Basic Research
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World J Gastroenterol. Jul 28, 2007; 13(28): 3841-3846
Published online Jul 28, 2007. doi: 10.3748/wjg.v13.i28.3841
Interaction of L-Arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats
Mehmet Cudi Tuncer, Hayrettin Ozturk, Huseyin Buyukbayram, Hulya Ozturk
Mehmet Cudi Tuncer, Dicle University, Medical School, Departments of Anatomy, Diyarbakir, Turkey
Hayrettin Ozturk, Abanty Izzet Baysal University, Medical School, Departments of Pediatric Surgery, Bolu, Turkey
Huseyin Buyukbayram, Dicle University, Medical School, Departments of Pathology, Diyarbakir, Turkey
Hulya Ozturk, Izzet Baysal Obstetric and Children Hospital, Department of Pediatric Surgery, Bolu, Turkey
Author contributions: All authors contributed equally to the work.
Correspondence to: Hayrettin Ozturk, MD, Associated Professor in Pediatric Surgery, Abant Izzet Baysal University, Medical School, Department of Pediatric Surgery, Bolu 14280, Turkey. ozturkhayrettin@hotmail.com
Telephone: +90-374-2534656- 4112 Fax: +90-374-2534615
Received: December 4, 2006
Revised: December 15, 2006
Accepted: December 20, 2006
Published online: July 28, 2007
Abstract

AIM: To investigate the role of Sonic hedgehog (Shh) on the course of liver ischemia and reperfusion (I/R) in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester (L-Arg) and up-regulation of Shh expression.

METHODS: A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Sham-control group (G1, n = 10): a sham operation was performed (except for liver I/R). I/R-untreated group (G2, n = 10): rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group (G3, n = 10): after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde (MDA) levels, and biochemical and histological evaluations were made.

RESULTS: Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGT) activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2, the hepatocytes were swollen with marked vacuolization. Group 3 rats showed well-preserved liver parenchyma, with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion. Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.

CONCLUSION: Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.

Keywords: Ischemia/reperfusion; Liver; Sonic hedgehog; L-Arginine-methyl ester