The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular Torsion Injury in Rats

Un, Harun; Bayır, Yasin; Halıcı, Zekai; Akpınar, Erol; Karakuş, Emre; Oral, Akgün; Ziypak, Tevfik; Selli, Jale

doi:10.1016/j.juro.2015.03.117

Cited by 13 publications

(14 citation statements)

References 26 publications

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“…Up to now, researchers have attempted various candidate to attenuate T/D‐induced testicular I/R injury and facilitate spermatogenesis . More recently, adipose tissue‐derived mesenchymal stem cells (AdMSCs) have been explored to be able to rescue testicular torsion‐induced germ cell injury and induce spermatogenesis in seminiferous tubules of busulfan‐induced azoospermic rat .…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Zhou

Song

et al. 2018

Stem Cells Translational Medicine

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Torsion‐detorsion (T/D)‐induced testicular injury may lead to male subfertility and even infertility. Stem cell therapy provides an alternative to attenuate testicular injury and promote spermatogenesis. Adipose‐derived stromal vascular fraction (SVF) can be acquired conveniently without in vitro expansion, which may avoid the potential risks of microbial contamination, xenogenic nutritional sources, etc., during cell culture. In this study, we investigate the protective effects of autologous uncultured SVF on testicular injury and spermatogenesis in a rat model of T/D. Animals were randomly divided into sham, T/D+ phosphate‐buffered saline, and T/D + SVF groups (18 rats in each group). SVF was isolated, labeled with lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine, and transplanted into T/D testis by local injection. At 3, 7, 14, and 28 days F surgery, testicular tissue and serum samples were harvested for histopathological, immunohistochemical, Western blot, and enzyme‐linked immunosorbent assays. Histopathological findings demonstrated severe injury in the testis with decreased Johnsen's score led by T/D, while uncultured SVF reduced testicular injury and elevated the decreased score. Injected SVF cells were mainly integrated into interstitial region and seminiferous tubules, enhanced the secretion of basic fibroblast growth factor and stem cell factor in the testis, contributed to the declining level of malondialdehyde and restoration of hormonal homeostasis, and then reduced the injury of Leydig cells and germ cells, as well as promoting spermatogenesis. Our findings demonstrated that autologous uncultured SVF could protect the testis from testicular ischemia‐reperfusion injury and promote spermatogenesis, which provide significant clinical implications for the prevention of infertility induced by testicular T/D. Stem Cells Translational Medicine 2019;8:383–391

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Zhou

Song

et al. 2018

Stem Cells Translational Medicine

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“…The antioxidant system removes the radicals that are produced in an increasing amount during I/R, and as the SOD enzyme is an effective antioxidant enzyme, SOD physiologically protects the cells against the harmful effects of the superoxide radicals. Studies have shown that SOD activity is reduced due to testis torsion and detorsion (Un et al., ). We examined SOD activity in the testis tissue and showed that SOD activity declined in T/D groups when compared to the healthy group and that this reduction occurred not only in the torsioned testis but also in the opposite testis.…”

Section: Discussionmentioning

confidence: 99%

“…The animals were anesthetised by an intraperitoneally injection of 25 mg/kg thiopental sodium. IR was applied for 2 hr, and the surgical procedures were performed as described previously (Un et al., ). Detorsion was then performed, the testicles were placed back into the scrotum, and the scrotum was closed by interrupted 4/0 silk sutures.…”

Section: Methodsmentioning

confidence: 99%

“…After the surgical procedures, approximately 100 mg of ground tissue (Un et al., ) was homogenised in 1 ml of phosphate‐buffered saline homogenate buffer in an Eppendorf tube using tissue lyser II and then centrifuged. SOD (Sun, Oberley, & Li, ), GSH (Sedlak & Lindsay, ) and MDA (Ohkawa, Ohishi, & Yagi, ) levels from each sample supernatant and standards were measured at room temperature in duplicate according to the modified methods of the ELISA reader, as described previously (Bulbuloglu et al., ).…”

Section: Methodsmentioning

confidence: 99%

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Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion

et al. 2016

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The purpose of this study was to examine potential long-term post-torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty-eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn- 1 month), (T/D+,Zn- 2 months), (T/D+,Zn- 3 months), (T/D+,Zn+ 1 months), (T/D+,Zn+ 2 months), (T/D+,Zn+ 3 months), have been used. Drug administration was carried out by adding 100 μg (0.016 ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically.

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“…The roles of angiotensin in the male reproductive tract include steroidogenesis regulation through Leydig cell inhibition by Ang II, alterations in epididymal contractility and sperm cell function (Leung & Sernia, ). Ang II, the main peptide of this system, is a well‐known oxidative stress inducer, which increases the production of ROS; therefore, blockade of RAS may reduce oxidative stress damage (Un et al., ). It was already reported that an AT1 receptor blocker, telmisartan, decreased the elevation of NO and attenuated the cadmium‐induced testicular toxicity in rats (Fouad & Jresat, ).…”

Section: Discussionmentioning

confidence: 99%

Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis

et al. 2016

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To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis.

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The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular Torsion Injury in Rats

Abstract: It appears that aliskiren protects the testis from ischemia-reperfusion damage by regulating inflammation and the oxidant-antioxidant balance via renin-angiotensin-aldosterone system inhibition.

Cited by 13 publications

References 26 publications

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion

Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis

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