Attenuation of Cisplatin Nephrotoxicity by the Soluble Epoxide Hydrolase Inhibitor nbAUDA Conference Paper uri icon

abstract

  • Cisplatin is a highly effective chemotherapeutic agent against many tumors, but it also a potent nephrotoxicant. Given that there have been no significant advances in our ability to clinically manage acute renal failure since the advent of dialysis, the development of novel strategies to ablate nephrotoxicity would represent a significant development. In this study, we investigated the ability of an inhibitor of soluble epoxide hydrolase (sEH), nbutyl ester of 12(3adamantan1ylureiido)dodecanoic acid (nbAUD), to attenuate cisplatininduced nephrotoxicity. nbAUDA is quickly converted to AUDA and produces higher blood levels of AUDA than administration of AUDA itself. Administration of 40 mg/kg of nbAUDA to C3H mice every 24 hr resulted in elevated levels of AUDA; this protocol was also associated with attenuation of cisplatininduced nephrotoxicity as assessed by BUN levels and histological evaluation of kidneys. This is the first report of the use of sEH inhibitors to protect against acute nephrotoxicity and suggest a therapeutic potential of these compounds.

published proceedings

  • FASEB JOURNAL

author list (cited authors)

  • Akintola, A. D., Parrish, A., Burghardt, R. C., Watanabe, T., Morisseau, C., & Hammock, B. D.

citation count

  • 0

complete list of authors

  • Akintola, Adebayo D||Parrish, Alan||Burghardt, Robert C||Watanabe, Takaho||Morisseau, Christophe||Hammock, Bruce D

publication date

  • March 2008

publisher