MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid.

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Kugai M, Uchiyama K, Tsuji T, Yoriki H, Fukui A, Qin Y, Higashimura Y, Mizushima K, Yoshida N, Katada K, Kamada K, Handa O, Takagi T, Konishi H, Yagi N, Yoshikawa T, Shirasaka Y, Tamai I, Naito Y, Itoh Y

MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid.

Cell Physiol Biochem. 2013;32(4):942-50. doi: 10.1159/000354497. Epub 2013 Oct 1.

PubMed ID

24107783 [ View in PubMed

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Abstract

BACKGROUND/AIMS: Although the cytotoxicity of aspirin against the intestinal epithelium is a major clinical problem, little is known about its pathogenesis. We assessed the involvement of Multi Drug Resistance (MDR) 1 in intestinal epithelial cell injury caused by aspirin using MDR1 gene-transfected Caco2 cells. METHODS: Caco2 cells were treated with various concentrations of aspirin for 24 h. After treatment of Caco2 cells with verapamil, a specific inhibitor of MDR1, we assessed the extent of cell injury using a WST-8 assay at 24 h after aspirin-stimulation. We performed the same procedure in MDR1 gene-transfected Caco2 cells. To determine the function of MDR1 in the metabolism of aspirin, flux study was performed using (14)C-labeled aspirin. RESULTS: The level of aspirin-induced cell injury was higher in verapamil-treated Caco2 cells than in control cells and was less serious in MDR1-transfected Caco2 cells than in control vector-transfected cells. The efflux of (14)C-labeled aspirin was higher in verapamil-treated Caco2 cells than in control cells. CONCLUSION: These data suggest that aspirin effux occurs through the MDR1 transporter and that the MDR1 transporter is involved in the pathogenesis of aspirin-induced cell injury.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inducer Modulator	Details