Neuroprotective effects of alpha-tocopherol on oxidative stress in rat striatal cultures

Oxidative stress caused by an increase in free radicals plays an important role in neuronal death. We investigated the effects of alpha-tocopherol on oxidative stress-induced cytotoxicity using primary cultures of rat striatal neurons. alpha-Tocopherol at concentrations of 1-10 microM significantly prevented cytotoxicity induced by superoxide radical (O(2(-)) donor, 1,1'-dimethyl-4,4'-bipyridium dichloride (paraquat). In contrast, alpha-tocopherol did not affect the cytotoxicity of hydrogen peroxide (H(2)O(2)), which enhances hydroxyl radical (.OH) formation by metal-catalyzed Fenton reactions. alpha-Tocopherol significantly inhibited the cytotoxicity of nitric oxide (NO) donors, S-nitrosocysteine and 3-morpholinosydnonimine (SIN-1). alpha-Tocopherol showed potent protection against cytotoxicity induced by L-buthionine-[S,R]-sulfoximine (BSO), which causes depletion of intracellular glutathione. Moreover, alpha-tocopherol afforded a moderate but significant inhibition of cytotoxicity induced by a non-specific protein kinase inhibitor, staurosporine, which is known to induce apoptosis in many types of cells including neurons. These results suggest that alpha-tocopherol protects striatal neurons by the reduction of oxidative stress, presumably by decreasing intracellular O(2)(-) levels, and at least partly by the inhibition of apoptosis.