Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells

The neuropathology associated with Parkinson's disease within and around th e substantia nigra is thought to involve excessive production of free radic als, dopamine autoxidation, defects in the expression of glutathione peroxi dase, alternated levels of reduced glutathione, alter-ed calcium homeostasi s, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and N -methyl-4-phenylpyridinium ion (MPP+), both are thought to involve free rad ical production, compromised mitochondrial activity and excessive lipid per oxidation. In the present study, several dietary antioxidant compounds, mon oamine oxidase inhibitors and ergogenic compounds were examined for protect ive action against neurotoxicity induced by L-glutamate (15 mM) ol MPP+-HCl (5 mM) iii a plastic adhering variant of murine pheochromocytoma cells. Th e results show no significant protective effects exhibited by azulene, (+)- catechin, curcumin, epigallocatechin gallate, green tea, morin, pygnogenol, silymarin, clove oil, garlic oil or rosemary extract. Compounds, which wer e effective in providing protection against L-glutamate-induced cell death, were coenzyme (O) under tilde -0, coenzyme (O) under tilde, L-deprenyl and N-acetyl-L-cysteine. Compounds, which provided protection against MPP+-HCl toxicity, were allopurinol, coenzyme (O) under tilde -10, L-deprenyl, N-ac etyl-L-cystene and sesame oil. In both models, significant protection was a chieved ill the presence of coenzyme (O) under tilde -10, L-deprenyl and N- acetyl-L-cysteine. These results indicate that the mechanism of cell death in both of these toxicity models is moss likely not related to the destruct ive effects of free radicals. (C) 2001 Elsevier Science Inc. All rights res erved.