Mechanism of carbon tetrachloride autoprotection: An in vivo study based on 13C-aminopyrine and 13C-galactose breath tests

Abstract

This study was conducted to evaluate in vivo the hepatotoxic effects of CCL 4 administration to rats using 13C breath tests: aminopyrine breath test (ABT) was used to monitor CCL 4-induced cytochrome P450 inactivation, and galactose breath test (GBT) to quantitatively measure the CCl 4-induced decrease of liver function. The ABT results showed profound aminopyrine demethylation inhibition lasting for three days and complete recovery at day 7, while GBT results were decreased only one day after CCl 4. The protection induced by a first CCl 4 dose against a second one paralleled cytochrome P450 inactivation: a second CCl 4 dose given three days after the first one induced no GBT decrease and a mild increase of serum transaminase activities. On the other hand, the second dose administered 7 days after the first one produced a GBT decrease similar to the one observed after the first one. These results should be taken into consideration to determine the optimal CCl 4 dosing schedule in the rat CCl 4-induced cirrhosis model.