title: Manganese induces oxidative stress, redox state unbalance and disrupts membrane bound ATPases on murine neuroblastoma cells in vitro: protective role of silymarin.
abstract: Manganese (Mn) is an essential trace element required for ubiquitous enzymatic reactions. Chronic overexposure to this metal may promote potent neurotoxic effects. The mechanism of Mn toxicity is not well established, but several studies indicate that oxidative stress play major roles in the Mn-induced neurodegenerative processes. Silymarin (SIL) has antioxidant properties and stabilizes intracellular antioxidant defense systems. The aim of this study was to evaluate the toxic effects of MnCl(2) on the mouse neuroblastoma cell lines (Neuro-2A), to characterize the toxic mechanism associated with Mn exposure and to investigate whether SIL could efficiently protect against neurotoxicity induced by Mn. A significant increase in LDH release activity was observed in Neuro-2A cells associated with a significant decrease in cellular viability upon 24 h exposure to MnCl(2) at concentrations of 200 and 800 μM (P < 0.05) when compared with control unexposed cells. In addition, exposure cells to MnCl(2) (200 and 800 μM), increases oxidant biomarkers and alters enzymatic and non enzymatic antioxidant systems. SIL treatment significantly reduced the levels of LDH, nitric oxide, reactive oxygen species and the oxidants/antioxidants balance in Neuro-2A cells as compared to Mn-exposed cells. These results suggested that silymarin is a powerful antioxidant through a mechanism related to its antioxidant activity, able to interfere with radical-mediated cell death. SIL may be useful in diseases known to be aggravated by reactive oxygen species and in the development of novel treatments for neurodegenerative disorders such as Alzheimer or Parkinson diseases.
authors.affiliation: Animal Physiology Laboratory, Life Sciences Department, Faculty of Sciences, UR/08-73, Sfax University, BP 1171, 3000, Sfax, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.forename: Khaled
authors.initials: K
authors.lastname: Trabelsi
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
authors.forename: Ghada
authors.initials: G
authors.lastname: Mkannez
authors.forename: Héla
authors.initials: H
authors.lastname: Kallel
authors.forename: Najiba
authors.initials: N
authors.lastname: Zeghal
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015227:Lipid Peroxidation; D008345:Manganese / Q000633:toxicity*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012838:Silymarin; D008345:Manganese; D000251:Adenosine Triphosphatases