Neurochemical Research

, Volume 37, Issue 3, pp 469–479 | Cite as

Improvement of Cerebellum Redox States and Cholinergic Functions Contribute to the Beneficial Effects of Silymarin Against Manganese-Induced Neurotoxicity

  • Yassine Chtourou
  • Hamadi Fetoui
  • El Mouldi Garoui
  • Tahia Boudawara
  • Najiba Zeghal
Original Paper


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.


Manganese Cerebellum Silymarin Inducible nitric oxide synthase Acetylcholinesterase 



The authors are indebted to Miss Dalenda Kchaou for her assistance in histolological techniques. The present work was supported by the grants of DGRST (Appui à la Recherche Universitaire de base, ARUB 99/UR/08-73) Tunisia.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yassine Chtourou
    • 1
  • Hamadi Fetoui
    • 1
  • El Mouldi Garoui
    • 1
  • Tahia Boudawara
    • 2
  • Najiba Zeghal
    • 1
  1. 1.Animal Physiology Laboratory, Life Sciences Department, UR/08-73, Sfax Faculty of SciencesUniversity of SfaxSfaxTunisia
  2. 2.Anatomopathology Laboratory, CHU Habib BourguibaUniversity of SfaxSfaxTunisia

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