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Protective effect of endogenous PPAR against acute gastric mucosal lesions associated with ischemia-reperfusion

¹Department of Pharmacology, School of Dentistry, Osaka University, Osaka 566-0871; ²Gastroenterology Division, Brigham and Women's Hospital and Harvard Medical School, Boston 02115; ³Gastroenterology Division, Yokohama City University, Yokohama 236-0004; ⁴Department of Internal Medicine, University of Tokyo, Tokyo 113-0033; and ⁵Section of Gastroenterology, Boston University School of Medicine, Boston, Massachusetts 02118; and ⁶Pathology Division, National Institute of Health, Tokyo, Japan 162-8640

Submitted 17 December 2003 ; accepted in final form 11 March 2004

Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor- (PPAR), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPAR ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPAR-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPAR ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPAR-deficient mice was more severe than that observed in wild-type mice. Administration of the PPAR ligand significantly inhibited the upregulation of TNF-, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPAR plays an important role in the pathogenesis of I/R-associated injury in the stomach.

peroxisome proliferator-activated receptor- nitrotyrosine; ICAM-1

This article has been cited by other articles:

				M. Abdelrahman, A. Sivarajah, and C. Thiemermann Beneficial effects of PPAR-{gamma} ligands in ischemia-reperfusion injury, inflammation and shock Cardiovasc Res, March 1, 2005; 65(4): 772 - 781. [Abstract] [Full Text] [PDF]