Torsion Detorsion Research Articles

Costunolide, an effective agent against oxidative damage, apoptosis and autophagy in the ovarian torsion/detorsion model

Aim This study assessed the efficacy of costunolide (COST) against oxidative tissue damage in the ovarian torsion/detorsion (TD) model. Methodology Animals were randomly assigned to sham, ovarian TD, COST 5 mg/kg + ovarian TD, and COST 10 mg/kg + ovarian TD groups. COST’s effectiveness was determined by assessing oxidative stress markers, interleukin levels, and histopathological examinations. Results Oxidative stress markers were elevated in the ovarian TD group compared to the sham group. COST treatment represented a decline compared to the TD group. Besides, the antioxidant activity was significantly higher in the ovarian TD group than in the sham group. COST treatment improved the antioxidant parameters compared to the TD group. Inflammatory parameters, such as tumour necrosis factor- alpha (TNF-α) and interleukin 1-beta (IL-1β) were higher in the ovarian TD group than the sham group. Conclusion COST treatment suppressed the proinflammatory cytokine expression compared to the TD group. Histopathological data supported these findings.

Sequential Administration of Febuxostat, Amlodipine and Vitamin E Attenuate Oxidative Stress and Improve Spermatogenesis in Testicular Ischemia Reperfusion Injury in Wistar Rats

This study investigated the effects of sequential administration of febuxostat, amlodipine, and vitamin E on oxidative stress and spermatogenesis following testicular ischemia-reperfusion injury (TIRI) in Wistar rats. Ninety male rats (120-150 g) were divided into 9 groups (n=10 each): sham operation (SO), torsion-detorsion (TD), and seven treatment groups receiving different combinations of the drugs. The treatment groups included torsion + febuxostat + detorsion (TFD), torsion + detorsion + amlodipine (TDA), torsion + detorsion + vitamin E (TDV), and combinations thereof (TFDA, TFDV, TDAV, TFDAV). TIRI was induced by 720° clockwise testicular torsion for 1 hour followed by detorsion. Febuxostat (5 mg/kg) was administered 30 minutes after torsion, amlodipine (2.5 mg/kg) immediately upon detorsion, and vitamin E (10 mg/kg) 30 minutes after detorsion. Rats were sacrificed 56 days post-reperfusion. Testicular tissue was analyzed for antioxidant enzymes (superoxide dismutase, catalase), lipid peroxidation (malondialdehyde), total protein, inflammatory markers (serum nitrite, IL-1β), and spermatogenesis indices (testicular biopsy score, Leydig cell count). Results showed that TIRI significantly decreased antioxidant enzymes, significantly increased lipid peroxidation and inflammatory markers, and impaired spermatogenesis. In the TD group, superoxide dismutase (SOD) and catalase (CAT) activities were significantly decreased, while malondialdehyde (MDA) increased significantly compared to the SO group (p<0.01). Serum nitrite and IL-1β levels in the TD group were also increased (p<0.001). Furthermore, the testicular biopsy score and Leydig cell count in the TD group were significantly decreased in this study (p<0.01). Sequential administration of febuxostat, amlodipine and vitamin E, particularly when all three were used (TFDAV group), significantly attenuated these changes. In the TFDAV group, SOD and CAT activities were improved, while MDA decreased compared to the TD group (p<0.05). Serum nitrite and IL-1β levels in the TFDAV group were also decreased (p<0.001). In addition, the testicular biopsy score and Leydig cell count in the TFDAV group increased in comparison with the TD group (p<0.001). The study concludes that this sequential multi-drug approach shows promise in mitigating the long-term detrimental effects of TIRI on testicular function and fertility. The combination of febuxostat (a xanthine oxidase inhibitor), amlodipine (a calcium channel blocker), and vitamin E (an antioxidant) appears to provide protection against oxidative stress and inflammation induced by TIRI, thereby preserving spermatogenesis.

