Methylmercury and Oxidative Stress

  • Shabnum Nabi


ROS (reactive oxygen species) are generally very small molecules and are highly reactive due to the presence of unpaired valence shell electrons. ROS form as a natural by-product of the normal oxygen metabolism and have important roles in cell signaling. These molecules are generated continuously during oxidative metabolism and consist of inorganic molecules, such as superoxide radical anion (O2 ), hydrogen peroxide (H2O2), hydroxyl radicals (OH), as well as organic molecules such as alkoxyl and peroxyl radicals (Schulz et al. 2000). Some evidences suggest that the disturbance in the balance between oxidative and reductive cell processes is involved in the pathogenesis of many neurodegenerative conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease. Other conditions such as autoimmune and inflammatory diseases, cancer, and diabetes mellitus also seemed to be related to this disturbance (Schulz et al. 2000).


Reactive Oxygen Species Amyotrophic Lateral Sclerosis MeHg Exposure Superoxide Radical Anion MeHg Toxicity 
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  1. Adachi T, Kunimoto M (2005) Acute cytotoxic effects of mercuric compounds in cultured astrocytes prepared from cerebral hemisphere and cerebellum of newborn rats. Biol Pharm Bull 28:2308–2311PubMedCrossRefGoogle Scholar
  2. Ali SF, LeBel CP, Bondy SC (1992) Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13:637–648PubMedGoogle Scholar
  3. Aschner M, Syversen T, Souza DO, Rocha JBT, Farina M (2007) Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Braz J Med Biol Res 40:285–291PubMedCrossRefGoogle Scholar
  4. Castoldi AF, Barni S, Turin I, Gandini C, Manzo L (2000) Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury. J Neurosci Res 59:775–787PubMedCrossRefGoogle Scholar
  5. Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH (2006) Methylmercury induces pancreatic beta-cell apoptosis and dysfunction. Chem Res Toxicol 19:1080–1085PubMedCrossRefGoogle Scholar
  6. Clarkson TW (1997) The toxicity of mercury. Crit Rev Clin Lab Sci 34:369–403PubMedCrossRefGoogle Scholar
  7. Clarkson RW (2002) The three modern faces of mercury. Environ Health Perspect 110:11–23PubMedCentralPubMedCrossRefGoogle Scholar
  8. De Melo Reis RA, Herculano AM, da Silva MC, dos Santos RM, de Nascimento JL (2007) In vitro toxicity induced by methylmercury on sympathetic neurons is reverted by L-cysteine or glutathione. Neurosci Res 58:278–284PubMedCrossRefGoogle Scholar
  9. Do Nascimento JLM, Oliveira KRM, Crespo-Lopez ME, Macchi BM, Maues LAL, Pinheiro MCN, Silveira LCL, Herculano AM (2008) Methylmercury neurotoxicity and antioxidant defenses. Indian J Med Res 128:373–382PubMedGoogle Scholar
  10. Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62:649–671PubMedCrossRefGoogle Scholar
  11. Gasso S, Cristofol RM, Selema G, Rosa R, Rodriguez-Farre E, Sanfeliu C (2001) Antioxidant compounds and Ca2 + pathway blockers differentially protect against methylmercury and mercuric chloride neurotoxicity. J Neurosci Res 66:135–145PubMedCrossRefGoogle Scholar
  12. International Medical Veritas Association (IMVA) (2006) Diabetes and mercury poisoning. Medical NewsGoogle Scholar
  13. Kaur P, Aschner M, Syversen T (2007) Role of glutathione in determining the differential sensitivity between the cortical and cerebellar regions towards mercury-induced oxidative stress. Toxicology 230:164–177PubMedCrossRefGoogle Scholar
  14. Khanna S, Roy S, Parinandi NL, Maurer M, Sen CK (2006) Characterization of the potent neuroprotective properties of the natural vitamin E alphatocotrienol. J Neurochem 98:1474–1486PubMedCentralPubMedCrossRefGoogle Scholar
  15. Kunimoto M (1994) Methylmercury induces apoptosis of rat cerebellar neurons in primary culture. Biochem Biophys Res Commun 204:310–317PubMedCrossRefGoogle Scholar
  16. Lee YW, Ha MS, Kim YK (2001) Role of reactive oxygen species and glutathione in inorganic mercury-induced injury in human glioma cells. Neurochem Res 26:1187–1193PubMedCrossRefGoogle Scholar
  17. Miura K, Himeno S, Koide N, Imura N (2000) Effects of methylmercury and inorganic mercury on the growth of nerve fibers in cultured chick dorsal root ganglia. Tohoku J Exp Med 192:195–210PubMedCrossRefGoogle Scholar
  18. Mullaney KJ, Fehm MN, Vitarella D, Wagoner DE, Aschner M (1994) The role of -SH groups in methyl mercuric chloride-induced D-aspartate and rubidium release from rat primary astrocyte cultures. Brain Res 641:1–9PubMedCrossRefGoogle Scholar
