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    The effects of molsidomine on hypoxia inducible factor alpha and Sonic hedgehog in testicular ischemia/reperfusion injury in rats
    (Springer, 2009) Dokucu, Ali İhsan; Öztürk, Hülya; Öztürk, Hayrettin; Tuncer, Mehmet Cudi; Yılmaz, Fahri
    This study was designed to determine the effect of molsidomine (MO), a precursor of nitric oxide (NO) donor, on hypoxia inducible factor alpha (HIF-1 alpha) and Sonic hedgehog (Shh) levels considered to be involved in the development of testes ischemia/reperfusion (I-R) injury. Torsions were created by rotating ipsilateral testes 720A degrees in a clockwise direction for 6 h and 1-h detorsion of the testis was performed. A sham operation was performed in group 1 (control, n = 7). In group 2 (I-R/Untreated, n = 7), following 6 h of unilateral testicular torsion, 1-h detorsion of the testis was performed. No drug was given. In group 3 (I-R/MO), after performing the same surgical procedure as in group 2, a NO donor MO was given at the starting time of reperfusion. In group 4 (I-R/L-NAME), after performing the same surgical procedure as in group 2, L-NAME was given at the starting time of reperfusion. Testes malondialdehyde (MDA) levels were determined as well as examining the testes histologically. Treatment of rats with MO produced a significant reduction in the levels of MDA and histopathological score compared to testes I-R groups. The Sonic hedgehog (Shh) expression in the basement membrane of the tubuli seminiferi, and sertoli and germinal cells in testicular tissue, were greatly increased in the I-R/MO group compared to groups 1, 2 and 4. Additionally, the HIF-1 alpha expression in the interstitial spaces in testicular tissue were greatly increased in the I-R/MO group. The results suggest that MO has a protective effect against ischemia/reperfusion injury in rat testes and may affect Shh and HIF-1 alpha signaling pathway.
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    Interaction of L-Arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats
    (Baishideng Publishing Group Inc, 2007) Tuncer, Mehmet Cudi; Öztürk, Hayrettin; Büyükbayram, Hüseyin; Öztürk, Hülya
    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. Shamcontrol 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. 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. (c) 2007 WJG. All rights reserved.
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    Nitric oxide regulates expression of sonic hedgehog and hypoxia-inducible factor-1 alpha in an experimental model of kidney ischemia-reperfusion
    (Taylor & Francis Ltd, 2007) Öztürk, Hayrettin; Tuncer, Mehmet Cudi; Öztürk, Hülya; Büyükbayram, Hüseyin
    This study was designed to determine the effect of L-arginine on hypoxia inducible factor alpha (HIF-1 alpha) and Sonic hedgehog (Shh) levels considered to be involved in the development of ischemia/reperfusion (I/R) injury. Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 minutes of left renal ischeMia followed by 45 minutes of reperfusion. Group I were sham-operated animals; group 2, I-R/Untreated animals; and group 3, I-R/L-Arg-treated animals. Serum creatinine, blood urea nitrogen (BUN), and kidney malondialdehyde (MDA eve were determined as well as examining the kidneys histologicall The treatment of rats with L-Arg produced a significant reduction in the levels of BUN, creatinine, MDA, and histopathological score compared to renal I/R groups. The Shh expression in the tubulus epithelia were intensely increased in the I-R/L-Arg group when compared to that of the Sham-control and the I-R/ untreated groups. Additionally, the HIF-fix expression in the tubulus epithelia and the interstitial spaces were intensely increased in the I-R/L-Arg group. These findings suggest that NO reduces the renal dysfunction associated with I/R of the kidney and may act as a trigger to induce Shh and HIF-1 activity.