Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver
| Autor: | Kaori Kuwayama, Takahiro Koizumi, Ken Iseki, Jiro Ogura, Yusuke Terada, Masaki Kobayashi, Shunichi Sasaki, Takashi Tsujimoto, Hiroaki Yamaguchi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Organic anion transporting polypeptide
Male Xanthine Oxidase Pharmaceutical Science Organic Anion Transporters Endogeny Pharmacology medicine.disease_cause Cell Line chemistry.chemical_compound Pharmacokinetics In vivo Cell Line Tumor medicine Animals Humans RNA Messenger Rats Wistar Xanthine oxidase Pravastatin chemistry.chemical_classification Reactive oxygen species biology Hydrogen Peroxide Inosine Rats Organic anion-transporting polypeptide Oxidative Stress chemistry Liver biology.protein Hepatocytes Lipid Peroxidation Oxidative stress medicine.drug |
| Zdroj: | International journal of pharmaceutics. 458(2) |
| ISSN: | 1873-3476 |
| Popis: | Reactive oxygen species (ROS) have physiological function and involve alteration of physical state. However, it is not clear effect of oxidative stress on pharmacokinetics. Organic anion transporting polypeptides (human: OATPs, rodent: Oatps) are important for uptake of endogenous and exogenous compounds into hepatocytes. Thus, alteration of OATPs/Oatps expression level may affect pharmacokinetics of various drugs. In this study, we investigated the alteration of OATPs/Oatps expression levels and function by oxidative stress, and the effect of alteration of those on pharmacokinetics of a typical OATPs/Oatps substrate pravastatin. OATPs/Oatps expression levels and function were altered by H2O2-induced oxidative stress in in vitro experiments. The alteration of Oatps expression by oxidative stress also occurred in in vivo experiments. Oatp1a1, Oatp1a4 and Oatp1b2 expression in the liver were decreased in rats fed powdery diet containing 2% inosine, which induces oxidative stress through activation of xanthine oxidase, for 1 day. The decrease in Oatps expression levels by oxidative stress caused the suppression of pravastatin uptake to the liver, and resulted in high plasma concentration of pravastatin and low biliary excretion. In conclusion, oxidative stress induces alteration of OATPs/Oatps expression and function in hepatocytes, resulting in alteration of pharmacokinetics of their substrates. (C) 2013 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect