J. Of Food Microbio.83:331-335.

Solfrizzi V., Panza F., Capurso A. (2003): The role of diet in cognitive decline. J. Neural Transm. 110, 95-110.

Solgi R., Baghaei A., Golaghaei A., Hasani S., Baeeri M., Nav- aei M., Ostad S.N., Hosseini R., Abdollahi M. (2015). Electro-

physiological and molecular mechanisms of protection by iron sucrose against phosphine-induced cardiotoxicity: a time course study.Toxicology Mechanisms and Methods. Vol. 25 pp.249-257.

Soliman F.M., Moussa M.Y., Abdallah H.M., Othman S.M. (2009). Cytotoxic activity of "avonoids of Jasonia montana Vahl. (Botsch) (Astraceae) growing in Egypt. Australian J. Basic Appl. Sci.3: 148-152.

Sparling D.W. and Lowe TP., (1996). Environmental hazards of aluminum to plants, invertebrates, !sh, and wildlife. Rev Environ Contam Toxicol.; 145:1-127.

Stacchiotti A., Rodella L.F., Ricci F., Rezzani R., Lavazza A., Bianchi R. (2006): Stress proteins expression in rat kidney and liver chronically exposed to aluminium sulphate. Histol His- topathol, 21: 131-140.

Stough C., Lloyd J., Clarke J., Downey L.A., Hutchison C.W., Rodgers T., Nathan PJ. (2001).The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl).156(4):481-4.

Strong M.J., Garruto R.M.(1991). Chronic aluminium-induced motor neuron degeneration: clinical, neuropathalogical and molecular biological aspects. Can J Neurol Sci. 18(3): 428-31.

Styren S.D., Kamboh M.I., Dekosky S.T. (1998). Expression of differential immune factors in temporal cortex and cerebel- lum: the role of -1-antichymotrypsin, Apolipoprotein E, and reactive glia in the progression of Alzheimer’s Disease. J Comp Neurol. 396:511–20.

Sun H., Hu C., Jia L., Zhu Y., Zhao H., Shao B., Wang N., Zhang Z., Li Y. (2011). Effects of Aluminum Exposure on Serum Sex Hormones and Androgen Receptor Expression in Male Rats, Biological Trace Element Research. 144; 1050-1058.

Taylor G.A., Moore P.B., Ferrier I.N., Tyrer S.P. and Edwardson J.A. (1998).Gastrointestinal absorption of aluminium and cit- rate in man. J. Inorg. Biochem. 69, 165-169.

Ting H., Deep G., Agrawal C., Agrawal R. (2014). The strategies to control prostate cancer by chemoprevention approaches. Mutat Res.1-15.

Tohda C., Kuboyama T., Komatsu K. (2000). Dendrite extension by methanol extract of Ashwagandha (roots of Withania som- nifera) in SK-N-SH cells. Neuroreport.11:1981–1985.

Tohda C., Kuboyama T., Komatsu K. (2005). Search for natural products related to regeneration of the neuronal network. Neu- rosignals.14:34–45.

Tomljenovic L., Shaw C.A. (2012). Mechanism of aluminium adjuvant and auto immunity in pediateic population Journal of toxicology 21: 223-230.

Tripathi S., Mahdia A.A., Nawaba A., Chandera R., Hasanb M., Siddiquib M.S., Mahdic F., Mitrad K., Bajpaid V.K. (2009). In"u- ence of age on aluminum induced lipid peroxidation and neu- rolipofuscin in frontal cortex of rat brain: A behavioral, bio- chemical and ultrastructural study. Brain Res. 1253:107– 116.

Ugwoke CEC., Ezugwe CO. (2010). Phytochemical screening and promiximate composition and onion bulb (Allium cepa L). J Pharm Allied Sci.7, ISSN: 1596-8499.

Gajendra Mahor and Sharique A. Ali

Uversky V. N., Li J., Fink A. L. (2001). Metal-triggered struc- tural transformations, aggregation, and !brillation of human -synuclein: a possible molecular link between parkin- son’s disease and heavy metal exposure, Journal of Biological Chemistry, vol. 276, no. 47, pp. 44284–44296.

