Protective effect of morin on the imipenem-induced nephrotoxicity in rabbits

Sung Chul Lim, Young Bin Im, Chun Sik Bae, Song Iy Han, Se Eun Kim, Hyo Kyung Han

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21 Scopus citations

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 (100 μM) 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 CC50 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.

Original languageEnglish
Pages (from-to)1060-1065
Number of pages6
JournalArchives of Pharmacal Research
Volume31
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Imipenem
  • Morin
  • Nephrotoxicity
  • Organic anion transporters
  • Rabbit

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