Effect of Cinnamon Extract on Ovarian Torsion Detorsion Damage in Rats

Effect of Cinnamon Extract on Ovarian Torsion Detorsion Damage in Rats

The Effect of Rosmarinic Acid Against Ovarian and Lung Injuries Induced by Ovarian Torsion Detorsion in Rats

Background: Here, we purposed to find out the effects of two different Rosmarinic acid (RA) doses against lung injury caused by ovarian ischemia-reperfusion. Materials and Methods: We planned the groups as sham, ovarian torsion detorsion (O/TD; 3hours torsion/3hours detorsion), RA 40 mg/kg (40 mg/kg RA+O/TD), and RA 80 mg/kg (80 mg/kg RA+O/TD) groups. Following the experimental procedure, we sacrificed the rats and then, collected the lung and ovarian tissues for biochemical evaluations. Result: Total oxidant status (TOS), myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and oxidative stress index (OSI) were elevated in the O/TD group compared to the sham group. These parameters declined due to low and high doses of RA administration. Total antioxidant status (TAS) level and superoxide dismutase (SOD) activity diminished in the O/TD group while increasing in RA treatment groups. However, the high dose of RA treatment group enhanced the antioxidant activity further and reduced the oxidant parameters compared to the low dose RA treatment group. Conclusion: In this study, RA treatment reduced O/TD-induced ovarian and lung injuries in the experimental animals.

Exosomes obtained from adipose mesenchymal stem cells prevent ischemia-reperfusion injury after torsion-detorsion in rat testes.

To investigate the effect of exosomes obtainedfrom adipose-derived mesenchymal stem cells (AD-MSCs) on testicular ischemia-reperfusion (I/R) injury. AD-MSCs from rat adipose tissue were cultured. Characterization of cells was evaluated with CD44, CD90, CD34 and CD45 antibodies. Exosomes from AD-MSCs were obtained with the miRCURYexosomeisolation kit. 21 rats were divided into 3 groups. The I/R model was created as 720° torsion for 4h and reperfusion for 4h. In the Sham group (SG), only scrotal incision was made. 100µl of medium in the torsion-control group (T-CG) and 100µl of exosome in the treatment group (TG) were injected into the testicular parenchyma after detorsion. Johnsen scores of testicles were determined. Apoptosis was evaluated by the TUNEL method. It was observed that the seminiferous tubule structures were partially disrupted in T-CG, but normal in SG and TG. Johnsen scores in SG, T-CG, and TG were 8.64 ± 0.39, 7.71 ± 0.37, and 8.57 ± 0.39, respectively. Apoptotic cell distribution was 11.28 ± 5.25%, 60.58% ± 1.68% and 17.71 ± 8.34% in SG, T-CG and TG, respectively. In both parameters, the difference between SG and TG was insignificant (p > 0.05), the difference between T-CG/TG and SG/T-CG was significant (p < 0.05). Exosomes obtainedfromAD-MSCs are effective in preventing testicular I/R injury. This effect appears to occur because of suppression of apoptotic activity.

The Flavonoid Chrysin Protects against Testicular Apoptosis Induced by Torsion/Detorsion in Adult Rats

In the present work, we examined the beneficial efficacy of chrysin as a natural flavonoid on testicular torsion/detorsion damages among adult male rats. Forty-eight male Wistar rats were randomly allocated into six groups: sham, torsion/detorsion (TD) group, TDC30 group in which TD process was applied and treated with chrysin (30 mg/kg), TDC50 group in which TD process was applied and treated with chrysin (50 mg/kg), HC30 group in which animals were treated with chrysin (30 mg/kg), and HC50 group in which rats were treated with chrysin (50 mg/kg). Serum samples were tested for testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. The sperm parameters, histopathological analysis, and expressions of apoptosis-related genes were examined among different groups. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels in the testicles and serum were measured. Serum levels of SOD, GPx, FSH, LH, and “Bax” expression significantly increased in the TD group compared to the sham group ( P &lt; 0.05 ). Sperm parameters, serum testosterone level, Johnson’s scores, seminiferous tubule diameter, the height of the germinal epithelium (HE) measurements, and expression of “Bcl2” meaningfully decreased ( P &lt; 0.05 ). Administration of chrysin impeded ischemia/reperfusion damages in testis tissue and improved sperm quality. The result of our study indicates that treatment with chrysin can protect testis tissue from ischemia/reperfusion damages induced by TD procedure.

Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion-detorsion.

