High molecular weight protein aggregates formed in the liver of the rat following large doses of paracetamol.
Paracetamol (200 and 500 mg kg-1) was given intraperitoneally to rats pretreated with 3-methylcholanthrene for 3 days. Glutamic oxalacetic acid transaminase (GOT) activity in plasma increased in rats receiving 500 mg kg-1 paracetamol. Plasma GOT activity was low at the dose of 200 mg kg-1, but the same dose to diethyl maleate pretreated rats increased the GOT activity. High mol. wt protein aggregates were found to be formed in liver homogenates and microsomes of rats which showed high plasma GOT activity, accompanied by depletion of hepatic glutathione. The formation of protein aggregates in the liver of rats following large doses of paracetamol suggests a contribution of lipid peroxidation to paracetamol-induced hepatotoxicity.
Minamide
Y
Y
Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.
Horie
T
T
Awazu
S
S
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000097:blood; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D011506:Proteins; D000082:Acetaminophen; D008748:Methylcholanthrene; D001219:Aspartate Aminotransferases; D005978:Glutathione