MECHANISM OF CARBON-TETRACHLORIDE AUTOPROTECTION - AN IN-VIVO STUDY BASED ON C-13-AMINOPYRINE AND C-13-GALACTOSE BREATH TESTS

This study was conducted to evaluate in vivo the hepatotoxic effects of CCl4 administration to rats using C-13 breath tests: aminopyrine breath test (ABT) was used to monitor CCl4-induced cytochrome P450 inactivation, and galactose breath test (GBT) to quantitatively measure the CCl4-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 CCl4. The protection induced by a first CCl4 dose against a second one paralleled cytochrome P450 inactivation: second CCl4 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 CCl4 dosing schedule in the rat CCl4-induced cirrhosis model.