Testicular torsion-detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage. To determine the effect of pentoxifylline on germ cell survival in torsion-detorsion induced apoptosis Methods: Twenty male mice were divided into four groups of five animals each: Control, T1 (Torsion-detorsion+single dose 100mg/kg Pentoxifylline/IP), T2 (Torsion-detorsion+daily 20mg/kg pentoxifylline/IP for 2weeks, and T/D (Torsion-detorsion only). 35thday after torsion-detorsion, the left testes of all the animals were harvested for histological and biochemical analysis. Histomorpholoical analysis showed significant increase (P <0.05) in seminiferous tubule diameter, Johnsen's score and germ cells of Control and T1 compared to T2 and T/D, with no significant difference (P >0.05) in testis weight, sertoli, leydig and myoid cells. Tunnel assay showed significant increase (P <0.05) in apoptotic cells of T/D and T2 animals compared to Control and T1. RT-PCR analysis showed significant high (P <0.01) mRNA expression of Bax gene in T/D compared to T1 and T2 and significant increase (P <0.05) of Bcl2 in Control, T1, T2 compared to T/D. Nrf2-ARE transcripts revealed significant increase (P <0.05) in Control and T1 compared to T2 and T/D. Western blot showed significantly increased (P <0.05) caspase-3 in T/D compared to Control, T1 and T2. Pentoxifylline promotes spermatogenesis and suppressed apoptosis induced by testicular torsion-detorsion. Pentoxifylline could serve as adjunct therapy to surgery in the treatment of torsion-detorsion induced germ cell apoptosis.

Protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse spermatogenesis and sperm chromatin condensation following unilateral testicular torsion

Testicular torsion is considered a urological disorder that requires immediate detorsion surgery. Ischemia/reperfusion (I/R) injury after testicular torsion detorsion causes of drastic impairment of spermatogenesis and infertility. Cell-free-based approaches seem to be a promising strategy to prevent I/R injury, they have more stable biological properties, and they contain paracrine factors of mesenchymal stem cells. The purpose of this study was to evaluate the protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse sperm chromatin condensation and spermatogenesis improvement after I/R injury. hAMSCs were isolated and characterized by RT- PCR and flow cytometry, preparation of hAMSCs secreted factors was performed. Forty male mice were randomly divided into 4 groups: sham-operated, torsion detorsion, torsion detorsion+ intratesticular injection of DMEM/F-12, and torsion detorsion+ intratesticular injection of hAMSCs secreted factors. After one cycle of spermatogenesis, the mean number of germ cells, Sertoli, Leydig, myoid as well as tubular parameters, Johnson score, and spermatogenesis indexes were evaluated by H& E and PAS stainings. Sperm chromatin condensation and relative expression of c-kit and prm 1 genes were assessed by aniline blue staining and real-time PCR, respectively. The mean number of spermatogenic cells, Leydig, myoid, Sertoli, spermatogenesis parameters, Johnson score, as well as germinal epithelial height and diameters of seminiferous tubules decreased significantly after I/R injury. The thickness of basement membrane and percentage of sperm with excessive histone significantly increased, while the relative expression of c-kit and prm 1 significantly decreased in torsion detorsion group (p 0.001). hAMSCs secreted factors remarkably restored normal sperm chromatin condensation, spermatogenesis parameters and histomorphometric organization of seminiferous tubules via intratesticular injection (p 0.001). Thus, hAMSCs secreted factors may potentially salvage torsion-detorsion-induced infertility.

Oct4 reduction contributes to testicular injury of unilateral testicular torsion in mice model and apoptotic death of Sertoli cells through mediating CIP2A expression

This study explored the mechanism of ipsilateral testis injury after ipsilateral testicular torsion detorsion (T/D) and the potential testis-protective part of the octamer-binding transcription factor 4 (Oct4)-cancerous inhibitors of protein phosphatase 2A (CIP2A) axis in a T/D animal model and in ischemia–reperfusion (IR)-treated testicular Sertoli TM4 cells. Quantitative Polymerase chain reaction (PCR) and western blot (WB) confirmed the downregulation of both CIP2A and Oct4 expression in the testicular tissue from T/D mice compared with sham-operated mice. T/D model was then established in mice with upregulated Oct4 expression in the testis. Oct4 elevation restored CIP2A expression in testes after T/D treatment. Furthermore, we observed that an increase in Oct4 ameliorated the testicular damage caused by torsion in the testis. Biochemical analysis indicated that T/D treatment increased serum anti-sperm antibody levels, but reduced testosterone levels. Meanwhile, in testicular tissue, reactive oxygen species (ROS), malondialdehyde (MDA), and activity of testicular myeloperoxidase (MPO) enzymes were promoted, while glutathione peroxidase activity (GPx) was decreased by T/D injury. Notably, testicular Oct4 restoration partially counteracted the effect of T/D treatment on these biochemical indices. Hypoxia/reoxygenation (HR) treatment was applied to TM4 cells to mimic TT injury in vitro. A gain-of-function study showed that Oct4 overexpression partly counteracted the promoting role of HR in cell damage, apoptosis, and oxidative stress in TM4 cells. These observations provide novel insights into the possible biochemical mechanism underlying the mediation of the Oct4-CIP2A axis in T/D injury.

