Cell Biology and Toxicology

, Volume 25, Issue 3, pp 217–225

Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase

  • Alan R. Parrish
  • Gang Chen
  • Robert C. Burghardt
  • Takaho Watanabe
  • Christophe Morisseau
  • Bruce D. Hammock
Article

Abstract

Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it is 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), n-butyl ester of 12-(3-adamantan-1-yl-ureiido)-dodecanoic acid (nbAUDA), to attenuate cisplatin-induced nephrotoxicity. nbAUDA is quickly converted to AUDA and results in maintenance of high AUDA levels in vivo. Subcutaneous administration of 40 mg/kg of nbAUDA to C3H mice every 24 h resulted in elevated blood levels of AUDA; this protocol was also associated with attenuation of nephrotoxicity induced by cisplatin (intraperitoneal injection) 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 suggests a therapeutic potential of these compounds.

Keywords

Cisplatin Nephrotoxicity Soluble epoxide hydrolase 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Alan R. Parrish
    • 1
  • Gang Chen
    • 1
  • Robert C. Burghardt
    • 2
  • Takaho Watanabe
    • 3
    • 4
  • Christophe Morisseau
    • 4
  • Bruce D. Hammock
    • 4
  1. 1.Department of Systems Biology and Translational Medicine, College of MedicineTexas A&M Health Science CenterCollege StationUSA
  2. 2.Department of Veterinary Integrated Biosciences, College of Veterinary MedicineTexas A&M UniversityCollege StationUSA
  3. 3.Food and Drug Safety CenterHatano Research InstituteHadanoJapan
  4. 4.Department of Entomology and UCD Cancer CenterUniversity of California at DavisDavisUSA

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