Drug metabolizing activity in rats with chronic liver injury induced by carbon tetrachloride: relationship with the content of hydroxyproline in the liver.
The drug metabolizing activity of rat liver during long-term administration of carbon tetrachloride (CCl4), and its relationship with the content of hydroxyproline (Hyp) in the liver were examined. The contents of cytochrome P-450 (P-450) and cytochrome b5 (b5) and the metabolization of aniline, aminopyrine, 7-ethoxycoumarin (7-EC) and benzo(a)pyrene (B(a)P) in the microsomal fraction were examined five days after the final administration of CCl4. The contents of P-450 and b5 and the activity to metabolize the four substrates were gradually reduced as the Hyp content in the liver increased. However, aminopyrine N-demethylation and B(a)P hydroxylation, particularly the latter, was more reduced than aniline hydroxylation and 7-EC O-deethylation in the early stage of hepatic fibrosis. Such differences may be due mainly to the different P-450 subtypes affected by CCl4.
D000818:Animals; D001711:Biotransformation; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003573:Cytochrome b Group / Q000032:analysis; D015786:Cytochromes b5; D006909:Hydroxyproline / Q000032:analysis*; D008099:Liver / Q000032:analysis / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006909:Hydroxyproline