Samir A. Bashandy
Department of Zoology, College of Science, King Saud University,
P.O. Box 2455, Riyadh 11451, Saudi Arabia
I. M. Alhazza
Department of Zoology, College of Science, King Saud University,
P.O. Box 2455, Riyadh 11451, Saudi Arabia
Mohammad Mubarak
Department of Zoology, College of Science, King Saud University,
P.O. Box 2455, Riyadh 11451, Saudi Arabia
ABSTRACT
The influence of Zinc (Zn) on Cadmium (Cd) intoxication was investigated in male rats. The exposure of the rats to Cd (2.2 mg kg-1 CdCl2, injected subcutaneously 4 times weekly for 2 months) caused alterations in ultrastructure of liver as manifested by deterioration of mitochondrial cristae, deposition of large amount of collagen fibrils and a hypertrophy of Kupffer cells accompanied by presence of large sized lipid droplets in their cytoplasm. On the other hand, the blood hydroperoxide level, concentrations of Zn, Cd and reduced Glutathione (GSH) in the liver were increased during the treatment period with Cd. On the other hand, blood GSH level and hepatic catalase activity decreased in the rats injected with Cd. Moreover, treatment with Cd produced significant increases in plasma Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), gamma Glutamyl Transferase (γ GT) and alkaline phosphatase activities and bilirubin concentration. Administration of Zn (2.2 mg kg-1 ZnCl2 injected s.c. 4 times weekly for 2 months) one hour prior to cadmium exposure ameliorated the toxic effects of Cd. Zn alleviated the elevation of hydroperoxide level, alterations in ultrastructure of liver and hepatic enzymes and Cd accumulation induced by Cd. We conclude that Zn could serve as a physiological antioxidant against cadmium-mediated oxidative stress.
PDF References Citation
How to cite this article
Samir A. Bashandy, I. M. Alhazza and Mohammad Mubarak, 2006. Role of Zinc in the Protection Against Cadmium Induced Hepatotoxicity. International Journal of Pharmacology, 2: 79-88.
DOI: 10.3923/ijp.2006.79.88
URL: https://scialert.net/abstract/?doi=ijp.2006.79.88
DOI: 10.3923/ijp.2006.79.88
URL: https://scialert.net/abstract/?doi=ijp.2006.79.88
REFERENCES
- Wennberg, A., 1994. Neurotoxic effects of selected metals. Scand. J. Work Environ. Health, 20: 65-71.
Direct Link - Gunnarsson, D., G. Nordberg, P. Lundgren and G. Selstam, 2003. Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats. Toxicology, 183: 57-63.
CrossRefDirect Link - Stohs, S.J., D. Bagchi, E. Hassoun and M. Bagchi, 2000. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J. Environ. Pathol. Toxicol. Oncol., 19: 201-213.
PubMed - Hussain, T., G.S. Shukla and S.V. Chandra, 1987. Effects of cadmium on superoxide dismutase and lipid peroxidation in liver and kidney of growing rats: In vivo and in vitro studies. Pharmacol. Toxicol., 60: 355-358.
CrossRefDirect Link - Yu, R.A. and X.M. Chen, 2004. Effect of selenium on rat hepatocellular DNA damage induced by cadmium in vitro. Chinese J. Prevent. Med., 38: 29-32.
Direct Link - Dudley, R.E., D.J. Svoboda and C.D. Klaassen, 1982. Acute exposure to cadmium causes severe liver injury in rats. Toxicol. Applied Pharmacol., 65: 302-313.
CrossRefPubMedDirect Link - Tzirogiannis, K.N., G.L. Panoutsopoulos, M.D. Demonakou, G.K. Papadimas and V.G. Kondyli et al., 2004. The hepatoprotective effect of putrescine against cadmium induced acute liver injury. Arch. Toxicol., 78: 321-329.
