Effect of fasting, diethyl maleate, and alcohols on carbon tetrachloride-induced hepatotoxicity

Abstract

The effect of fasting, diethyl maleate treatment, and methanol, ethanol, iso-propanol, or tert-butanol treatment on carbon tetrachloride (CCl 4)-induced hepatotoxicity in male Sprague-Dawley rats was studied. A 24-hr fast and the administration of diethyl maleate were found to be equipotent and not additive in potentiating CCl 4-induced hepatotoxicity; this potentiation appeared to be due to a depletion of hepatic glutathione (GSH) levels. Concomitant diurnal variations in hepatic GSH content and in CCl 4-induced hepatotoxicity also suggested hepatic GSH involvement in CCl 4-induced hepatic damage. Whereas ethanol has been reported to potentiate CCl 4-induced hepatotoxicity and to lower hepatic GSH levels, the present study suggested that these effects are due to an ethanol-induced loss of body weight. Methanol, iso-propanol, and tert-butanol, on the other hand, show the same maximal potentiation of CCl 4-induced hepatotoxicity and do so without inducing a depletion of hepatic GSH content or producing a loss of body weight. In contrast to a previous report, however, methanol was found to be markedly less effective on an equimolar basis than either iso-propanol or tert-butanol in potentiating CCl 4-induced hepatotoxicity. The study suggests that GSH is an important modulator of CCl 4-induced hepatotoxicity and also suggests that methanol, iso-propanol, and tert-butanol, but not ethanol, potentiate CCl 4-induced hepatotoxicity by a mechanism that does not involve altered hepatic GSH levels.