Improvement of Cerebellum Redox States and Cholinergic Functions Contribute to the Beneficial Effects of Silymarin Against Manganese-Induced Neurotoxicity |
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Authors: | Yassine Chtourou Hamadi Fetoui El Mouldi Garoui Tahia Boudawara Najiba Zeghal |
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Institution: | (1) Animal Physiology Laboratory, Life Sciences Department, UR/08-73, Sfax Faculty of Sciences, University of Sfax, BP1171, 3000 Sfax, Tunisia;(2) Anatomopathology Laboratory, CHU Habib Bourguiba, University of Sfax, Sfax, Tunisia; |
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Abstract: | Manganese (Mn) is a potent neurotoxin involved in the initiation and progression of various cognitive disorders. Oxidative
stress is reported as one of accepted mechanisms of Mn toxicity. The present study was designed to explore the effects of
silymarin, a natural antioxidant, in attenuating the toxicity induced by Mn in rat cerebellum. In this investigation, rats
were treated orally with MnCl2 (20 mg/ml) for 30 days, subsets of these animals were treated intraperitoneally daily with silymarin (100 mg/kg) along with
respective controls. Mn exposure caused a marked oxidative stress in cerebellum as indicated by a significant decrease in
the activities of enzymatic antioxidants like superoxide dismutase, catalase and glutathione peroxidase and in the levels
of non-enzymatic antioxidants like reduced glutathione (GSH), total thiols and vitamin C. Conversely an increase was obtained
in lipid and protein markers such as thiobarbituric reactive acid substances, lipid hydroperoxide and protein carbonyl products
contents. A Significant increase in acetylcholinesterase and a decrease in Na+/K+-ATPase activities were also shown, with a substantial rise in the expression of acetylcholinesterase and inducible nitric
oxide synthase (iNOS), and nitric oxide levels. The potential effect of SIL to prevent Mn induced neurotoxicity was also reflected
by histopathological observations. Rats exposed to Mn showed a reduced number and morphological alterations of cerebellar
Purkinje cells. These phenomenons were completely reversed by SIL co-treatment. We concluded that silymarin may protect against
Mn-induced oxidative stress in cerebellum by inhibiting both lipid and protein oxidation and by activating acetylcholinesterase
and inducible nitric oxide synthase (iNOS) gene expression. |
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