Interaction of L-arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats.
OBJECTIVE
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 gamma-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.


CONCLUSIONS
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.
Dicle University, Medical School, Departments of Anatomy, Diyarbakir, Turkey.
Mehmet-Cudi
MC
Tuncer
Hayrettin
H
Ozturk
Huseyin
H
Buyukbayram
Hulya
H
Ozturk
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053823:Hedgehog Proteins / Q000378:metabolism*; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D015854:Up-Regulation
D053823:Hedgehog Proteins; D020030:Nitric Oxide Donors; C026512:arginine methyl ester; D001120:Arginine