TY - JOUR T1 - RELATIONSHIP OF ALCOHOL METABOLISM TO THE POTENTIATION OF CCl<sub>4</sub> HEPATOTOXICITY INDUCED BY ALIPHATIC ALCOHOLS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 481 LP - 488 VL - 183 IS - 3 AU - GEORGE J. TRAIGER AU - GABRIEL L. PLAA Y1 - 1972/12/01 UR - http://jpet.aspetjournals.org/content/183/3/481.abstract N2 - The effect of pyrazole on 1) the in vivo metabolism of ethanol and isopropanol and 2) the ethanol and isopropanol-induced potentiation of CCl4 hepatotoxicity was studied in rats. Pyrazole delayed the elimination of ethanol. Pyrazole plus ethanol, 18 hours prior to a challenging dose of CCl4, yielded serum glutamic pyruvic transaminase activities that were 6-fold greater than those observed with ethanol plus CCl4, with hepatic glucose-6-phosphatase activity also reflecting enhanced toxicity. Acetaldehyde did not display the ability to potentiate CCl4 hepatotoxicity. Pyrazole markedly enhanced the slight augmentation of CCl4 hepatotoxicity produced by 1-butanol 18 hours prior to CCl4. Blood isopropanol concentrations declined more slowly than those of ethanol. With the decline of isopropanol, there was a rise in blood acetone concentrations, the maximum occurring 7 to 10 hours after administration of isopropanol. Pyrazole, 15 minutes prior to isopropanol, produced a delay in the rate of isopropanol elimination, with a concomitant decrease in the rate of acetone formation. Pyrazole, 15 minutes prior to isopropanol, diminished the enhanced response of CCl4 to isopropanol, with serum glutamic pyruvic transaminase levels reduced to 40% of that found for isopropanol and CCL4; triglyceride levels also reflected reduced hepatotoxicity. An 18-hour pretreatment with acetone enhanced CCl4 toxicity (elevated serum glutamic pyruvic transaminase activity). These results indicate that the potentiation observed after ethanol is associated with nonmetabolized ethanol, while acetone derived during the in vivo oxidation of isopropanol appears to contribute to the response observed after isopropanol. © 1972 by The Williams &amp; Wilkins Co. ER -