Toxicity of lead: a review with recent updates

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Lead poisoning has been recognized as a major public health risk, particularly in developing countries. Though various occupational and public health measures have been undertaken in order to control lead exposure, cases of lead poisoning are still reported. Exposure to lead produces various deleterious effects on the hematopoietic, renal, reproductive and central nervous system, mainly through increased oxidative stress. These alterations play a prominent role in disease manifestations. Modulation of cellular thiols for protection against reactive oxygen species (ROS) has been used as a therapeutic strategy against lead poisoning. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin and a few herbal extracts show prophylaxis against the majority of lead mediated injury in both invitro and in vivo studies. This review provides a comprehensive account of recent updates describing health effects of lead exposure, relevant biomarkers and mechanisms involved in lead toxicity. It also updates the readers about recent advances in chelation therapy and newer therapeutic strategies, like nanoencapsulation, to treat lead induced toxic manifestations.

Agarwal R, Goel SK, Behari JR. (2010). Detoxifi cation and antioxidant effectsof curcumin in rats experimentally exposed to mercury. J Appl Toxicol 30: 457-468.

Agency for Toxic Substances and Disease Registry (ATSDR). (2005) Toxicological profile for lead. (Draft for Public Comment). Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; pp.43-59.

Ahamed M, Siddiqui MKJ. (2007). Environmental lead toxicity and nutritional factors. Clin Nut 26: 400-408.

Ahamed M, Siddiqui MKJ. (2007). Low level lead exposure and oxidative stress: Current opinions. Clin Chim Acta 383: 57-64.

Ahamed M, Verma S, Kumar A, Siddiqui MK. (2005). Environmental exposure to lead and its correlation with biochemical indices in children. Sci Total Environ 346: 48-55.

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. (2007). Bioavailability of curcumin: problems and promises. Mol. Pharm. 4: 807-818.

Ayres JG. (2008). The eff ects of Inhaled materials on the lung and other target organs. Occupational Hygiene (Blackwell Publishing Ltd). pp. 47-58.

Beecher GR. (2003). Overview of dietary fl avonoids: nomenclature, occurrence and intake. J Nutr 133: 3248S-3254S.

Bellinger DC. (2004). Lead. Pediatrics 113: 1016-1022.

Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A. (2007). Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): A novel strategy for human cancer therapy. J Nanobiotech 5: 3-21.

Blokhina O, Virolainen E, Fagerstedt KV. (2003). Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review. Ann Bot 91: 179-194.

Bravo A, Anacona JR. (2001). Metal complexes of the fl avonoid quercetin: antibacterial properties. Trans Met Chem 26: 20-23.

Brent JA. (2006). Review of: “Medical Toxicology”. Clin Toxicol 44: 355-355.

Bressler J, Kim KA, Chakraborti T, Goldstein G. (1999). Molecular mechanisms of lead neurotoxicity. Neurochem Res 24: 595-600.

Chang BJ, Jang BJ, Son TG, Cho IH, Quan FS, Choe NH, Nahm SS, Lee JH. (2012). Ascorbic acid ameliorates oxidative damage induced by maternal low level lead exposure in the hippocampus of rat pups during gestation and lactation. Fd Chem Toxicol 52: 104-108.

Choudhuri T, Pal S, Das T, Sa G. (2005). Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem 280: 20059-20068.

Cleveland LM, Minter ML, Cobb KA, Scott AA, German VF. (2008). Lead hazards for pregnant women and children: Part 1: immigrants and the poor shoulder most of the burden of lead exposure in this country. Part 1 of a two-part article details how exposure happens, whom it aff ects, and the harm it can do. Am J Nurs 108: 40-49; quiz 50.

Cornelis R. (2005). Handbook of elemental speciation II: species in the environment, food, medicine & occupational health. Wiley.

Cory-Slechta DA. (1996). Legacy of lead exposure: consequences for the central nervous system. Otolaryngol Head Neck Surg 114: 224-226.

Dairam A, Limson JL, Watkins GM, Antunes E, Daya S. (2007). Curcuminoids, curcumin, and demethoxycurcumin reduce lead-induced memory defi cits in male Wistar rats. J Agric Food Chem 55: 1039-1044.

Daniel S, Limson JL, Dairam A, Watkins GM, Daya S. (2004). Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem 98: 266-275.

Das KK, Saha S. (2010). L-ascorbic acid and alpha tocopherol supplementation and antioxidant status in nickel- or lead-exposed rat brain tissue. J Basic Clin Physiol Pharmacol 21: 325-346.

De Araujo DP, Lobato Rde F, Cavalcanti JR, Sampaio LR, Araujo PV, Silva MC, Neves KR, Fonteles MM, Sousa FC, Vasconcelos SM. (2011). The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson’s disease: a review. Int J Neurosci 121: 51-57.

