Protective effect of manganese in cadmium-induced hepatic oxidative damage, changes in cadmium distribution and trace elements level in mice
Oxidative tissue damage is considered an early sign of cadmium (Cd) toxicity and has been linked with carcinogenesis. Manganese(II) - at low doses, was found to act as a potent antioxidant against oxidative stress in different in vitro systems producing lipid peroxidation conditions. The present study investigates in vivo antioxidant effects of Mn2+ pretreatment in acute Cd intoxication with regard to lipid peroxidation, antioxidant defense system and cadmium distribution in the tissues of mice. Four groups of male mice (n=7-8) were used: Cd group was injected sc a single dose of CdCl2 · 2 1/2 H2O (7 mg/kg b.w.); Cd+Mn group was treated ip with MnCl2 · 4H2O (20 mg/kg b.w.) 24 hours before Cd intoxication; Mn group received manganese treatment only; Control group received saline only. Twenty-four hours after Cd intoxication an increased lipid peroxidation (p<0.05), depleted GSH level (p<0.01), increased activity of GSH-Px (p<0.05) and inhibited CAT activity (p<0.01) were found in Cd-treated group compared to controls. Manganese(II) pre-treatment either completely prevented (LP, GSH, GSH-Px) or significantly attenuated (CAT) these changes. Manganese(II) treatment alone decreased LP, enhanced hepatic GSH level and had no effect on antioxidant enzymes compared to control group. A significant increase of Cd concentration in the liver and decreased Cd concentration in the kidneys and testes were found in Cd+Mn treated mice compared to Cd-only treated group. The effect of manganese may result from a different metallothionein induction in particular organs. Manganese(II) pretreatment attenuated the interference of cadmium with Ca homeostasis, the alteration in Zn and Cu levels remained mostly unaffected.
Aebi H. (1972). Catalase, in: Methods of Enzymatic Analysis, vol.2, Bergmeyer HU (ed.). Academic Press: New York; 673-684.
Casalino E, Calzaretti G, Sblano C, Landriscina C. (2002a). Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by cadmium. Toxicology179: 37-50.
Casalino E, Valzaretti G, Sblano C, Landriscina V, Felice Tecce M and Landriscina C. (2002b). Antioxidant effect of hydroxytyrosol (DPE) and Mn2+ in liver of cadmium-intoxicated rats. Comp Biochem Physiol Part C133: 625-632.
Cavallini L, Valente M, Bindoli A. (1983). Inhibition of lipid peroxidation by manganese. Inorg Chim Acta, 79: 224-225.
Chen MT, Sheu JY, Lin TH. (2004). Protective effects of manganese against lipid peroxidation. J Toxicol Environ Health A.61: 569-577.
Coassin M, Ursini F and Bindoli A. (1992). Antioxidant effect of manganese. Arch. Biochem Biophys299: 330-333.
Dobson AW, Erikson KM and Aschner M. (2004). Manganese neurotoxicity. Ann N Y Acad Sci1012: 115-128.
Goering PL and Klaassen CD. (1985). Mechanism of manganese-induced tolerance to cadmium lethality and hepatotoxicity. Biochem Pharmacol34: 1371-1379.
Günzler VA, Kremers H and Flohe L. (1974). An improved coupled test procedure for glutathione peroxidase (EC 22.214.171.124.) in blood. Z Klin Chem Biochem12: 444-448.
HaMai D and Bondy SC. (2004). Oxidative basis of manganese neurotoxicity. Ann N Y Acad Sci1012: 129-141.
Himeno S, Yanagiya T, Enomoto S, Kondo Y, Imura N. (2002). Cellular cadmium uptake mediated by the transport system for manganese. Tohoku J Exp Med196: 43-50.
Himeno S, Yanagiya T, Fujishiro H. (2009). The role of zinc transporters in cadmium and manganese transport in mammalian cells. Biochimie91: 1218-1222.
Hussain S and Ali SF. (1999). Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats. Neuroscience Letters261: 21-24.
International Agency for Research on Cancer Monographs. (1993). Cadmium, vol. 58. Lyon: IARC Press, 119-238.
Kotyzová D, Caisová D, Eybl V. (1990). The influence of manganese pre-treatment on cadmium toxicity. Cs. fysiologie 39: 144 (abstract, in Czech)
Mihara M, Uchiyama M. (1978). Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Analyt Biochem86, 271-278.
Pillai A, Gupta S. (2005). Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: effects of vitamin E and Mn2+. Free Radic Res39: 707-712.
Santamaria AB, Sulsky SI. (2010). Risk assessment of an essential element: manganese. J Toxicol Environ Health A73: 128-155.
Sedlak J, Lindsay, RH. (1968). Estimation of total, proteinbound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analyt Biochem25, 192-205.
Sziráki I, Rauhala P, Chiueh CC. (1995). Novel protective effect of manganese against ferrous citrate-induced lipid peroxidation and nigrostriatal neurodegeneration in vivo. Brain Res698: 285-287.
Sziráki I, Rauhala P, Koh KK, van Bergen P and Chiueh CC. (1999). Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoprotein conjugation. Neurotoxicology20: 455-466.
Valachová K, Kogan G, Gemeiner P, Šoltés L. (2010). Protective effects of manganese(II) chloride on hyaluronan degradation by oxidative system ascorbate plus cupric chloride. Interdisc Toxicol3, 26-34.
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact160: 1-40.