  19. National Research Council (2000) Toxicological effects of methylmercury. National Academy Press, Washington, DC, Committee on the Toxicological Effects of MethylmercuryGoogle Scholar
  20. Olivieri G, Brack C, Muller-Spahn F, Stahelin HB, Herrmann M, Renard P, Brockhaus M, Hock C (2000) Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells. J Neurochem 74:231–236PubMedCrossRefGoogle Scholar
  21. Osakada F, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A (2004) Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons. Neuropharmacology 47:904–915PubMedCrossRefGoogle Scholar
  22. Park ST, Lim KT, Chung YT, Kim SU (1996) Methylmercury induced neurotoxicity in cerebral neuron culture is blocked by antioxidants and NMDA receptor antagonists. Neurotoxicology 17:37–45PubMedGoogle Scholar
  23. Pinheiro MCM, Crespo-Lopez ME, Vieira JLF, Oikawa T, Guimaraes GA, Araujo CC, Amoras WW, Ribeiro DR, Herculano AM, do Nascimento JLM, Silveira LCL (2007) Mercury pollution and childhood in Amazon riverside villages. Environ Int 33:56–61PubMedCrossRefGoogle Scholar
  24. Ricciarelli R, Zingg JM, Azzi A (2001) Vitamin E: protective role of a Janus molecule. FASEB J 15:2314–2325PubMedCrossRefGoogle Scholar
  25. Sarafian TA (1999) Methylmercury-induced generation of free radical: biological implications. Met Ions Biol Syst 36:415–444PubMedGoogle Scholar
  26. Sarafian T, Verity MA (1990) Altered patterns of protein phosphorylation and synthesis caused by methylmercury in cerebellar granule cell culture. J Neurochem 55:922–929PubMedCrossRefGoogle Scholar
  27. Sarafian TA, Vartavarian L, Kane DJ, Bredesen DE, Verity MA (1994) Bcl-2 expression decreases methyl mercury-induced free radical generation and cell killing in a neural cell line. Toxicol Lett 74:149–155PubMedCrossRefGoogle Scholar
  28. Schulz JB, Lindenau J, Seyfried J, Dichgans J (2000) Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 267:4904–4911PubMedCrossRefGoogle Scholar
  29. Shanker G, Aschner A (2003) Methylmercury-induced reactive oxygen species formation in neonatal cerebral astrocytic cultures is attenuated by antioxidants. Mol Brain Res 110:85–91PubMedCrossRefGoogle Scholar
  30. Shanker G, Mutkus LA, Walker SJ, Aschner M (2002) Methylmercury enhances arachidonic acid release and cytosolic phospholipase A2 expression in primary cultures of neonatal astrocytes. Brain Res Mol Brain Res 106:1–11PubMedCrossRefGoogle Scholar
  31. Shanker G, Syversen T, Aschner JL, Aschner M (2005) Modulatory effect of glutathione status and antioxidants on methylmercury induced free radical formation in primary cultures of cerebral astrocytes. Mol Brain Res 37:11–22CrossRefGoogle Scholar
  32. Shichiri M, Takanezawa Y, Uchida K, Tamai H, Arai H (2007) Protection of cerebellar granule cells by tocopherols and tocotrienols against methylmercury toxicity. Brain Res 1182:106–115PubMedCrossRefGoogle Scholar
  33. Soderstrom S, Ebendal T (1995) In vitro toxicity of methyl mercury: effects on nerve growth factor (NGF)-responsive neurons and on NGF synthesis in fibroblasts. Toxicol Lett 75:133–144PubMedCrossRefGoogle Scholar
  34. Sorg O, Schilter B, Honegger P, Monnet-Tschudi F (1998) Increased vulnerability of neurones and glial cells to low concentrations of methylmercury in a prooxidant situation. Acta Neuropathol 96:621–627PubMedCrossRefGoogle Scholar
  35. Usuki F, Yasutake A, Umehara F, Tokunaga H, Matsumoto M, Eto K, Ishiura S, Higuchi I (2001) In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat. Neurosci Lett 304:199–203PubMedCrossRefGoogle Scholar
  36. Verity MA, Brown WJ, Cheung M, Czer G (1977) Methylmercury inhibition of synaptosomes and brain slice protein synthesis. In vivo and in vitro studies. J Neurochem 29:673–679PubMedCrossRefGoogle Scholar
  37. Yee S, Choi BH (1996) Oxidative stress in neurotoxic effects of methylmercury poisoning. Neurotoxicology 17:17–26PubMedGoogle Scholar
  38. Yoshino Y, Mozai T, Nakao K (1966) Distribution of mercury in the brain and its subcellular units in experimental organic mercury poisoning. J Neurochem 13:397–406CrossRefGoogle Scholar

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© Springer India 2014

Authors and Affiliations

  • Shabnum Nabi
    • 1
  1. 1.Interdisciplinary Brain Research Centre (IBRC) Jawaharlal Nehru Medical CollegeAligarh Muslim UniversityAligarhIndia

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