The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 ameliorates ischemic acute renal failure

P.K. Chatterjee, N.S.A. Patel, S. Cuzzocrea, P.A.J. Brown, K.N. Stewart, H. Mota-Filipe, D. Britti, W. Eberhardt, J. Pfeilschifter, C. Thiemermann

Research output: Contribution to journalArticle

Abstract

Objective: Here we investigate the effects of the endogenous prostaglandin D2 metabolite 15-deoxy-Δ12,14-prostaglandin J2, on the renal dysfunction and injury caused by ischemia/reperfusion of the kidney. Methods: Male Wistar rats, subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h, were administered 15-deoxy-Δ12,14-prostaglandin J2 (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Δ12,14-prostaglandin J2 significantly reduced (i) renal and tubular dysfunction (serum urea and creatinine levels, creatinine clearance, fractional excretion of Na+ (FENa)), (ii) tubular and reperfusion-injury (urinary N-acetyl-β-Image-glucosaminidase, aspartate aminotransferase (ASP) and γ-glutamyltransferase (γ-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Δ12,14-prostaglandin J2 also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Δ12,14-prostaglandin J2 markedly reduced the expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis of IκB-α degradation revealed that 15-deoxy-Δ12,14-prostaglandin J2 inhibited the activation of nuclear factor (NF)-κB in renal cells. Subsequently, 15d-PGJ2 was able to significantly reduce nitric oxide production during renal ischemia/reperfusion and by primary cultures of rat proximal tubular (PT) cells incubated with interferon-γ and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Δ12,14-prostaglandin J2 significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-κB.
Original languageEnglish
Pages (from-to)630-643
Number of pages14
JournalCardiovascular Research
Volume61
Issue number3
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Renal function
  • Ischemia
  • Reperfusion
  • Prostaglandins
  • Rat

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    Chatterjee, P. K., Patel, N. S. A., Cuzzocrea, S., Brown, P. A. J., Stewart, K. N., Mota-Filipe, H., Britti, D., Eberhardt, W., Pfeilschifter, J., & Thiemermann, C. (2004). The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 ameliorates ischemic acute renal failure. Cardiovascular Research, 61(3), 630-643. https://doi.org/10.1016/j.cardiores.2003.10.024