Acetaminophen and aspirin inhibit superoxide anion generation and lipid peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats.
We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs inhibited cyanide-induced superoxide anion generation, as well as lipid peroxidation in rat brain homogenates, the combination of the agents resulting in a potentiation of this effect. Acetaminophen or aspirin when administered alone or in combination, did not alter dopamine (DA) levels in the forebrain or in the striatum. Intranigral infusion of MPP+ in rats caused severe depletion of striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic post-treatment of acetaminophen afforded partial protection, whereas similar treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA depletion. While these findings suggest usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.
Maharaj
D S
DS
Department of Pharmacy, Division of Pharmacology, Rhodes University, PO Box 94, Grahamstown 6140, South Africa.
Saravanan
K S
KS
Maharaj
H
H
Mohanakumar
K P
KP
Daya
S
S
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D009580:Nitroblue Tetrazolium; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D015259:Dopamine Agents; D009498:Neurotoxins; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D000082:Acetaminophen; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001241:Aspirin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine