Mechanism of carbon tetrachloride autoprotection: an in vivo study based on 13C-aminopyrine and 13C-galactose breath tests.
This study was conducted to evaluate in vivo the hepatotoxic effects of CCl4 administration to rats using 13C 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: a 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.
Mion
F
F
URA 1341, CNRS, Université Claude Bernard, Lyon, France.
Géloën
A
A
Rousseau
M
M
Brazier
J L
JL
Minaire
Y
Y
D000410:Alanine Transaminase / Q000097:blood; D000632:Aminopyrine / Q000032:analysis*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002247:Carbon Isotopes; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000503:physiopathology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D005690:Galactose / Q000032:analysis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013997:Time Factors
D002247:Carbon Isotopes; D065607:Cytochrome P-450 Enzyme Inhibitors; D000632:Aminopyrine; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005690:Galactose; D010634:Phenobarbital