The Role of p-Coumaric Acid on Reproductive and Remote Organ Damages Created by Adnexal Torsion/Detorsion: Biochemical and Immunohistochemical A Study

Objective: We planned to search the effects of p-coumaric acid on ovary and lung injuries formed via bilateral adnexal torsion detorsion (T/D) in experimental rat model. Methods: 24 female, Sprague-Dawley rats were sorted out as 3 groups. Design of the groups was performed as sham (group I) and T/D (group II), p-coumaric acid+T/D (group III) groups. Sham group; abdomen area was applied incision and repaired with no T/D model application. T/D group; 3 h of torsion phase completed and then 3 h of detorsion stage was established. P-coumaric acid+T/D group; p-coumaric acid was administered at the dose of 100 mg/kg for 15 days by oral gavage and then, T/D model was performed. Following detorsion phase, rats were sacrificed, lung and ovarian tissues were excised for biochemical and immunohistochemical evaluations. Results: When it is compared to group I, oxidant parameters elevated significantly in group II (p&amp;lt;0.05) while the activity of antioxidant enzymes and TAS level decreased. On the other side, antioxidant enzyme activity raised and oxidant parameter levels diminished in group III compared to group II (p&amp;lt;0.05). Moreover, NF-kB, caspase 3 and LC3B protein expression levels increased in ovary and lung tissues of the group II. But NF-kB, caspase 3 and LC3B protein expression levels decreased in group III. Conclusion: As a consequence, p-coumaric acid acted a protective performance against ovary and lung injuries arising from adnexal T/D model in rats.

Letter to the Editor in reference to the article entitled 'Intraoperative evaluation of testicular vascularization and perfusion in rat testicles with indocyanine green (ICG)/near-infrared (NIR) fluorescent imaging after torsion-detorsion and reperfusion'.

Letter to the Editor in reference to the article entitled 'Intraoperative evaluation of testicular vascularization and perfusion in rat testicles with indocyanine green (ICG)/near-infrared (NIR) fluorescent imaging after torsion-detorsion and reperfusion'.

Intraoperative evaluation of testicular vascularization and perfusion in rat testicles with indocyanine green (ICG)/near-infrared (NIR) fluorescent imaging after torsion-detorsion and reperfusion.

The aim of this study was to evaluate testicular perfusion and vascularization with intraoperative ICG/NIR imaging in a testicular ischemia-reperfusion model and to investigate the effects of ICG on testicular tissue. 24 male rats were divided into four groups. In the ICG group, only ICG was given and images of the testicles were recorded with NIR camera. In the torsion group, the testicles were left in torsion for 4h. ICG/NIR images were obtained after torsion and detorsion. In the reperfusion group, ICG/NIR images of the testicles were obtained at the 4th hour of reperfusion. After the procedures, testicles were collected and evaluated with histological, immunohistochemical examination and qRT-PCR. There was no histologically negative effect of ICG on testicular tissue. There was no testicular perfusion in the torsion group, but perfusion started after detorsion. At the 4th hour of reperfusion, testicular perfusion continued. TNF-a, IL-6, MCP-1 and caspase-3 immunoreactivity were found to be at low levels in the control and ICG groups, while high in the torsion and reperfusion groups (p < 0.05). In qRT-PCR, TNF-a, IL-6, MCP-1 and caspase-3 expressions were lower in the control and ICG groups, but higher in the torsion and reperfusion groups. There was no histologically negative effect of ICG on testicles. The ICG/NIR imaging technique seems to be a feasible method in testicular torsion and may contribute to the surgeon in the intraoperative management of testicular torsion. In testicles that started to be perfused after detorsion, perfusion still continued at the 4th hour of reperfusion. Our next goal is to test whether testicles showing ICG fluorescence in during reperfusion maintain their viability for long term.

Impact of Enoxaparin +α Lipoic acid combination on oxidative stress, follicle development and apoptotic damage in ovarian ischemia reperfusion model.

