Skip to main content
Log in

Co-administration of α-Lipoic Acid and Vitamin C Protects Liver and Brain Oxidative Stress in Mice Exposed to Arsenic Contaminated Water

  • Published:
Water Quality, Exposure and Health Aims and scope Submit manuscript

Abstract

Arsenic is one of the most hazardous substances in the environment known to cause toxicity in multiple organs via generation of oxidative stress. The molecular basis for arsenic toxicity involves direct or indirect damage to protein, lipid and DNA. Several studies have focused on possible toxic effects on membrane components and have identified a correlation between these effects of arsenic-induced oxidative damage. This study was aimed to evaluate arsenic-induced oxidative stress in the liver and brain following chronic exposure in mouse and also the protective efficacy of co-administrating with two naturally occurring antioxidants (α-lipoic acid and vitamin C) either individually or in combination. Thirty male mice were exposed to sodium arsenite (50 ppm) alone, as well as to α-lipoic acid (10 mg/kg) and vitamin C either alone or in combination. We observed a significant increase in lipid peroxidation, intracellular calcium, reactive oxygen species (ROS) and caspase activity, while there was a significant decrease in antioxidant enzymes and ATPase activity on arsenite exposure in mice. These alterations were marginally restored by co-administration of vitamin C and α-lipoid acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in mice. The results indicate that arsenite-induced oxidative stress can be significantly protected by co-administration of α-lipoic acid and vitamin C individually, but the best effects could be observed with combined administration of two antioxidants during arsenite exposure in animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aebi H (1984) Catalase. In: Packer L (ed) Methods in enzymol. Academic Press, Orlando, pp 125–126

    Google Scholar 

  • Ashidate K, Kawamura M, Tohda H (2003) Ascorbic acid augments cytotoxicity induced by oxidized low-density lipoprotein. J Atheroscler Thromb 10:7–12

    CAS  Google Scholar 

  • Bast A, Haenen GR (2003) Lipoic acid: a multifunctional antioxidant. Biofactors 17:207–213

    Article  CAS  Google Scholar 

  • Berlin A, Schaller KH (1974) European standardized method for the determination of delta aminolevulinic acid dehydratase activity in blood. Z Clin Chem Clin Biochem 12:389–390

    CAS  Google Scholar 

  • Bhadauria S, Flora SJS (2007) Response of arsenic-induced oxidative stress, DNA damage and metal imbalance to combined administration of DMSA and monoisoamyl DMSA during chronic arsenic poisoning in rats. Cell Biol Toxicol 23:91–104

    Article  CAS  Google Scholar 

  • Burton GW, Ingold KU (1986) Vitamin E: application of principles of physical organic chemistry to the exploration of its structure and function. Acc Chem Res 19:194–201

    Article  CAS  Google Scholar 

  • Chen Y, Santella RM, Kibriya MG, Wang Q, Kappil M, Wendy JV, Joseph HG, Ahsan H (2007) Association between arsenic exposure from drinking water and plasma levels of soluble cell adhesion molecules. Environ Health Perspect 115:1415–1420

    CAS  Google Scholar 

  • Cremer DR, Rabeler R, Roberts A, Lynch B (2006) Long-term safety of alpha-lipoic acid (ALA) consumption: a 2-year study. Long Regul Toxicol Pharmacol 46:193–201

    Article  CAS  Google Scholar 

  • Dawson EB, Harris WA (1997) Effect of ascorbic acid supplementation on blood lead levels. J Am Coll Nutr 16:480

    Google Scholar 

  • Del Razo LM, Quintanilla-Vega B, Brambila-Colombres E, Calderon-Aranda ES, Manno M, Albores A (2001) Stress proteins induced by arsenic. Toxicol Appl Pharmacol 177:132–148

    Article  CAS  Google Scholar 

  • Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphates. J Biol Chem 66:375–379

    CAS  Google Scholar 

  • Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  CAS  Google Scholar 

  • Flora SJS (1999) Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol 26:865–869

    Article  CAS  Google Scholar 

  • Flora SJS (2002) Lead in the environment: prevention and treatment. J Environ Biol 23:29–44

    Google Scholar 

  • Flora SJS, Bhadauria S, Dhaked RK, Pant SC (2005) Arsenic-induced blood and brain oxidative stress and its response to some thiol chelators in male rats. Life Sci 77:2324–2337

    Article  CAS  Google Scholar 

  • Flora SJS, Bhadauria S, Kannan GM, Singh N (2007) Arsenic-induced oxidative stress and the role of antioxidant supplementation during chelation: a review. J Environ Biol 28:333–347

    CAS  Google Scholar 

  • Flora SJS, Mehta A, Gupta R (2009) Prevention of arsenic-induced hepatic apoptosis by concomitant administration of garlic extracts in mice. Chem Biol Interac 177:227–233

    Article  CAS  Google Scholar 

  • Gonzalez-Pereza O, Gonzalez-Castanedab RE (2006) Therapeutic perspectives on the combination of a-lipoic acid and vitamin E. Nutr Res 26:1–5

    Article  CAS  Google Scholar 

  • Goyer RA, Cherian MG (1979) Ascorbic acid and EDTA treatment of lead toxicity in rats. Life Sci 24:433–438

    Article  CAS  Google Scholar 

  • Grad JM, Bahlis NJ, Reis I, Oshiro MM, Dalton WS, Boise LH (2001) Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood 98:805–813

    Article  CAS  Google Scholar 

  • Guha Mazumder DN, Ghosal UC, Saha J, Santra A, De BK, Chatterjee A, Dutta S, Angle CR, Ceteno JA (1998) Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arsenic contaminated subsoil water. Clin Toxicol 36:683–690

    Article  CAS  Google Scholar 

  • Gurer H, Ercal N (2000) Can antioxidants be beneficial in the treatment of lead poisoning? Free Rad Biol Med 29:927–945

    Article  CAS  Google Scholar 

  • Gurer H, Neal R, Yang P, Oztezcan S, Ercal N (1999) Captopril as an antioxidant in lead-exposed Fischer 344 rats. Hum Exp Toxicol 18:27–32

    Article  CAS  Google Scholar 

  • Gutteridge JMC, Quinlan GJ (1983) Malondialdehyde formation from lipid peroxides in thiobarbituric acid test: the role of lipid radicals, iron salts, metal chelators. J Appl Biochem 5:293–299

    CAS  Google Scholar 

  • Halliwell B (1984) Oxygen radicals: a common sense look at their nature and medical importance. Med Biol 62:71–77

    CAS  Google Scholar 

  • Halliwell B (1994) Free radicals and antioxidants: a personal view. Nutr Rev 52:253–265

    CAS  Google Scholar 

  • Halliwell B (2002) Effect of diet on cancer development: is oxidative DNA damage a biomarker? Free Radic Biol Med 32:968–974

    Article  CAS  Google Scholar 

  • Hissin PJ, Hilf R (1976) A fluorometric method for the determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–216

    Article  CAS  Google Scholar 

  • Hughes MF (2002) Arsenic toxicity and potential mechanism of action. Toxicol Lett 133:1–16

    Article  CAS  Google Scholar 

  • Jollow DJ, Mitchell JR, Zamppaglione Z, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolites. Pharmacology 11:151–169

    Article  CAS  Google Scholar 

  • Kagan VE, Shvedova A, Serbinova E (1992) Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol 44:1637–1649

    Article  CAS  Google Scholar 

  • Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    CAS  Google Scholar 

  • Kalia K, Flora SJS (2005) Strategies for safe and effective treatment for chronic arsenic and lead poisoning. J Occup Health 47:1–21

    Article  CAS  Google Scholar 

  • Kannan GM, Flora SJS (2004) Chronic arsenic poisoning in rats: treatment with combined administration of succimers and an antioxidant. Ecotoxicol Environ Saf 58:37–43

    Article  CAS  Google Scholar 

  • Karasavvas N, Carcamo JM, Stratis G, Golde DW (2005) Vitamin C protects HL60 and U266 cells from arsenic toxicity. Blood 105:4004–4012

    Article  CAS  Google Scholar 

  • Kitchin KT (2001) Recent advances in arsenic carcinogenesis: mode of action, animal model system and methylated arsenic metabolites. Toxicol Appl Pharmacol 172:249–261

    Article  CAS  Google Scholar 

  • Lindberg AL, Rahman M, Persson LA, Vahter M (2008) The risk of arsenic-induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure. Toxicol Appl Pharmacol 230:9–16

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  • Mehta A, Flora SJS (2001) Possible role of metal redistribution, hepatotoxicity and oxidative stress in chelating agents induced hepatic and renal metallothione in rats. Food Chem Toxicol 39:1029–1038

    Article  CAS  Google Scholar 

  • Mishra D, Mehta A, Flora SJS (2008) Reversal of hepatic apoptosis with combined administration of DMSA and its analogues in guinea pigs: role of glutathione and linked enzymes. Chem Res Toxicol 21:400–407

    Article  CAS  Google Scholar 

  • Mittal M, Flora SJS (2006) Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice. Chem Biol Interact 162:128–139

    Article  CAS  Google Scholar 

  • Navari-izzo F, Quartacci MF, Sgherri C (2002) Lipoic acid: a unique antioxidants in the detoxification of activated oxygen species. Plant Physiol Biochem 40:463–470

