Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, in rats

Authors: Naito Y.1; Takagi T.1; Uchiyama K.1; Handa O.1; Tomatsuri N.1; Imamoto E.1; Kokura S.1; Ichikawa H.1; Yoshida N.1; Yoshikawa T.1

Source: Redox Report, Volume 7, Number 5, October 2002 , pp. 294-299(6)

Publisher: Maney Publishing

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Abstract:

Neutrophil activation and tumor necrosis factor-alpha (TNF-alpha) induction play a critical role in ischemia-reperfusion-induced intestinal inflammation. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate reperfusion-induced intestinal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression. Intestinal damage was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 30 min followed by reperfusion. Reperfusion after 30 min ischemia resulted in an increase in luminal protein concentrations with levels reaching a maximum after 60 min of reperfusion. In contrast, pretreatment with pioglitazone 2 h before ischemia inhibited the increase in luminal protein concentrations after 60 min reperfusion in a dose-dependent manner (1-30 mg/kg). The increase in tissue-associated myeloperoxidase activity, an index of neutrophil infiltration, after reperfusion was significantly inhibited by pretreatment with pioglitazone. Pioglitazone also inhibited increases in intestinal TNF-alpha protein and mRNA expression determined by ELISA and RT-PCR, respectively. In conclusion, activation of PPAR-gamma may represent a novel approach to the treatment of intestinal inflammation induced by ischemia-reperfusion.

Document Type: Regular paper

DOI: 10.1179/135100002125000983

Affiliations: 1: First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

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