Kousei Ito — Page 2 | PubMed Health

PubMed2002

Plasma retinol binding protein for monitoring the acetaminophen-induced hepatotoxicity.

Retinol-binding protein (RBP) is a specific transport protein which carries retinol in the circulation. RBP concentration in plasma and liver of rats following a large dose of acetaminophen (APAP) intraperitoneally was examined. The RBP concentration in plasma decreased significantly at 12 hr after the APAP administration, while the plasma albumin concentration was affected a little. Western blot and northern blot analyses showed marked changes in RBP but not in albumin. Thus, RBP was suggested to be more sensitive for the acute drug-induced hepatotoxicity than albumin. The decrease of RBP concentration in plasma was suggested to be caused by the dysfunction of RBP synthesis in the liver.

Journal Article↗

PubMed2001

Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2).

Human organic anion transporting polypeptide 2 (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2) play important roles in the vectorial transport of organic anions across hepatocytes. In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and apical membranes, respectively. The basal-to-apical transport of 17 beta estradiol 17 beta-d-glucuronide (E(2)17 beta G), pravastatin, and leukotriene C(4) (LTC(4)), which are substrates of OATP2 and MRP2, was significantly higher than that in the opposite direction in the double-transfected cells. Such vectorial transport was also observed for taurolithocholate sulfate, which is transported by rat oatp1 and Mrp2. The K(m) values of E(2)17 beta G and pravastatin for the basal-to-apical flux were 27.9 and 24.3 microm, respectively, which were comparable with those reported for OATP2. Moreover, the MRP2-mediated export of E(2)17 beta G across the apical membrane was not saturated. In contrast, basal-to-apical transport of estrone-3-sulfate and dehydroepiandrosterone sulfate, which are significantly transported by OATP2, but not by MRP2, was not stimulated by MRP2 expression. The double-transfected MDCK II monolayer expressing both OATP2 and MRP2 may be used to analyze the hepatic vectorial transport of organic anions and to screen the transport profiles of new drug candidates.

Animals↗