    Article  CAS  Google Scholar 

  • Nordenson I, Beckman L (1991) Is genotoxic effect of arsenic mediated by oxygen free radicals? Hum Hered 41:71–73

    Article  CAS  Google Scholar 

  • NRC (National Research Council) (2001) Arsenic in drinking water. National Academy Press, Washington

    Google Scholar 

  • Ohkawa H, Onishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  • Ou P, Tritschler HJ, Wolff SP (1995) Thioctic acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol 50:123–126

    Article  CAS  Google Scholar 

  • Packer L, Witt EH, Tritschler HJ (1995) α-Lipoic acid as a biological antioxidant. Free Radic Biol Med 19:227–250

    Article  CAS  Google Scholar 

  • Pandey PK, Sharma R, Roy M, Roy S, Pandey M (2006) Arsenic contamination in the Kanker district of central-east India: geology and health effects. Environ Geochem Health 28:409–420

    Article  CAS  Google Scholar 

  • Rabbani GH, Saha SK, Akhtar M, Marni F, Mitra AK, Ahmed S, Alauddin M, Bhattacharjee M, Sultana S, Chowdhury AK (2003) Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: preliminary results. J Environ Sci Health A Tox Hazard Subst Environ Eng 38:273–287

    Google Scholar 

  • Rana SVS, Allen T, Singh R (2002) Inevitable glutathione, then and now. Ind J Exp Biol 40:706–716

    CAS  Google Scholar 

  • Ribiere C, Hininger I, Rouach H, Nordmann R (1992) Effects of chronic ethanol administration on free radical defense in rat myocardium. Biochem Pharmacol 44:1495–1500

    Article  CAS  Google Scholar 

  • Seaton TA, Jenner P, Marsden CD (1996) The isomers of thioctic acid alter 14C-deoxyglucose incorporation in rat basal ganglia. Biochem Pharmacol 51:983–986

    Article  CAS  Google Scholar 

  • Seth PK, Tangari KK (1966) Biochemical effects of some newer salicylic acid congeners. J Pharm Pharmacol 18:831–833

    CAS  Google Scholar 

  • Shila S, Subathra M, Muthuswamy AD, Chinnakkannu P (2005) Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-α-lipoic acid. Arch Toxicol 79:140–146

    Article  CAS  Google Scholar 

  • Sigel H, Prijs B, McCormick DB, Shih JCH (1978) Stability of binary and ternary complexes of α-lipoate and lipoate derivatives with Mn2+, Cu2+ and Zn2+ in solution. Arch Biochem Biophys 187:208–214

    Article  CAS  Google Scholar 

  • Smith AH, Lingas EO, Rahman M (2000) Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ 78:1093–1103

    CAS  Google Scholar 

  • Socci DJ, Bjugstad KB, Jones HC, Pattisapu JV, Arendash GW (1999) Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Exp Neurol 155:109–118

    Article  CAS  Google Scholar 

  • Tajmir-Riahi HA (1991) Coordination chemistry of vitamin C. Part II Interaction of L-ascorbic acid with Zn(II), Cd(II), Hg(II), and Mn(II) ions in the solid state and in aqueous solution. J Inorg Biochem 42:47–55

    Article  CAS  Google Scholar 

  • Thomas DJ, Styblo M, Lin S (2001) The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol 176:127–144

    Article  CAS  Google Scholar 

  • Tripathi N, Kannan GM, Pant BP, Jaiswal DK, Malhotra PR, Flora SJS (1997) Arsenic-induced changes in certain neurotransmitters levels and their recoveries following chelation in rat whole brain. Toxicol Lett 92:201–208

    Article  CAS  Google Scholar 

  • Yamanaka K, Hasegawa A, Sawamura R, Okada S (1991) Cellular response to oxidative damage in lung induces by administration of dimethylarsinic acid, a major metabolite of inorganic arsenic in mice. Toxicol Appl Pharmacol 108:205–213

    Article  CAS  Google Scholar 

  • Zablotska LB, Chen Y, Graziano JH, Parvez F, Van Geen A, Howe GR, Ahsan H (2008) Protective effects of B vitamins and antioxidants on the risk of arsenic-related skin lesions in Bangladesh. Environ Health Perspect 116:1056–1062

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Swaran J. S. Flora.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaur, H., Mishra, D., Bhatnagar, P. et al. Co-administration of α-Lipoic Acid and Vitamin C Protects Liver and Brain Oxidative Stress in Mice Exposed to Arsenic Contaminated Water. Water Expo. Health 1, 135–144 (2009). https://doi.org/10.1007/s12403-009-0013-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12403-009-0013-8

Keywords

Navigation