Direct Link - Lemarie, A., D. Lagadic-Gossmann, C. Morzadec, N. Allain, O. Fardel and L. Verchet, 2004. Cadmium induces caspase-independent apoptosis in liver HEP3B cells: Role for calcium in signaling oxidative stress-related impairment of mitochondria and relocation of endonuclease G and apoptosis-inducing factor. Free Radic. Biol. Med., 36: 1517-1531.
Direct Link - Qu, W., J. Liu, R. Fuquay, R. Shimoda, T. Sakurai, J.E. Saavedra, L.K. Keefer and M.P. Waalkes, 2005. The nitric oxide prodrug, V-PYRRO/NO, protects against cadmium toxicity and apoptosis at the cellular level. Nitric Oxide, 12: 114-120.
Direct Link - Prasad, A.S., B. Babo, W.J. Frances, B.O. Kucuk and F.H. Sarkar, 2004. Antioxidant effect of zinc in humans. Free Radic. Biol. Med., 37: 1182-1190.
Direct Link - Li, J., J. Yi, C. Wang and P. Xu, 2000. Effect of cadmium on apoptosis of spermatogenic cells in rat testis and the protection eaffect of zinc against it. Wei Sheng Yan Jiu, 29: 135-137.
Direct Link - Moustafa, S.A., 2004. Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats. Toxicol. Applied Pharmacol., 201: 149-155.
Direct Link - Brocardo, P.S., P. Pandolfo, R.N. Takahashi, A.S. Rodrigues and A. Dafre, 2005. Antioxidant defences and lipid peroxidation in the cerebral cortex and hippocampus following acute exposure to malathione and/or zinc chloride. Toxicology, 207: 283-291.
Direct Link - Rudolf, E., M. Cervinka and J. Cerman, 2005. Zinc has ambiguous effects on chromium induced oxidative stress and apoptosis. J. Trace Elem. Med. Biol., 18: 251-260.
Direct Link - Yousef, M.I., H.A. El Hendy, F.M. EI-Demerdash and E.I. Elagamy, 2002. Dietary zinc deficiency induced changes in the activity and levels of free radicals, lipids and protein electrophoretic behavior in growing rats. Toxicology, 175: 223-234.
Direct Link - Virgili, F., R. Canal, F. Figus, F. Nobili and E. Mengheri, 1999. Intestinal damage induced by Zn deficiency is associated with enhanced SOD activity in rats. Free Radic. Biol. Med., 26: 1194-1201.
Direct Link - Aebi, H., 1984. Catalase in vitro. In: Methods in Enzymology, Packer, L., Academic Press, Cambridge, Massachusetts, United States, ISBN: 9780121820053, pp: 121-126.
CrossRefDirect Link - Beutler, E., O. Duron and B.M. Kelly, 1963. Improved method for the determination of blood glutathione. J. Lab. Clin. Med., 61: 882-888.
PubMedDirect Link - Anderson, M.E., 1985. Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol., 113: 548-555.
PubMedDirect Link - Dorta, D.J., S. Leite, K.C. de Marco, M.R. Prado and T. Rodrigues et al., 2003. A proposed sequence of events for cadmium induced mitochondrial impairment. J. Inorganic Biochem., 97: 251-257.
Direct Link - Nigam, D., G.S. Shukla and A.K. Agarwal, 1999. Glutathione depletion and oxidative damage in mitochondria following exposure to cadmium in rat liver and kidney. Toxicol. Lett., 106: 151-157.
CrossRefDirect Link - Harstad, E.B. and C.D. Klaassen, 2002. INOS-null mice are not resistant to cadmium chloride induced hepatotoxicity. Toxicology, 175: 83-90.
Direct Link - Weiss, S.J. and A.F. Lo Buglio, 1982. Phagocyte-enerated oxygen metabolites and cellular injury. Lab. Invest., 804: 154-160.
Direct Link - Stohs, S.J. and D. Bagchi, 1995. Oxidative mechanism in the toxicity of metal ions. Free Radic. Biol. Med., 18: 321-336.
