Protective effect of morin on the imipenem-induced nephrotoxicity in rabbits.
The present study investigated the protective effect of morin, a natural flavonoid, on the imipenem-induced nephrotoxicity in rabbits. Nephrotoxicity of imipenem was examined after the intravenous administrations of imipenem (200 mg/kg) to rabbits in the presence and the absence of morin (12, 25, 50 mg/kg, p.o.). Cytotoxicity of imipenem was also examined in the presence and the absence of morin (100 microM) by using MDCK cells overexpressing human organic anion transporter 1 and 3 (MDCK/hOAT1 or MDCK/hOAT3). Intravenous dosing of imipenem alone induced severe proximal tubular necrosis in rabbits, however, the concurrent use of morin (25 or 50 mg/kg, p.o.) significantly suppressed the histopathological damage in the kidney induced by imipenem. While imipenem was not cytotoxic in MDCK/hOAT1 cells over the tested concentrations up to 10 mM, it showed significant cellular toxicity with CC(50) of 0.77 mM in MDCK/hOAT3 cells, implying that OAT3 may involve more actively in the imipenem-induced nephrotoxicity. In addition, the cellular toxicity of imipenem decreased by approximately 20 folds in the presence of morin in MDCK/hOAT3 cells. In conclusion, the present study suggests that morin might be beneficial to reduce the nephrotoxicity of imipenem, at least in part, via the inhibition of OAT3-mediated renal excretion of imipenem.
Lim
Sung-Chul
SC
Department of Pathology, College of Medicine, Chosun University, Gwangju, Korea.
Im
Young-Bin
YB
Bae
Chun-Sik
CS
Han
Song Iy
SI
Kim
Se-Eun
SE
Han
Hyo-Kyung
HK
D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D005419:Flavonoids / Q000494:pharmacology*; D015378:Imipenem / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D014162:Transfection; D047309:Flavones
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005419:Flavonoids; D015378:Imipenem; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; C008548:morin; D047309:Flavones