With this study we aimed at investigating the impact of enoxaparin (E) and α-lipoic acid (α-LA) on ischemia/reperfusion (I/R) damage in an experimental ovarian torsion (T) detorsion (D) model. The study comprised 80 female albino rats aged 12 weeks. They were divided into 8 groups as follows, with 10 rats in each group: Group 1 (Sham), Group 2 (Ischemia, 3 hours), Group 3 (I/R, 6 hours reperfusion), Group 4 (I/R, 3 days reperfusion), Group 5 (I/R, E, 6 hours), Group 6 (I/R, E, 3 days), Group 7 (I/R, E+α-LA, 6 hours), and Group 8 (I/R, E+α-LA, 3 days). Immediately after detorsion, enoxaparin (0.5 mg/kg/day, sc) or α-LA (100 mg/kg/day, ip) were administered. Ovarian levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and catalase were measured. In addition to total Antioxidant Status (TAS) and Total Oxidative Stress (TOS), the Oxidative Stress Index (OSI) was calculated. Serum levels of AMH, FSH, LH, E2, and progesterone were measured. Ovarian samples were histopathologically examined and they underwent Tag staining for apoptosis. Compared with the sham group, there was a significant increase in TOS, OSI, and MDA levels in I/R group (p<0.001). Compared to Group 2, a significant increase was determined in TOS and OSI in Group 3 (p<0.05). In Group 4, a significant increase was found compared to Group 2 (p<0.01). The lowest level of I/R damage and the highest level of antioxidants were found in Group 2, 7, and 8. The highest values of TOS, OSI, and MDA were found in Group 3, Group 4, Group 5, and Group 6 (p<0.001). When the sham group and Group 4 were compared, it was found that AMH and E2 levels decreased (p<0.001), while FSH levels increased (p<0.001). In Group 6, AMH and E2 values were significantly decreased compared to the sham group (p<0.001). In the histopathological examination, the findings were observed to be parallel to those of the biochemical markers. Combined use of α-Lipoic acid and enoxaparin prevents oxidative stress and ovarian damage due to ischemia-reperfusion injury better than the use of drugs alone.

Evaluating the effects of betaine on testicular ischemia/reperfusion injury induced by torsion/detorsion in the rat.

In this research, the effects of betaine on testicular ischemia-reperfusion were evaluated. Forty rats were randomly divided into 4 groups of sham, torsion/detorsion (TD), torsion/detorsion with two different dosage of betaine 200 mg/kg, and 300 mg/kg, respectively. At the end of the experiment, the testosterone concentration, sperm motility, concentration and vitality, oxidative stress biomarkers including Malondialdehyde (MDA), Glutathione peroxidase (GPx), Catalase (CAT), and total antioxidant capacity (TAC) were assessed. Moreover, histopathological parameters including seminiferous tubules diameter (STD), seminiferous epithelium thickness (SET), spermatogonia nuclei diameter (SpND), Sertoli cell nuclei diameter (StND) and miotic index were evaluated. The testosterone concentration altered during torsion/detorsion and betaine could increase slightly the testosterone concentration after 15 days. Sperm motility and vitality significantly increased in the betaine treated groups compared to the TD group on days 3 and 15. Among oxidative stress biomarkers, only CAT on day 3 and GPx on day 15 were significantly higher in the betaine groups compared to the TD group. Among histopathological parameters an increase in the STD and SET in betaine-200 and betaine-300 groups were observed on 15th day of post-surgery, compared to the TD group. These findings indicate that betaine can ameliorate testicular damages triggered by torsion/detorsion.

Autophagy comparative after decompression of tunica albuginea in testicular torsion in mature and immature rat

BackgroundOne of the types of catabolic processes in cells is autophagy, which maintains cell homeostasis. It is also known as a defense response to oxidative stress. This study aimed to track the autophagic activity of testicular tissue in mature and immature rats in 3 conditions: (1) physiologic, (2) under increased pressure in the tunica albuginea compartment following the induction of testicular torsion, and (3) decompression of this compartment by flap technique. MethodsThis study was performed on 72 Wistar rats divided into 3 mature and 3 immature groups, each of the groups including Sham group, testicular torsion induction group for 6 hours (Torsion Detorsion), and testicular torsion induction group for 6 hours, followed by the flap technique. ResultsIn the physiologic state or Sham, autophagic indices (LC3, Beclin-1) are active, and more activity was observed in mature rats, compared with immature ones, which indicated the activity of this process during development and maturity. In the Torsion Detorsion group, significant expression of autophagy and apoptosis indices (caspase3) was observed along with the degradation of spermatogenesis and steroidogenesis. It seems that in this state, the activation of autophagy leads to programmed death and is in line with apoptosis. Finally, in the flap technique group, an increase in the expression of autophagy indices was accompanied by a reduction in the expression of apoptotic indices and improved spermatogenesis and steroidogenesis. ConclusionDecompression of tunica albuginea by flap technique can activate of autophagy process to save tissue function and eliminate stress caused by testicular torsion.

