Changes of liver xenobiotic-metabolizing function at different status of hepatic injury / 中国药理学通报

ABSTRACT

Aim The changes and characteristics of liver drug-metabolizing and antioxiditive functions in different status of hepatic injury was investigated to provide support for clinical drug treatments in hepatic fibrosis. Methods Carbon tetrachloride (CCl 4) and other mixture factors were used to make animal model of acute hepatic injury, hepatic fibrosis and cirrhosis, respectively. Subcelluar fractions of liver were prepared by differential centrifugation. Activities of drug-metabolizing and antioxidative enzymes were monitored. Results Levels of phase I enzymes-cytochrome P450 (CYP), CYP1A1 (7-ethoxyresorufin O-deethylation), CYP2E1 (aniline hydroxylation), CYP3A1/2 (erythromycin N-demethylation), and phase Ⅱ enzymes-glutathione S-transferase (GST) were reduced remarkably in hepatic microsomes in different hepatic injury status in a time-dependent manner. However, the activity of CYP2E1 came to be the lowest in acute hepatic injury and recovered gradually when injury time was prolonged. In hepatic fibrosis, the activities of CYP1A,CYP2E1,CYP3A and GST reached 68%,56%,81% and 59%, respectively, of the control, and the functions of antioxidative enzymes in cytosol GST,catalase(Cat) and glutathione peroxidase(GSH-Px) declined to 85%,76% and 54%, respectively, of the control. Conclusion The xenobiotic-metabolizing abilities in liver with hepatic fibrosis were distinctly decreased, which constantly relates with the degrees and the lengths of hepatic injury.