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.

Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death

“…Several studies have been performed to reveal the protective effects of antioxidants on testicular tissue. Protective effects of molsidomine against ischaemia/reperfusion injury (Dokucu et al, 2009) and melatonin against damage caused by intermittent hypobaric hypoxia (Hartley et al, 2009) have been shown. Several lines of experimental evidence support the protective effect of erdosteine on different organs.…”

Sonic Hedgehog Protects Cortical Neurons Against Oxidative Stress

“…The effectiveness of SHH and GLI1 gene therapy in experimental Parkinson's disease suggests that SHH signaling may protect the nigrostriatal dopaminergic cells selectively and could be used for the treatment of neurodegeneration [4]. Some researches have reported that the expression levels of SHH signal components increase during ischemia in some tissue such as myocardium, somatic muscles, testis, and liver [5][6][7][8]. SHH expression is also found up-regulated in neurons during ischemia/hypoxia, and it appears to modulate proliferation of neural progenitor cells [9].…”

Beneficial effects of (−)-epigallocatechin gallate on ischemia-reperfusion testicular injury in rats

“…The ability of several antioxidants including vitamins E and C, selenium, SOD, and catalase to prevent testicular injury in I/R model animals has been investigated [4]. The following compounds have also been tested in models of testicular I/R: melatonin [16,17], steroid [17], allopurinol [5], trapidil [1,18], propofol [19], zinc aspirate [20], taurine [21], vascular endothelial growth factor [22], epidermal growth factor [23], cyclosporine-A and FK 506 [2], α-lipoic acid [24], molsidomine [25], trimetazidine [3], raxofelast [12], vasoactive intestinal peptide [13], platelet-activating factor antagonist [14], nonsteroidal anti-inflammatory drugs [11,26], garlic extract [27], Lomodex-MgSO 4 [28], erdosteine [29], resveratrol [30], verapamil [31], ethyl pyruvate [32], caffeic acid phenethyl ester [33], and sulfasalazine [34]. However, none of them have found routine clinical application [2,10].…”

“…Although some investigators have also studied the right testis [2,4,13,[24][25][26]30,32], the left [1,3,[10][11][12][16][17][18][19][20][21][22]27,33,34,39,41] seems to be more commonly studied. Testicular torsion clinically occurs more often in the left testis [53].…”