|
KMID : 0043320080310081060
|
|
Archives of Pharmacal Research
2008 Volume.31 No. 8 p.1060 ~ p.1065
|
|
|
Protective Effect of Morin on the Imipenem-induced Nephrotoxicity in Rabbits
|
|
Lim Sung-Chul
Im Young-Bin
Bae Chun-Sik
Han Song-Iy
Kim Se-Eun
Han Hyo-Kyung
|
|
|
Abstract
|
|
|
|
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 () 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 of 0.77 mM in MDCK/hOAT3 cells, implying that OAT3 may involve more actively in the imipeneminduced 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.
|
|
|
KEYWORD
|
|
|
Imipenem, Morin, Nephrotoxicity, Organic anion transporters, Rabbit
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|