Acetylsalicylic acid and acetaminophen protect against MPP+-induced mitochondrial damage and superoxide anion generation.
The effects of 1-methyl-4-phenylpyridinium (MPP+) has been extensively researched due to its selective toxicity to dopaminergic neurons. Mitochondrial dysfunction which is common in the etiology of Parkinson's disease (PD), has been widely implicated in MPP+-induced toxicity. MPP+-induced mitochondrial dysfunction is believed to result in the generation of free radicals. This study was therefore performed to assess the effect of MPP+ on mitochondrial function and the ability of MPP+ to generate superoxide free radicals. Furthermore, we assessed the ability of the non-narcotic analgesics, acetaminophen and acetylsalicylic acid to prevent any diliterious effects of the potent neurotoxin, MPP+, on mitochondrial function and superoxide anion generation, in vivo. Acetylsalicylic acid and acetaminophen prevented the MPP+-induced inhibition of the electron transport chain and complex I activity. In addition, acetylsalicylic acid and acetaminophen significantly attenuated the MPP+-induced superoxide anion generation. Furthermore the results provide novel data explaining the ability of these agents to prevent MPP+-induced mitochondrial dysfunction and subsequent reactive oxygen species generation. While these findings suggest the usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, acetylsalicylic acid appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.
Maharaj
H
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Division of Pharmacology, Faculty of Pharmacy, P.O. Box 94, Rhodes University, Grahamstown, 6139, South Africa.
Maharaj
D S
DS
Daya
S
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D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009580:Nitroblue Tetrazolium; D016877:Oxidants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016877:Oxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D000082:Acetaminophen; D009247:NADH, NADPH Oxidoreductases; D001241:Aspirin; D015655:1-Methyl-4-phenylpyridinium