| Sign In to gain access to subscriptions and/or personal tools. |
Species differences in hepatocyte induction of CYP1A1 and CYP1A2 by omeprazoleDepartment of Medicine, Section of Medical Toxicology, University of Colorado Health Sciences Center, Box B-146, 4200 E. 9th Avenue, Denver, Colorado 80262, USA
Department of Medicine, Section of Medical Toxicology, University of Colorado Health Sciences Center, Box B-146, 4200 E. 9th Avenue, Denver, Colorado 80262, USA
Department of Medicine, Section of Medical Toxicology, University of Colorado Health Sciences Center, Box B-146, 4200 E. 9th Avenue, Denver, Colorado 80262, USA
Department of Medicine, Section of Medical Toxicology, University of Colorado Health Sciences Center, Box B-146, 4200 E. 9th Avenue, Denver, Colorado 80262, USA
Department of Medicine, Section of Medical Toxicology, University of Colorado Health Sciences Center, Box B-146, 4200 E. 9th Avenue, Denver, Colorado 80262, USA 1 Omeprazole, a proton pump inhibitor therapeutically administered for the treatment of gastric ulcers, induces the expression of cytochromes P4501A1/2 (CYP1A1/2) through transcriptional activation mediated by the Ah (dioxin)-receptor. Primary cultures of hepatocytes isolated from rabbit, rat, mouse and human livers were compared for CYP1A1/2 mRNA inducibility by omeprazole (1 to 100 µM). 2 Primary cultures of human hepatocytes were the most sensitive to the inducing effects of omeprazole. Rabbit hepatocytes were the only other cells studied that showed induced CYP1A1/2 mRNA expression from a concentration lower than 100 µM (i.e., 10 µM). Rat hepatocytes were the least sensitive to omeprazole induction. The response of mouse hepatocytes to omeprazole treatment was variable, with CYP1A1/2 mRNA expression being induced in only two of the three cultures examined. 3 Differences in the time dependence of CYP1A1/2 mRNA expression were observed between species. In general, after treatment of hepatocytes with omeprazole the levels of CYP1A1 mRNA peaked prior to that of CYP1A2 mRNA. 4 Due to the interspecific variability of CYP1A mRNA inducibility by omeprazole, we conclude that human hepatocytes in culture are probably the only appropriate animal model for prediction of CYP1A induction in humans.
Key Words: CYP1A • omeprazole • hepatocytes • human
Human & Experimental Toxicology, Vol. 18, No. 2,
95-105 (1999) This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
|
 |
Sign In to gain access to subscriptions and/or personal tools.
