Downregulated expression of organic anion transporting polypeptide (Oatp) 2b1 in the small intestine of rats with acute kidney injury

• Published in: Drug metabolism and pharmacokinetics Vol. 40; p. 100411
• Main Authors: Takeda, Fuyo, Oda, Masako, Terasaki, Masaru, Kubota, Atsuhito, Asada, Keita, Ichimura, Yuichi, Kojima, Hiroyuki, Saitoh, Hiroshi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2021
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Animals; Cisplatin; Intestine, Small; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Organic anion-transporting polypeptide 2b1; Pravastatin; Rat small intestine; Rats; Organic anion-transporting polypeptide 2b1; Pravastatin; Rat small intestine; Acute kidney injury; Cisplatin
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2021.100411

The expression of transporters on the apical and basal membranes of renal tubular cells is modulated under acute kidney injury (AKI). However, little is known about alterations in non-renal transporters in the tissues other than the kidney under AKI situation. This study aimed to assess the modulation of organic anion transporting polypeptide (Oatp) 1a2 and Oatp2b1 expression/function in the small intestine of rats with drug-induced AKI. AKI was induced by intraperitoneal administration of cisplatin at a dose of 5 mg/kg. On day 3 after cisplatin administration, morphological changes in the small intestine, Oatp1a2 and Oatp2b1 expression, and absorption of pravastatin and theophylline were evaluated. Non-negligible atrophy was observed in the jejunum and ileum of the AKI rats. However, the absorption of theophylline was not affected. While intestinal Oatp2b1 expression was markedly decreased in the AKI rats, no alteration was observed in Oatp1a2 expression. The plasma levels of pravastatin after intraluminal administration declined significantly in the AKI rats. However, no such decline was observed after intravenous administration. This study suggested that the responses of intestinal Oatps to experimentally induced AKI was not unidirectional and that pravastatin absorption was governed more potently by Oatp2b1 than by Oatp1a2 in the rat intestine.