Vahdani V., Khaki A. (2014). Effect of Allium cepa Seed Extract on Serum Testosterone in Rats.Crescent Journal of Medical and Biological Sciences Vol. 1, No. 3, Summer 110-112.

Verbeeck RM., Driessens FC., Rotgans J. (1990). Aluminium in tooth pastes and Alzheimer’s disease. 87(2):141-4

Verstraeten S.V., Aimo L., and Oteiza P.I. (2008). Aluminium and lead: molecular mechanisms of brain toxicity, Archives of Toxicology 82; 789–802.

Vivek Kumar,1 Shweta Singh,1 Anju Agrawal,2 Nikhat Jamal Siddiqi,3 and Bechan Sharma1

Wahlström B., Blennow G.A. (1978). Study on the fate of Curcumin in the rat. Acta Pharmacol Toxicol (Copenh).43(2):86-92.

Walton J.R. (2007). An aluminum–based rat model for Alzhe- imer’s disease exhibits oxidative damage inhibition of PP2A activity, hyperphosphorylated and granulavacular degenera- tion. J Inorg Biochem. 101(9):1275-84.

Wangensteen H., Samuelsen A.B., Malterud K. E. (2004). Anti- oxidant activity in extracts from Coriander. Food Chem; 88: 293-297.

Ward P.S., Thompson C.B. (2012). Metabolic reprogramming: a cancer hallmark even warburg did not anticipate.Cancer Cell. 21:297–308.

Wettstein A. (1991) Failure to !nd a relationship between mnestic skills of octogenarians and aluminium in drinking water. International archives of occupational and environmen- tal health, 63:97-103.

Wiseman H., Okeilly, J.D., Aldlercreutz, H., Mallet, A.J., Bow- ery, E.A., Sanders, A.B. (2000). Iso"avones phytoestrogen con- sumed in soya decrease F2-isoprostane concentrations and increase resistance of low density lipoprotein to oxidation in humans. Am. J. Clin. Nutr; 72: 397-400.

Wollen K.A. (2010). Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev.15:223–244.

Yang F., Lim G.P., Begum A.N., Ubeda O.J., Simmons M.R., Ambegaokar S.S., Chen P.P., Kayed R., Glabe C.G., Frautschy S.A., Cole G.M. (2005). Curcumin inhibits formation of amy- loid beta oligomers and !brils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 280:5892–5901.

Yogita S., Prachi A., Arun J., Maya B. (2013). Antibacterial and Antifungal Activity of Roots of Wattakaka volubilis. Global J of Pharm.7 (3): 283-287.

Yokel R.A., Hicks C.L., Florence R.L. (2008). Aluminium bio- availability from basic sodium aluminium phosphate, an approved food additive emulsifying agent, incorporated in cheese. Food chem. Toxicol. 46:2261-2266.

Gajendra Mahor and Sharique A. Ali

Yousef M.I., Kamel I.K., Guendi I.E.E., Demerdash F.M. (2007). An in-vitro study on reproductive toxicity of aluminum chlo- ride on rabbit sperm: the protective role of some antioxidants, Toxicology 239.213- 223.

Yumoto S., Ngai H., Matsuzaki H., Kobayashi T., Tada W., Ohki Y. (2000). Transplacental passage of Aluminum from pregnant rats to fetus and aluminium transfer through maternal milk to milk suckling rats. Nucl Instrum Methods Phy Res B.172:925- 929.

Zanatta A.P., Zanatta L., Gonçalves R., Zamoner A., Silva F.R.M.B. (2013). Rapid Responses to Reverse T3 Hormone in

Immature Rat Sertoli Cells: Calcium Uptake and Exocytosis

Mediated by Integrin. PLoS One 8(10): e77176.

Zbarsky V., Datla K.P., Parkar S., Rai D.K., Aruoma O.I., Dexter D.T. (2005). Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and !setin in a 6-OHDA model of Parkinson’s disease. Free Radic Res.39:1119–1125.

Zhao X., Sheng L., Wang L., Hong J., Yu X., Sang X., Sun Q., Ze Y., Hong F. (2014). Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice. Part Fibre Toxicol.11: 47.