PubMedDirect Link - Jurczuk, M., M.M. Brzoska, J. Moniuszko-Jakoniuk, M. Galazyn-Sidorczuk and E. Kulikowska-Karpinska, 2004. Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem. Toxicol., 42: 429-438.
CrossRefDirect Link - De Cavanagh, E.M., F. Inserra, L. Ferder and C.G. Fraga, 2000. Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. Am. J. Physiol., 278: 572-577.
Direct Link - Rana, S.V. and S. Verma, 1996. Protective effects of GSH, Vitamin E and selenium on lipid peroxidation in cadmium fed rats. Biol. Trace Elem. Res., 51: 161-168.
Direct Link - Bagchi, D., M. Bagchi, E.A. Hassoun and S.J. Stohs, 1996. Cadmium-induced excretion of urinary lipid metabolites, DNA damage, glutathione depletion and hepatic lipid peroxidation in Sprague-Dawley rats. Biol. Trace Elem. Res., 52: 143-154.
CrossRefDirect Link - Sunitha, S., M. Nagaraj and P. Varalakshmi, 2001. Hepatoprotective of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium induced heptotoxicity in rats. Fitoterapia, 72: 516-523.
PubMed - Shukla, G.S., J.F. Chiu and B.A. Hart, 2000. Cadmium induced in the gene expression of the regulatory subunit of gamma glutamylcysteine synthetase in rat lung and alveolar epithelial cells. Toxicology, 151: 45-54.
Direct Link - Karmakar, R., S. Banik, S. Bandyopadhay and M. Chatterjee, 1998. Cadmium induced alterations of hepatic lipid peroxidation, glutathione S-transferase activity and reduced glutathione level and their possible correlation with chromosomal aberration in mice: A time course study. Mutat. Res., 397: 183-190.
Direct Link - Brozoska, M.M., J. Moniuszko-Jakoniuk, M. Jurczuk, M. Galazyn-Sidorczuk and J. Rogalska, 2000. Effect of short-term ethanol administration of cadmium retention and bioelement metabolism in rats continuously exposed to cadmium. Alcohol Alcoholism, 35: 439-445.
Direct Link - Liu, Y., J. Liu, S.S. Habeebu and C.D. Klaassen, 1999. Metallothionein protects against the nephrotoxicity produced by chronic Cd MT exposure. Toxicol. Sci., 50: 221-227.
Direct Link - Sidhu, P., M.L. Garg and D.K. Dhawan, 2004. Protective role of zinc in nickel induced hepatotoxicity in rats. Chemico-Biol. Interact., 150: 199-209.
CrossRef - Koizumi, T., H. Shirakura, H. Kumagi, H. Tatsumoto and K.T. Suzuki, 1996. Mechanism of cadmium induced cytotoxicity in rat hepatocytes: cadmium induced active oxygen related permeability changes of the plasma membrane. Toxicology, 114: 125-134.
Direct Link - Joshi, S., S.K. Hasan, R. Chandra, M.M. Husain and R.C. Srivastava, 2004. Scavenging action of zinc and green tea polyphenol on cisplatin and nickel induced nitric oxide generation and lipid peroxidation in rats. Biomed. Environ. Sci., 17: 402-409.
Direct Link - Bettger, W.T., 1993. Zinc and selenium site specific versus general antioxidant. Can. J. Physiol. Pharmacol., 71: 721-724.
Direct Link - Powell, S.R., 2000. The antioxidant properties of zinc. J. Nutr., 130: 1447S-1454S.
CrossRefDirect Link - Sato, M. and I. Bremner, 1993. Oxygen free radicals and metallothionein. Free Radic. Biol. Med., 14: 325-337.
PubMed - Jacobes, R.M., A.O. Jones, M.R. Fox and J. Lener, 1983. Effects of dietary zinc, manganese and copper on tissue accumulation of cadmium by Japanese quail. Proc. Soc. Exp. Biol. Med., 172: 34-38.
Direct Link