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

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Acute Kidney Injury
Prostaglandins
Kidney
Reperfusion
Reperfusion Injury
Creatinine
Ischemia
15-deoxy-delta(12,14)-prostaglandin J2
cyclopentenone
Hexosaminidases
Prostaglandin D2
Wounds and Injuries
Nitric Oxide Synthase Type II
Intercellular Adhesion Molecule-1
Aspartate Aminotransferases
Interferons
Lipopolysaccharides
Urea
Wistar Rats
Nitric Oxide

Keywords

  • Renal function
  • Ischemia
  • Reperfusion
  • Prostaglandins
  • Rat

Cite this

Chatterjee, P. K., Patel, N. S. A., Cuzzocrea, S., Brown, P. A. J., Stewart, K. N., Mota-Filipe, H., ... 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
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. / The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 ameliorates ischemic acute renal failure. In: Cardiovascular Research. 2004 ; Vol. 61, No. 3. pp. 630-643.
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Chatterjee, PK, Patel, NSA, Cuzzocrea, S, Brown, PAJ, Stewart, KN, 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, vol. 61, no. 3, pp. 630-643. https://doi.org/10.1016/j.cardiores.2003.10.024

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

In: Cardiovascular Research, Vol. 61, No. 3, 02.2004, p. 630-643.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 ameliorates ischemic acute renal failure

AU - Chatterjee, P.K.

AU - Patel, N.S.A.

AU - Cuzzocrea, S.

AU - Brown, P.A.J.

AU - Stewart, K.N.

AU - Mota-Filipe, H.

AU - Britti, D.

AU - Eberhardt, W.

AU - Pfeilschifter, J.

AU - Thiemermann, C.

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

KW - Renal function

KW - Ischemia

KW - Reperfusion

KW - Prostaglandins

KW - Rat

U2 - 10.1016/j.cardiores.2003.10.024

DO - 10.1016/j.cardiores.2003.10.024

M3 - Article

VL - 61

SP - 630

EP - 643

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -