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Research Article

Modification of Methanol Potentiation of CC14 Toxicity in Rats by Chloramphenicol and Salicylate

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Pages 143-154
Published online: 27 Sep 2008

ABSTRACT

The mechanism by which methanol potentiates CC14 hepatotoxicity was studied in rats. Chloramphenicol, an inhibitor of cytochrome P-450, blocked the increase of serum glutamate-oxaloacetate trans-minase activity enhanced by methanol pretreatment of rats exposed to CC14. Chloramphenicol also decreased microsomal lipid peroxidation in both CC14 and methanol-pretreated, CC14 -intoxicated animals when measured 30 minutes after exposure. Chloramphenicol prevented the loss of glucose 6-phosphatase activity after CC1 and methanol. Sodium salicylate, which lowers the level of NADPH in the hepatocyte, blocked mthanol potentiation of CC14 damage as measured by the elevation of serum GOT activity. Therejore, methanol may potentiate CC14 hepatotoxicity by stimulation of CC14 bioactivation by cytochrome P-450 via an increase in the level of reduced NAD(P)H in the liver.

 

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