Dugas AJ Jr, Castaneda-Acosta J, Bonin GC, Price KL, Fischer NH, Winston GW. (2000). Evaluation of the total peroxyl radical-scavenging capacity of fl avonoids: structure-activity relationships. J Nat Prod 63: 327-331.

Durrani AI, Schwartz H, Nagl M, Sontag G. (2010). Determination of free α-lipoic acid in foodstuff s by HPLC coupled with CEAD and ESI-MS. Fd Chem 120: 1143-1148.

Flora SJS. (2002). Nutritional components modify metal absorption, toxic response and chelation therapy. J Nut Environ Med 12: 53-67.

Flora SJS. (2009). Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2: 191-206.

Flora SJS. (2011) Arsenic induced oxidative stress and its reversibility. Free Rad Biol Med 51: 257-281.

Flora SJS, Flora G, Saxena G. (2006). Environmental occurrence, health effects and management of lead poisoning. (In: Jose, S. C, Jose, S., eds. Lead. Amsterdam: Elsevier Science B.V.). pp. 158-228.

Flora SJ, Pande M, Mehta A. (2003). Benefi cial eff ect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication. Chem Biol Interact 145: 267-280.

Flora SJ, Flora G, Saxena G. (2007). Mishra, M. Arsenic and lead induced free radical generation and their reversibility following chelation. Cell Mol Biol (Noisy-le-grand) 53: 26-47.

Flora SJS, Gupta R. (2007). Benefi cial eff ects of Centella asiatica aqueous extract against arsenic-induced oxidative stress and essential metal status in rats. Phytother Res 21: 980-988

Flora SJS, Saxena G, Mehta A. (2007). Reversal of lead-induced neuronal apoptosis by chelation treatment in rats: role of reactive oxygen species and intracellular Ca2+. J Pharmacol Exp Ther 322: 108-116.

Flora SJS, Pachauri V, Saxena G. (2011). Arsenic, cadmium and lead. Reproductive and Developmental Toxicology. (Academic Press) pp 415-438.

Gandhi P, Khan Z, Chakraverty N. (2011).Soluble curcumin: A promising oral supplement for health management. J Appl Pharma Sci 1: 01-07.

Garcia MTA, Gonzalez ELM. (2008). Toxic eff ects of perinatal lead exposure on the brain of rats: Involvement of oxidative stress and the benefi cial role of antioxidants. Fd Chem Toxicol 46: 2089-2095.

Garza A, Vega R, Soto E. (2006). Cellular mechanisms of lead neurotoxicity. Med Sci Monit 12: RA57-65.

Grant LD. (2008). Lead and compounds. Environmental Toxicants (John Wiley & Sons, Inc.). pp. 757-809.

Guidotti TL, McNamara J, Moses MS. (2008). The interpretation of trace element analysis in body fl uids. Indian J Med Res 128: 524-532;.

Guidotti TL, Ragain L. (2007). Protecting children from toxic exposure: three strategies. Pediatr Clin North Am 54: 227-235.

Gurer H, Ercal N. (2000).Can antioxidants be benefi cial in the treatment of lead poisoning? Free Radic Biol Med 29: 927-945.

Haleagrahara N, Jackie T, Chakravarthi S, Kulur AB. (2011). Protective eff ect of alpha-lipoic acid against lead acetate-induced oxidative stress in the bone marrow of rats. Internat J Pharmacol 7: 217-227.

Heim KE, Tagliaferro AR, Bobliya DJ. (2002). Flavonoid antioxidants: chemistry, metabolism and structure activity relationships. J Nut Biochem 13: 572-584

Hsu PC, Guo YL. (2002). Antioxidant nutrients and lead toxicity. Toxicology 180: 33-44.

Hu P, Wang M, Chen WH, Liu J, Chen L, Yin ST, Yong W, Chen JT, Wang HL, Ruan DY. (2008). Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat dentate gyrus in vivo. Naunyn Schmiedebergs Arch Pharmacol 378: 43-51.

Hultberg B, Andersson A, Isaksson A. (2001). Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol. Toxicology 156: 93-100.

Hussin M, Hamid AA, Mohamad S, Saan N, Ismail M, Bejo MH. (2007). Protective eff ect of Centella asiatica extract and powder on oxidative stress in rats. Fd Chem 100: 535-541.

Jangid AP, John PJ, Yadav D, Mishra S, Sharma P. (2012). Impact of chronic lead exposure on selected biological markers. Indian J Clin Biochem 27: 83-89.

Kalia K, Flora SJ. (2005). Strategies for safe and eff ective therapeutic measures for chronic arsenic and lead poisoning. J Occup Health 47: 1-21.

Kilikdar D, Mukherjee D, Mitra E, Ghosh AK, Basu A, Chandra AM, Bandyoapdhyay D. (2011). Protective eff ect of aqueous garlic extract against lead-induced hepatic injury in rats. Indian J Exp Biol 49: 498-510.

Larson AJ, Symons JD, Jalili T. (2012). Therapeutic potential of quercetin to decrease blood pressure: review of effi cacy and mechanisms. Adv Nutr 3(1): 39-46.

Lidsky TI, Schneider JS. (2003). Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126: 5-19.

Liu CM, Ma JQ, Sun YZ. (2010). Quercetin protects the rat kidney against oxidative stress-mediated DNA damage and apoptosis induced by lead. Environ Toxicol Pharmacol 30: 264-271.

Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. (2007). Curcuminphospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 330: 155-163.

Mates JM. (2000). Eff ects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153: 83-104.

Mozafari MR, Flanagan J, Matia-Merino L, Awati A, Omri A, Suntres Z, Singh H. (2006). Recent trends in the lipid-based nanoencapsulation of antioxidants and their role in foods. J Sci Food Agric. 86: 2038-2045.

Mozafari MR, Johnson C, Hatziantoniou S, Demetzos C. (2008). Nanoliposomes and their applications in food nanotechnology. J Liposome Res. 18(4): 309-327

Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ. (2007). Lead exposure and cardiovascular disease--a systematic review. Environ Health Perspect 115: 472-482.

Needleman H. (2004). Lead poisoning. Annu Rev Med 55: 209-222.

Ng TB, Liu F, Wang ZT. (2000). Antioxidative activity of natural products from plants. Life Sci 66: 709-723.

Pande M, Flora SJ. (2002). Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats. Toxicology 177: 187-196.

Paramera EI, Konteles SJ, Karathanos VT. (2011). Stability and release properties of curcumin encapsulated in Saccharomyces cerevisiae, b-cyclodextrin and modifi ed starch. Fd Chem. 125: 913-922.

Patrick L. (2006) Lead toxicity part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern Med Rev 11: 114-127;.

Patrick L. (2006). Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev 11: 2-22.

Pearce JM. (2007). Burton’s line in lead poisoning. European neurology 57: 118-9

Pietta PG. (2000). Flavonoids as antioxidants. J Nat Prod 63: 1035-1042.

Piomelli S. (2002). Childhood lead poisoning. Pediatr Clin North Am 49: 1285-1304.

Ponnusamy K, Mohan M, Nagaraja HS. (2008). Protective antioxidant effect of Centella asiatica biofl avonoids on lead acetate induced neurotoxicity. Med J Malaysia 63 Suppl A: 102.

Pourjafar M, Aghbolaghi PA, Shakhse-Niaie M. (2007). Eff ect of garlic along with lead acetate administration on lead burden of some tissues in mice. Pak J Biol Sci 10: 2772-2774.

Rao MV, Jhala DD, Patel Chettiar SS. (2008). Cytogenetic alteration induced by nickel and chromium in human blood cultures and its amelioration by curcumin. Int J Hum Genet. 8: 301-305.

Rastogi SK. (2008). Renal eff ects of environmental and occupational lead exposure. Indian J Occup Environ Med 12: 103-106.

Rendon-Ramirez A, Cerbon-Solorzano J, Maldonado-Vega M, Quintanar-Escorza MA, Calderon-Salinas JV. (2007).Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes. Toxicol In Vitro 21: 1121-1126;.

Renner R. (2010). Exposure on tap: Drinking water as an overlooked source of lead. Environ Health Perspect 118: A68-A74.

Rice-Evans C. (2001). Flavonoid antioxidants. Curr Med Chem 8: 797-807.

Sahu A, Kasoju N, Goswami P, Bora U. (2011). Encapsulation of curcumin in pluronic block copolymer micelles for drug delivery applications. J Biomater Appl 25 : 619-39

Sainath SB, Meena R, Supriya C, Reddy KP, Reddy PS. (2011). Protective role of Centella asiatica on lead-induced oxidative stress and suppressed reproductive health in male rats. Environ Toxicol Pharmacol 32: 146-154.

Sajitha GR, Jose R, Andrews A, Ajantha KG, Augustine P, Augusti KT. (2010). Garlic oil and vitamin E prevent the adverse eff ects of lead acetate and ethanol separately as well as in combination in the drinking water of rats. Indian J Clin Biochem 25: 280-288.

Saleh HA, El-Aziz GA, El-Fark MM, El-Gohary M. (2009).Eff ect of maternal lead exposure on craniofacial ossifi cation in rat fetuses and the role of antioxidant therapy. Anat Histol Embryol 38: 392-399.

