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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalCell Biology and Toxicology
Volume25
Issue number3
DOIs
StatePublished - Jun 2009

Fingerprint

Epoxide Hydrolases
Cisplatin
lauric acid
Dialysis
Inbred C3H Mouse
Blood Urea Nitrogen
Intraperitoneal Injections
Acute Kidney Injury
Tumors
Esters
Blood
Kidney
Neoplasms
Therapeutics

Keywords

  • Cisplatin
  • Nephrotoxicity
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Cell Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Parrish, A. R., Chen, G., Burghardt, R. C., Watanabe, T., Morisseau, C., & Hammock, B. D. (2009). Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase. Cell Biology and Toxicology, 25(3), 217-225. https://doi.org/10.1007/s10565-008-9071-0

Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase. / Parrish, Alan R.; Chen, Gang; Burghardt, Robert C.; Watanabe, Takaho; Morisseau, Christophe; Hammock, Bruce D.

In: Cell Biology and Toxicology, Vol. 25, No. 3, 06.2009, p. 217-225.

Research output: Contribution to journalArticle

Parrish, AR, Chen, G, Burghardt, RC, Watanabe, T, Morisseau, C & Hammock, BD 2009, 'Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase', Cell Biology and Toxicology, vol. 25, no. 3, pp. 217-225. https://doi.org/10.1007/s10565-008-9071-0
Parrish, Alan R. ; Chen, Gang ; Burghardt, Robert C. ; Watanabe, Takaho ; Morisseau, Christophe ; Hammock, Bruce D. / Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase. In: Cell Biology and Toxicology. 2009 ; Vol. 25, No. 3. pp. 217-225.
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