Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/21228
Título: The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) ameliorates ischemic acute renal failure
Autor: Chatterjee, PK
Patel, NSA
Cuzzocrea, S
Brown, PAJ
Stewart, KN
Mota-Filipe, H
Britti, D
Eberhardt, W
Pfeilschifter, J
Thiemermann, C
Palavras-chave: Cardiac & Cardiovascular Systems
Data: 2004
Citação: CARDIOVASCULAR RESEARCH. - Vol. 61, n. 3 (FEB 15 2004), p. 630-643
Resumo: 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.
URI: http://hdl.handle.net/10451/21228
DOI: http://dx.doi.org/10.1016/j.cardiores.2003.10.024
ISSN: 0008-6363
Aparece nas colecções:FF - Produção Científica 2000-2009

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