Abstract
Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.
Similar content being viewed by others
References
Anner BM, Moosmayer M, Imesch E (1992) Mercury blocks Na-K-ATPase by a ligand-dependent and reversible mechanism. Am J Physiol 262:F830–F836
Aremu DA, Madejczyk MS, Ballatori N (2008) N-acetyl cysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Env Health Perspect 116:26–31
Baginski ES, Foa PP, Zak B (1974) Glucose-6-phosphate. In: Bergmeyer (ed) Methods in Enzymatic Analysis, 2nd edn. Verlag Chemie Weinhiem, Academy Press, New York, pp 876–880
Ballatori N, Lieberman MW, Wang W (1998) N-acetyl cysteine as an antidote in methylmercury poisoning. Env Health Perspect 106:267–271
Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK, Singh K et al (2008) Hepatoprotective activity of Woodfordia fruticosa Kurz flowers against carbon tetrachloride induced hepatotoxicity. J Ethnopharmacol 119:218–224
Chen RW, Whanger PD, Weswig PH (1975) Selenium induced redistribution of Cd binding to tissue proteins: a possible mechanism of protection against Cd toxicity. Bioinorg Chem 4:125–133
Cochin J, Axelrod J (1959) Biochemical pharmacological changes in the rats following chronic administration of morphine nalorphine and normorphine. J Pharmacol Exp Ther 125:105–110
de Ceballos ML, Brera B, Fernandez-Tome MP (2001) Beta-Amyloid-induced cytotoxicity, peroxide generation and blockade of glutamate uptake in cultured astrocytes. Clin Chem Lab Med 39:317–318
El-Demerdash FM (2004) Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol 18:113–121
Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphatase. J Biol Chem 66:375–400
Fukino H, Hirai M, Hsuch Y, Yamane Y (1984) Effect of zinc pretreatment on mercuric chloride induced lipid peroxidation in the rat kidney. Toxicol Appl Pharmacol 73:395–401
Ganther HE (1973) Modification of methylmercury toxicity and metabolism by selenium and vitamin E: Possible mechanisms. Environ Health Perspect 25:71–76
Giradi E, Elias M (1993) Effect of different glutathione levels on renal mercury deposition and excretion in the rat. Toxicology 81:57–67
Goepter AR, Scheerens H, Vermeulen NPE (1995) Oxygen and xenobiotics reductase activities in cytochrome P450. Clin Rev Toxicol 25:59–84
Johri S, Shukla S, Sharma P (2002) Role of antioxidant and chelating agent against beryllium induced toxicity. Indian J Exp Biol 40:575–582
Joshi D, Mittal D, Nirala SK, Bhadauria M, Shrivastava S, Shukla S (2010a) Role of micronutrients against dimethylmercury intoxication in male rats. Env Toxicol Pharmacol 29:97–103
Joshi D, Mittal D, Shrivastava S, Shukla S (2010b) Protective role of thiol chelators against dimethylmercury induced toxicity in male rats. Bull Env Contam Toxicol 84:613–617
Joshi D, Mittal D, Shukla S, Shrivastava AK (2010c) Therapeutic potential of N-acetyl cysteine with antioxidants (Zn and Se) supplementation against dimethylmercury toxicity in male albino rats. Exp Toxicol Pathol. doi: 10.1016/j.etp.2010.07.001
Kalia K, Flora SJS (2005) Strategies for safe and effective treatment for chronic arsenic and lead poisoning. J Occup Health 47:1–21
Kato R, Gillette JR (1965) Effect of starvation on NADPH dependent enzymes in liver microsomes of male and female rats. J Pharmacol Exp Ther 150:279–284
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin’s phenol reagent. J Biol Chem 193:265–275
Miquel J (2002) Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann NY Acad Sci 959:508–516
Naidu KA, Ramamurthi R (2001) Acute effect of mercury toxicity on some enzymes in liver of teleost Sarotherodon mossambicus. Ecotoxicol Env Saf 8:215–218
Neri BP, Frings CS (1973) Improved method for determination for triglycerides in serum. Clin Chem 19:1201–1202
