{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:13:09Z","timestamp":1763640789119,"version":"3.28.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2001,6,1]],"date-time":"2001-06-01T00:00:00Z","timestamp":991353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acute hepatic failure was induced experimentally in rats by intraperitoneal injection of 2.5 mL kg\u22121 carbon tetrachloride (CCl4), and the effects on the expression and function of P-glycoprotein in the liver, kidney and brain were evaluated. The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate). In rats with acute hepatic failure, the hepatic P-glycoprotein concentration increased 1.5-fold and the ATP concentration decreased to approximately 40% that in control rats. In contrast, P-glycoprotein concentrations in the kidney and brain and ATP concentrations in the kidney remained unchanged. The in-vivo P-glycoprotein function in these tissues was suppressed as evaluated by biliary and renal secretory clearances and brain distribution of rhodamine 123, a P-glycoprotein substrate. These findings suggest that factors other than P-glycoprotein concentration are involved in the systemic suppression of P-glycoprotein function in diseased rats. In Caco-2 cells, plasma collected from CCl4-treated rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of rhodamine 123 than that from control rats, suggesting the accumulation of an endogenous P-glycoprotein substrate\/inhibitor in the plasma of diseased rats. In fact, the plasma concentration of corticosterone, an endogenous P-glycoprotein substrate, increased 2-fold in CCl4-treated rats compared with control rats. It was demonstrated that P-glycoprotein function is systemically suppressed in rats with CCl4-induced acute hepatic failure, not only in the target organ (liver), but also in other organs (kidney and brain), although the P-glycoprotein concentration remained unchanged in the kidney and brain, and increased in the liver. In the systemic suppression of the P-glycoprotein function in the diseased state, the alteration of plasma concentrations or components of endogenous P-glycoprotein-related compounds, such as corticosterone, would likely be involved.<\/jats:p>","DOI":"10.1211\/0022357011776036","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"873-881","source":"Crossref","is-referenced-by-count":33,"title":["Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure"],"prefix":"10.1093","volume":"53","author":[{"given":"Zhao-Hui","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruo","family":"Murakami","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuko","family":"Okochi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoko","family":"Yumoyo","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Nagai","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikihisa","family":"Takano","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,6,1]]},"reference":[{"key":"2024103110060274900_cit1","first-page":"539","article-title":"Importance of cell kinetics rhythmicity for the control of cell proliferation and carcinogenesis in rat liver (review)","volume":"9","author":"Barbason","year":"1995","journal-title":"In Vivo"},{"key":"2024103110060274900_cit2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1055\/s-2007-1003295","article-title":"New mechanism of hormone secretion: MDR-like gene products and extrusion pumps for hormones","volume":"24","author":"Becker","year":"1992","journal-title":"Horm. 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