title: The effects of molsidomine on hypoxia inducible factor alpha and Sonic hedgehog in testicular ischemia/reperfusion injury in rats.
abstract: This study was designed to determine the effect of molsidomine (MO), a precursor of nitric oxide (NO) donor, on hypoxia inducible factor alpha (HIF-1alpha) 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 720 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-1alpha 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-1alpha signaling pathway.
authors.affiliation: Department of Pediatric Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ali Ihsan
authors.initials: AI
authors.lastname: Dokucu
authors.forename: Hulya
authors.initials: H
authors.lastname: Ozturk
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Ozturk
authors.forename: Mehmet Cudi
authors.initials: MC
authors.lastname: Tuncer
authors.forename: Fahri
authors.initials: F
authors.lastname: Yilmaz
mesh_terms: D000818:Animals; D053823:Hedgehog Proteins / Q000096:biosynthesis* / Q000187:drug effects*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000187:drug effects*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D013737:Testis / Q000098:blood supply*
chemical_list: D053823:Hedgehog Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008981:Molsidomine
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