Sanders T, Liu Y, Buchner V, Tchounwou PB. (2009). Neurotoxic eff ects and biomarkers of lead exposure: A Review. Res Environ Health 24: 15-45.

Saxena G, Flora SJ. (2006). Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers

and Centella asiatica in lead poisoned rats. J Pharm Pharmacol 58: 547-559.

Senapati SK, Dey S, Dwivedi SK, Swarup D. (2001). Eff ect of garlic (Allium sativum L.) extract on tissue lead level in rats. J Ethnopharmacol 76: 229-232.

Senapati SK, Dey S, Dwivedi SK, Patra RC, Swarup D. (2004). Eff ect of thiamine hydrochloride on lead induced lipid peroxidation in rat liver and kidney. Vet Hum Toxicol 42: 236-7.

Sethi P, Jyoti A, Hussain E, Sharma D. (2009). Curcumin attenuates aluminiuminduced functional neurotoxicity in rats. Pharmacol Biochem Behav 93: 31-39.

Shalan MG, Mostafa MS, Hassouna MM, El-Nabi S E, El-Refaie A. (2005). Amelioration of lead toxicity on rat liver with vitamin C and silymarin supplements. Toxicology 206: 1-15.

Shan G, Tang T, Zhang X. (2009). The protective eff ect of ascorbic acid and thiamine supplementation against damage caused by lead in the testes of mice. J Huazhong Univ Sci Technolog Med Sci 29: 68-72.

Sharma V, Sharma A, Kansal L. (2010). The eff ect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice. Fd Chem Toxicol 48: 928-936.

Shukla PK, Khanna VK, Khan MY, Srimal RC. (2003). Protective eff ect of curcumin against lead neurotoxicity in rat. Hum Exp Toxicol 22: 653-658.

Silbergeld EK, Sauk J, Somerman M, Todd A, McNeill F, Fowler B, Fontaine A, van Buren J. (1993). Lead in bone: storage site, exposure source, and target organ. Neurotoxicology 14: 225-236.

Singh P, Sankhla V. (2010). In situ protective eff ect of curcumin on cadmium chloride induced genotoxicity in bone marrow chromosomes of Swiss albino mice. J Cell Mol Biol 8: 57-64.

Sivaprasad R, Nagaraj M, Varalakshmi P. (2002). Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damage in rat kidney. Arch Toxicol 76: 437-441.

Sivaprasad R, Nagaraj M, Varalakshmi P. (2003). Combined effi cacies of lipoic acid and meso-2,3-dimercaptosuccinic acid on lead-induced erythrocyte membrane lipid peroxidation and antioxidant status in rats. Hum Exp Toxicol 22: 183-192.

Sivaprasad R, Nagaraj M, Varalakshmi P. (2004). Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. J Nutr Biochem 15: 18-23.

Suresh D, Manjunatha H, Srinivasan K. (2007). Eff ect of heat processing of spices on the concentrations of their bioactive principles: Turmeric (Curcuma longa), red pepper (Capsicum annuum) and black pepper (Piper nigrum). J Fd Composition Analysis 20: 346-351.

Tariq SA. (2007). Role of ascorbic acid in scavenging free radicals and lead toxicity from biosystems. Mol Biotechnol 37: 62-65.

Terao J. (2009). Dietary fl avonoids as antioxidants. Forum Nutr 61: 87-94.

Vaya J, Aviram M. (2000). Nutritional antioxidants mechanisms of action, analyses of activities and medical applications. Curr Med Chem-Immunol Endo Metabolic Agents 1: 99-117.

Vij AG. (2009). Hemopoietic, hemostatic and mutagenic eff ects of lead and possible prevention by zinc and vitamin C. Al Ameen J Med Sci 2: 27-36.

Wanasundara PKJPD, Shahidi F. (2005). Antioxidants: Science, Technology, and Applications. Bailey’s Industrial Oil and Fat Products: John Wiley & Sons, Inc. pp

Wang C, Liang J, Zhang C, Bi Y, Shi X, Shi Q. (2007). Eff ect of ascorbic acid and thiamine supplementation at diff erent concentrations on lead toxicity in liver. Ann Occup Hyg 51: 563-569.

Willcox JK, Ash SL, Catignani GL. (2004). Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr 44: 275-295.

Youdim KA, Spencer JP, Schroeter H, Rice-Evans C. (2002). Dietary flavonoids as potential neuroprotectants. Biol Chem 383(3-4): 503-519.

Zigoneanu IG, Astete CE, Sabliov CM. (2008). Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release. Nanotechnol. 19: 105606: 8p.

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