Effect of tramadol on level of CYP450 and liver function in rats

Objective To investigate the changes of hepatic CYP450 activity and liver function in tramadol dependent rats. Methods Total 30 SD rats were divided into blank group, positive control group and experimental group, with 10 rats in each group. Each group was administered with saline, 80 mg/(kg·d) phenobarbital and 60 mg/(kg·d) tramadol. The rat model of tramadol dependent rats was established. Cocktail in vitro incubation method combined with liquid mass spectrometry (LC-MS) technology were used to test the isozymes activities of CYP1A2, CYP2B1, CYP2C11, CYP2D2, CYP2E1, CYP3A1 in rat liver were measured, and RT-qPCR technique was used to detect the level of mRNA expression of the above isozymes, and the blood biochemical analyzer was used to analyze the liver function index. Results ① Compared with the blank group, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 in the positive control group were (190.15±33.577), (98.018±36.00), (1 348.79±40.76), (3 214.66±133.51) and (292.76±33.32) μg/ml, which were significantly higher than those in the blank group (P<0.05). The difference was statistically significant. ②Compared with the blank group, the expression of CYP1A2, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 mRNA in the positive control group was significantly up, (89.88±14.22)%, (95.12±16)%, (351.25±32.33)%, (556.85±42.88)% and (52.56±11.12)%, and the difference was statistically significant, and there was no significant change in CYP2D2 mRNA. The expression of CYP1A2, CYP2B1, CYP2E1 and CYP2D2 mRNA in the experimental group was up (75.12±21.45)%, (66.32±18.14)%, (81.35±23.55)% and (382.74±33.25)%. The difference was statistically significant. There was no significant change in the expression of CYP2C11 and CYP3A1 mRNA. ③In the liver biochemical index level, compared with the blank group, the content of ALT, AST and LDH in the positive control group and the experimental group increased significantly, and the results were statistically significant. Conclusion The abuse of tramadol may induce an increased activity of CYP1A2, CYP2B1, CYP2E1 and CYP2D2 and liver injury in rats.