Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats.

ABSTRACT

BACKGROUND: Cadmium is a potent neurotoxic heavy metal, which induces oxidative stress and membrane disturbances in brain. Melatonin is an effective antioxidant and free radical scavenger against oxidative stress. The present study was designed to investigate the neuroprotective efficacy of melatonin in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), levels of lipid peroxidation, protein carbonyls, non-enzymatic antioxidant, enzymatic antioxidant status, membrane bound ATPases and histopathology in the brain of rats. MATERIALS AND METHODS: Twenty four male albino rats were used. Cadmium induced oxidative neurotoxicity was induced by oral administration of Cd for four weeks. Melatonin was pretreated along with Cd for four weeks to assess its neuroprotective activity against Cd intoxication. Rats treated with vehicles alone were used as controls. RESULTS: Rats intoxicated with cadmium (5 mg/kg/day) for 4 weeks significantly (p < 0.05) reduced the AChE levels in the plasma and brain, elevated the levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides and protein carbonyls along with the significant (p < 0.05) decrease in the levels of non-enzymatic antioxidants (GSH, TSH and vitamins C and E), enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and membrane bound ATPases in the brain tissue. Administration of melatonin (10 mg/kg/day) for 4 weeks in cadmium intoxicated rats significantly (p < 0.05) diminished the levels of oxidative stress markers, lipid peroxidation and protein carbonyls in brain and significantly (p < 0.05) elevated the levels of nonenzymatic and enzymatic antioxidants, brain and the activities of AChE, enzymatic antioxidants and ATPases in brain. The histopathological studies in the brain of rats also supported that melatonin markedly reduced the Cd induced pathological changes and preserved the normal histological architecture of the brain tissue. CONCLUSIONS: The results of the present study suggest that melatonin may be beneficial in combating the cadmium induced oxidative neurotoxicity in the brain of rats.