Manganese neurotoxicity and protective effects of resveratrol and quercetin in preclinical research.

Abstract

Exposure to Mn results in a neurological syndrome known as manganism. We examined how 4-week Mn exposure (20mg/kg MnCl2po, 5days/week) induces neurotoxic effects in rats. Oxidized-to-reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity, vitamin E content and caspase-3 activity were measured in several rat brain structures. Further, we examined protective effects of the polyphenols: resveratrol (R) or quercetin (QCT) against Mn-induced neurotoxicity. After exposure to Mn, we found a rise in GSSG/GSH ratio and a reduction in SOD activity in the rat striatum (STR), while in the nucleus accumbens (NAC) decreases in alpha-tocopherol content and in SOD activity were noted. In the frontal cortex (FCX), an enhancement in GSSG/GSH ratio and a reduction in SOD and CAT activities were observed. In the cerebellum (CER), a significant increase in the caspase-3 activity paralleled a rise in the GSSG/GSH ratio and a diminution of SOD activity. In the rat hippocampus (HIP), Mn evoked an enhancement in GSSG/GSH ratio. There were no changes in the MDA levels. Pretreatment with R and QCT protected against the Mn-induced (i) enhancement in GSSG/GSH ratio in the STR, (ii) decreases in the NAC alpha-tocopherol content and (iii) reduction in SOD activity in FCX, NAC and CER. Repeated Mn administration induces toxic effects in several rat brain structures and treatment with R and QCT may be a potential therapeutic strategy to attenuate the metal neurotoxicity.