Effect of nizatidine on rat CYP1A2 expression and activity

Aim The present study investigates the influence of nizatidine on rat liver CYP1A2 activity in vivo and in vitro,respectively.Methods We employed HPLC to measure the metabolites of caffeine in the blood and calculated the ratio between the metabolites and caffeine,which was used to evaluate the effect of nizatidine on rat CYP1A2 activity in vivo;We also detected the CYP1A2 activity in microsomal reconstituted system by analysis of paracetamol with HPLC.Finally,we examined the expression of CYP1A2 from microsomes treated with nizatidine or control groups using Western blot.Results The metabolism of caffeine in treated groups was 29.6%±12.5%、32.4%±13.4%、37.5%±15.0%,with different concentration of nizatidine(14,27,54 mg·kg~(-1))compared with 26.9%±11.9% in the control group,which was no significant difference among the groups(P0.05).The expression of CYP1A2 in liver microsomes from nizatidine treated was almost similar to control groups.In rat liver microsomal reconstituted system,nizatidine has no inhibitory effect on CYP1A2 activity compared with α-naphthoflavone that significantly inhibited phenacetin O-deethylation(IC_(50)=0.0306 μmol·L~(-1)).Conclusion Nizatidine has no inhibitory effect on rat CYP1A2 in vivo and in vitro.