Evidence that the myocardium is a continuous helical muscle with one insertion

Introduction and objectivesAnatomically, the heart cannot be suspended in the thorax without structural continuity of the heart muscle to pump blood at a speed of 200cm/s with an efficacy that allows ejecting 70% of the left ventricular volume with only 12% shortening of its contractile unit, the sarcomere. The aim of this study was to investigate a) whether the myocardium is a single, continuous, helical muscle; b) the origin and end of the myocardial muscle; and c) the sliding movement between the myocardial segments during ventricular torsion–detorsion. This forces us to think of an antifriction mechanism. MethodsA total of 18 hearts (10 bovine and 8 human) were used for anatomical and histological studies. Histological an histochemical analysis of the samples were performed, using the Alcian Blue technique to confirm hyaluronic acid and its antifriction mechanism. ResultsThe myocardium could be defined as a single, continuous, and helical muscle that is inserted at its origin and end, according to the specimens analyzed, to an osseus-chondroid-tendinous nucleus called cardiac fulcrum, thus limiting the 2 ventricular chambers. Hyaluronic acid was found in the excision planes between the myocardial bundles. ConclusionsThe myocardium in its longitudinal continuity adopts a spiraling spatial configuration, inserted at its end to a nucleus called cardiac fulcrum. The Thebesian veins and hyaluronic acid could have an essential role in the antifriction mechanism, due to the resistance between the sliding myocardial muscle surfaces in their torsion (systole) and detorsion (suction) motions.

Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.

Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation.

Objective(s):This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. Materials and Methods:40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1β, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed.Results:In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1β, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage.Conclusion:These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.

Effect of sunitinib on testicular oxidative and proinflammatory damage induced by ischemia–reperfusion in rats

IntroductionThis study aimed to biochemically and histopathologically investigate the effect of sunitinib on oxidative testicular damage induced by ischemia/reperfusion in rats. Material-methodExperimental animals were divided into three groups of six rats each: testicular torsion–detorsion (TTD), sunitinib+testicular torsion–detorsion (STD), and sham control (SC). Sunitinib (25mg/kg) was administered orally to the STD group by gavage. Normal saline (0.9% NaCl) was administered orally to the TTD and control groups as the solvent. One hour after administration of sunitinib and 0.9% NaCl, all animal groups were done torsion–detorsion. Then, all the rats were killed by high-dose anesthesia, and their testicles were removed. Biochemical and histopathological examinations were performed on the removed testicular tissues. ResultsMalondialdehyde; it was observed that the results in the STD group were close to those of the SC group and statistically significant lower compared to the TTD group (p=0.001). The glutathione values were statistically significantly higher in the STD group compared to the TTD group (p<0.001). Nuclear factor kappa B values, revealing a statistically significant difference between the TTD and STD groups (p<0.001). The TNF-α levels were measured and indicating that the results of the STD group were statistically significantly lower than those of the TTD group (p<0.001). Histopathologically, animal tissues given sunitinib were observed to resemble normal tissues. ConclusionSunitinib was shown to prevent histopathological changes in testicular tissue against ischemia/reperfusion damage.

Effects of hypothermia and pentoxifylline on the adnexal torsion/detorsion injuries in a rat testis model.

This study was designed to investigate the effects of separate and combined administration of hypothermia and pentoxifylline to preserve the effects on the testicles in an experimental model of testicular torsion/ detorsion injuries in rats. Forty male adult Wistar rats were randomly divided into five groups, control, torsion/detorsion (TD), torsion/detorsion/hypothermia (TD+ICE), torsion/detorsion received of pentoxifylline (40mg/kg, ip) (TD+PTX) and torsion/detorsion/hypothermia/PTX (TD+ICE+PTX). Left testicular torsion (TT) was performed for 4 and half hours, and ice fragments have been used at the beginning of torsion. After the reperfusion period (a week), oxidative maker's serum levels, testosterone hormone, sperm parameters, and histopathological and gene expression evaluations have been performed. Significant adverse changes were observed in the TD group for histological variables, sperm count, oxidative marker, testosterone hormone, Bax, BCL2 and caspase-3 expression. The parameters studied in the group receiving PTX improved in comparison with the TD group, while macroscopical parameters of both the hypothermia and PTX+ICE groups were not different compared with the TD group. The results revealed that PTX, as an antioxidant component, was protective against testicular torsion, while hypothermia and hypothermia plus PTX did not exhibit this property, which may have been due to the duration of hypothermia (4hr) or reperfusion period.