The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2 ameliorates ischemic acute renal failure

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

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Abstract

Objective: Here we investigate the effects of the endogenous prostaglandin D-2 metabolite 15-deoxy-Delta(12,14)-prostaglandin J(2), 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-Delta(12,14)-prostaglandin J(2) (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Delta(12,14)-prostaglandin J(2) 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-beta-D-glucosaminidase, aspartate aminotransferase (ASP) and gamma-glutamyltransferase (gamma-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Delta(12,14)-prostaglandin J(2) also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Delta(12,14)-prostaglandin J, markedly reduced the expression of inducible nitric oxide synthase (NOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis Of IkappaB-alpha degradation revealed that 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited the activation of nuclear factor (NF)-kappaB in renal cells. Subsequently, 15d-PGJ(2) 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-gamma and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Delta(12,14)-prostaglandin J(2) significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-kappaB. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)630-643
Number of pages14
JournalCardiovascular Research
Volume61
Issue number3
DOIs
Publication statusPublished - 15 Feb 2004

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Acute Kidney Injury
Prostaglandins
Kidney
Reperfusion
Reperfusion Injury
Creatinine
Ischemia
15-deoxy-delta(12,14)-prostaglandin J2
cyclopentenone
Prostaglandins D
D-Aspartic Acid
Acetylglucosaminidase
gamma-Glutamyltransferase
Wounds and Injuries
Nitric Oxide Synthase Type II
Intercellular Adhesion Molecule-1
Aspartate Aminotransferases
Interferon-gamma
Lipopolysaccharides
Urea

Keywords

  • renal function
  • ischemia
  • reperfusion
  • prostaglandins
  • rat
  • activated-receptor-gamma
  • NF-kappa-B
  • PPAR-gamma
  • nitric oxide
  • mesangial cells
  • reperfusion injury
  • chronic inflammation
  • in-vivo
  • expression

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-Delta(12,14)-prostaglandin J2 ameliorates ischemic acute renal failure. Cardiovascular Research, 61(3), 630-643. https://doi.org/10.1016/j.cardiores.2003.10.024

The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2 ameliorates ischemic acute renal failure. / Chatterjee, P K ; Patel, N S A ; Cuzzocrea, S ; Brown, P A J ; Stewart, Keith Nicol; Mota-Filipe, H ; Britti, D ; Eberhardt, W ; Pfeilschifter, J ; Thiemermann, C .

In: Cardiovascular Research, Vol. 61, No. 3, 15.02.2004, p. 630-643.

Research output: Contribution to journalArticle

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-Delta(12,14)-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
Chatterjee, P K ; Patel, N S A ; Cuzzocrea, S ; Brown, P A J ; Stewart, Keith Nicol ; Mota-Filipe, H ; Britti, D ; Eberhardt, W ; Pfeilschifter, J ; Thiemermann, C . / The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2 ameliorates ischemic acute renal failure. In: Cardiovascular Research. 2004 ; Vol. 61, No. 3. pp. 630-643.
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abstract = "Objective: Here we investigate the effects of the endogenous prostaglandin D-2 metabolite 15-deoxy-Delta(12,14)-prostaglandin J(2), 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-Delta(12,14)-prostaglandin J(2) (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Delta(12,14)-prostaglandin J(2) 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-beta-D-glucosaminidase, aspartate aminotransferase (ASP) and gamma-glutamyltransferase (gamma-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Delta(12,14)-prostaglandin J(2) also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Delta(12,14)-prostaglandin J, markedly reduced the expression of inducible nitric oxide synthase (NOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis Of IkappaB-alpha degradation revealed that 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited the activation of nuclear factor (NF)-kappaB in renal cells. Subsequently, 15d-PGJ(2) 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-gamma and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Delta(12,14)-prostaglandin J(2) significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-kappaB. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.",
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T1 - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-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, Keith Nicol

AU - Mota-Filipe, H

AU - Britti, D

AU - Eberhardt, W

AU - Pfeilschifter, J

AU - Thiemermann, C

PY - 2004/2/15

Y1 - 2004/2/15

N2 - Objective: Here we investigate the effects of the endogenous prostaglandin D-2 metabolite 15-deoxy-Delta(12,14)-prostaglandin J(2), 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-Delta(12,14)-prostaglandin J(2) (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Delta(12,14)-prostaglandin J(2) 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-beta-D-glucosaminidase, aspartate aminotransferase (ASP) and gamma-glutamyltransferase (gamma-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Delta(12,14)-prostaglandin J(2) also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Delta(12,14)-prostaglandin J, markedly reduced the expression of inducible nitric oxide synthase (NOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis Of IkappaB-alpha degradation revealed that 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited the activation of nuclear factor (NF)-kappaB in renal cells. Subsequently, 15d-PGJ(2) 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-gamma and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Delta(12,14)-prostaglandin J(2) significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-kappaB. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

AB - Objective: Here we investigate the effects of the endogenous prostaglandin D-2 metabolite 15-deoxy-Delta(12,14)-prostaglandin J(2), 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-Delta(12,14)-prostaglandin J(2) (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Delta(12,14)-prostaglandin J(2) 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-beta-D-glucosaminidase, aspartate aminotransferase (ASP) and gamma-glutamyltransferase (gamma-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Delta(12,14)-prostaglandin J(2) also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Delta(12,14)-prostaglandin J, markedly reduced the expression of inducible nitric oxide synthase (NOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis Of IkappaB-alpha degradation revealed that 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited the activation of nuclear factor (NF)-kappaB in renal cells. Subsequently, 15d-PGJ(2) 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-gamma and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Delta(12,14)-prostaglandin J(2) significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-kappaB. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

KW - renal function

KW - ischemia

KW - reperfusion

KW - prostaglandins

KW - rat

KW - activated-receptor-gamma

KW - NF-kappa-B

KW - PPAR-gamma

KW - nitric oxide

KW - mesangial cells

KW - reperfusion injury

KW - chronic inflammation

KW - in-vivo

KW - expression

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 -