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 the substantia nigra is thought to involve excessive production of free radicals, dopamine autoxidation, defects in the expression of glutathione peroxidase, attenuated levels of reduced glutathione, altered calcium homeostasis, 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 radical production, compromised mitochondrial activity and excessive lipid peroxidation. In the present study, several dietary antioxidant compounds, monoamine oxidase inhibitors and ergogenic compounds were examined for protective action against neurotoxicity induced by L-glutamate (15 mM) or MPP+-HCl (5 mM) in a plastic adhering variant of murine pheochromocytoma cells. The results show no significant protective effects exhibited by azulene, (+)-catechin, curcrumin, (-)-epigallocatechin gallate, green tea, morin, pygnogenol, silymarin, clove oil, garlic oil or rosemary, extract. Compounds, which were effective in providing protection against L-glutamate-induced cell death, were coenzyme Q-0, coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. Compounds, which provided protection against MPP+-HCl toxicity, were allopurinol, coenzyme Q-10, L-deprenyl, N-acetyl-L-cysteine and sesame oil. In both models, significant protection was achieved in the presence of coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. These results indicate that the mechanism of cell death in both of these toxicity models is most likely not related to the destructive effects of free radicals.
Mazzio
E
E
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee 32307, USA.
Huber
J
J
Darling
S
S
Harris
N
N
Soliman
K F
KF
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D018846:Excitatory Amino Acids / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D007700:Kinetics; D016202:N-Methylaspartate / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015655:1-Methyl-4-phenylpyridinium