Dynamic monitoring of blood biochemistry and CYP450 metabolic changes in cirrhotic rats

Liver cirrhosis, a progressive disease, presents no obvious symptoms in the early stage. So far, no comprehensive study has focused on the dynamic changes of liver function and the metabolic ability of CYP450 enzymes. In this study, thirty-two Sprague-Dawley Rats were randomly divided into two groups: Control-group (n=10) and cirrhosis-group (n=22). The cirrhotic rat model was developed by subcutaneous injection of CCl4 for 8 weeks. The blood biochemistry was monitored at 0, 2, 4, 6, 8, and 10 weeks. The metabolic ability of CYP450 was evaluated by pharmacokinetics of six CYP450 probe drugs at 10 weeks. The results showed that the level of alkaline phosphatase (AKP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bile acid (BA) were all increased significantly at 2 weeks, and were subsequently maintained at a high level. Albumin gradually decreased and globulin (GLO) gradually increased, showing a statistically significant difference at 4 weeks (P<0.05). The pharmacokinetic study showed that except for testosterone, the AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞), t1/2, and Tmax of the five probe drugs phenacetin, bupropoin, omeprazole, tolbutamide, and metoprolol were all increased in cirrhotic rats compared with the control group (P<0.05). In conclusion, ALT, AST, AKP, BA, and GLO can be used as sensitive indices for the early stage development of cirrhosis, and the metabolic ability of CYP450 enzymes was significantly inhibited.