Abstract
Testicular torsion-detorsion results in enhanced formation of free radicals which contribute to the pathophysiology of testicular tissue damage. Recent reports have identified protective role of pentoxifylline (PTX) against free radicals. Thus, we determined the protective effect of pentoxifylline against testicular damage in mouse model of testicular torsion-detorsion.Twenty (6 weeks old) male mice were divided into 4 groups of 5 animals each namely: Control (sham operated group), T1 (Torsion-detosion + single dose 100 mg/kg PTX, T2 (torsion-detorsion + 20 mg/kg PTX for 2 weeks and T/D (torsion-detorsion only). Animals in T1, T2 and T/D groups underwent 2 h of testicular torsion with the left testes rotated 720° (clockwisely) followed by 30 min of detorsion. After detorsion, drug administration was done intraperitoneally. The left testes of all the animals were excised on the 35th day after torsion-detortion for histopathological and biochemical assay. Histomorphological analysis of the seminiferous tubules showed that there were significant increase (P < 0.01 or 0.05) in the mean seminiferous tubule diameter, Johnson score and germ cells of animals in Control and T1 compared to T2 and T/D with no significant difference (P > 0.05) in testes weight, sertoli, leydig and myoid cells in all groups. IHC results showed significant increase (P < 0.01 or 0.05) in id4 and scp3 protein markers in Control, T1 and T2 compared to T/D. Oxidative stress analysis revealed that Pentoxifylline significantly increased (P < 0.01 or 0.05) the level of SOD, catalase, mRNA expression of akt and pi3k genes but significantly suppress (P < 0.01 or 0.05) MDA and Caspase-3 level in Control, T1 and T2 compared to T/D. Pentoxifylline could be used as an adjunct therapy to surgery in the treatment of torsion-detorsion related testicular injury, However, Further studies are needed to evaluate the effects of pentoxifylline on testicular torsion.
Highlights
Testicular torsion is a urological emergency and a painful condition commonly affecting new born, children and adolescent boys that must be rapidly treated to avoid permanent damage to the testes [1]
Oxidative stress is implicated in ischemia-reperfusion mediated testicular damage which may be supported by the sudden induction of lipid peroxidation and the concomitant suppression of endogenous antioxidant activities including superoxide dismutase (SOD), catalase and glutathione peroxidase [5], it has been shown that these free radicals have beneficial effects in sperm physiology such as sperm maturation and capacitation [6]
Animals in T2 group have seminiferous tubules histoarchitecture similar to T/D group characterized by distorted seminiferous tubule epithelium and few germ cells (Figure 1C)
Summary
Testicular torsion is a urological emergency and a painful condition commonly affecting new born, children and adolescent boys that must be rapidly treated to avoid permanent damage to the testes [1]. In a study by Taneli et al, it was shown that prolonged torsion lead to testicular ischemia with high levels of oxidative stress in the ipsilateral testes associated with nitric oxide (NO) and hydrogen peroxide (H2O2) production, increased generation of lipid peroxide, isoprostane aggregation, decreased antioxidant enzymes level and increased rate of mitochondria-mediated apoptosis in the germ cell line [2]. Oxidative stress is implicated in ischemia-reperfusion mediated testicular damage which may be supported by the sudden induction of lipid peroxidation and the concomitant suppression of endogenous antioxidant activities including superoxide dismutase (SOD), catalase and glutathione peroxidase [5], it has been shown that these free radicals have beneficial effects in sperm physiology such as sperm maturation and capacitation [6]. While torsion and detorsion resulted to ischemia and reperfusion injury respectively, detorsion is the main source of free radical formation and lipid peroxidation damage [7]
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