Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K/AKT pathway in mouse model of testicular torsion-detorsion

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.

Salidroside Exerts Beneficial Effect on Testicular Ischemia-Reperfusion Injury in Rats

“…These indicators well showed testicular ischemia-reperfusion injury (Figures 3 and 4 ). They have been widely used in testicular ischemia-reperfusion injury studies [ 86 – 88 ]. Testicular section stained with Masson trichrome is usually used to quantify collagen accumulation as a marker of fibrosis [ 89 ].…”

Vanillin and pentoxifylline ameliorate isoproterenol-induced myocardial injury in rats via the Akt/HIF-1α/VEGF signaling pathway

“…Our findings are in accordance with Dhulqarnain et al who reported that PTX improved spermatogenic cell survival in mice by activating the Akt signaling pathway. 93…”

“…Our findings are in accordance with Dhulqarnain et al who reported that PTX improved spermatogenic cell survival in mice by activating the Akt signaling pathway. 93 Pentoxifylline treatment led to significant improvements in cardiac structure and function. This was evident by the marked decrease in cardiac hypertrophy and serum levels of CK-MB, LDH and troponin-I.…”

Treatment of Poor Sperm Quality and Erectile Dysfunction With Oral Pentoxifylline: A Systematic Review

“…However, Schramm et al reported that the maximum PTX concentration in seminal plasma was only 75 ng/ml (0.3 μM) ( Schramm and Hinze, 1980 ). Recent two in vitro studies demonstrated the protective impact of PTX on spermatogenesis in mice models with both concentration levels higher than 0.3 μM ( Dhulqarnain et al, 2021 ; Malekzadeh et al, 2021 ). 3) Increased blood perfusion and reduced blood viscosity in testes and epididymis: Pozor and his colleagues confirmed that PTX-treated stallions had significantly higher total arterial blood flow rate than controls, delaying the seasonal decrease of testicular perfusion, without sperm quality and total sperm volume improved ( Pozor et al, 2011 ).…”