Nirala SK, Bhadauria M, Shukla S, Agrawal OP, Mathur A, Li QP et al (2008) Pharmacological intervention of tiferron and propolis to alleviate beryllium-induced hepatorenal toxicity. Fundam Clin Pharmacol 22:403–415
Novikoff AB (1961) The cell. In: Brachet J, Mirsky AE (eds) Lysosomes and related particles, 2nd edn. Academic, New York, pp 423–488
Peixoto NC, Serafim MA, Flores EMM, Bebianno MJ, Pereira ME (2007) Metallothionein, zinc, and mercury levels in tissues of young rats exposed to zinc and subsequently to mercury. Life Sci 81:1264–1271
Reitman S, Frankel SA (1957) A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63
Riley V (1960) Adaptation of orbital bleeding technique to rapid serial blood studies. Proc Soc Exp Biol Med 104:751–753
Sastry KV, Sharma K (2005) Effects of mercuric chloride on the activities of brain enzymes in a fresh water teleost, Ophiocephalus (Channa) punctatus. Arch Environ Contam Toxicol 9:425–430
Schenkman JB, Cinti DL (1978) Preparation of microsomes from calcium. Methods Enzymol 52:83–89
Sharma SK, Krishna Murti CR (1968) Production of lipid peroxides of brain. J Neurochem 15:147–149
Shukla S, Singh V, Joshi D (2007) Modulation of toxic effects of organic mercury by different antioxidants. Toxicol Intern 14:67–71
Singh V, Joshi D, Shrivastava S, Shukla S (2007) Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat. Indian J Exp Biol 45:1037–1044
Slater EC, Bonner WD (1952) The effect of fluoride on the succinic oxidase system. Biochem J 82:185–191
Snedecor GW, Cochran WG (1994) Statistical method, 8th edn. Iowa State University Press, Ames, pp 217–236
Stefanidou M, Maravelias C, Dona A, Spiliopoulou C (2006) Zinc: a multipurpose trace element. Arch Toxicol 80:1–9
Studer R, Baysang G, Brack C (2001) N-acetyl-L-cystein downregulates beta-amyloid precursor protein gene transcription in human neuroblastoma cells. Biogerontology 2:55–60
Subramanian L, Selvam R (1999) Prevention of CCl4 induced hepatotoxicity by aqueous extract of Turmeric. Nutr Res 19:429–441
United States Air Force (USAF) (1990) The installation restoration program toxicology guide. Harry G. Armstrong Aerospace Medical Research Laboratory, Wright-Patterson AFB, Ohio, pp 73-1–73-84
Verity MA, Reith A (1967) Effect of mercurial compounds on the structure-linked latency of lysosomal hydrolases. Biochem J 105:685–690
Woods AE, Ellis RC (1994) Laboratory histopathology: a complete reference. Churchill Livingstone, Edinburgh
Wroblewski F, La Due JS (1955) Colorimetric method for LDH. In: Wootton IDP (ed) Microanalysis in medical biochemistry, 4th edn. Churchill Livingstone, London
Yang DY, Chen YW, Gunn JM, Belzile N (2008) Selenium and mercury in organisms: interactions and mechanisms. Env Rev 16:71–92
Zhao P, Kalhorn TF, Slattery JT (2002) Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. Hepatology 36:326–335
Zlatkis A, Zak B, Boyle AJ (1953) A new method for direct determination of serum cholesterol. J Lab Clin Med 41:486–492
Acknowledgments
D. Joshi is grateful to the Jiwaji University, Gwalior, (M. P.) for Scholarship (F/DEV/2007/1277) 2004–2006. The authors thank to R. Mathur, School of Studies in Zoology, Jiwaji University, Gwalior, for invaluable suggestions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Joshi, D., Mittal, D., Shrivastav, S. et al. Combined Effect of N-Acetyl Cysteine, Zinc, and Selenium Against Chronic Dimethylmercury-Induced Oxidative Stress: A Biochemical and Histopathological Approach. Arch Environ Contam Toxicol 61, 558–567 (2011). https://doi.org/10.1007/s00244-011-9656-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00244-011-9656-0