The potential prophylactic and therapeutic impacts of niacin on ischemia/reperfusion injury of testis.

INTRODUCTION: The testicular ischemia-reperfusion (I/R) injury is characterized by the excessive aggregation of un-scavenged reactive oxygen species, leading to the heightened levels of oxidative stress. This phenomenon plays a pivotal role in the pathophysiology of testicular torsion damage. OBJECTIVE: The current study aimed to detect the prophylactic and therapeutic effects of niacin on testicular I/R injury. STUDY DESIGN: Twenty-four healthy adult male Sprague Dawley rats were randomly allocated into three groups as follows: (1) sham group, (2) torsion/detorsion (T/D) group, and (3) treatment group which received 200 mg/kg niacin along with testicular T/D. Torsion/detorsion was induced by 2 h of torsion followed by 10 days of reperfusion period. In the treatment group, niacin was injected 30 min before the reperfusion period intraperitoneally and continued for 10 days by oral gavage. RESULTS: T/D was associated with marked decreases in terms of sperm count, viability, and kinematic parameters versus the sham group (P < 0.05), which niacin significantly reverted the kinematic parameters (P < 0.05). I/R injury caused a significant increase in the number of abnormal epididymal sperms compared to the sham group (P < 0.05). Niacin decreased the epididymal sperm abnormality significantly compared to the T/D group (P < 0.05). Tissue abnormalities in T/D group, such as edema, hyperemia, inflammation, and necrosis were completely visible histopathologically, while the histological changes in the niacin-treated group were better than those in the T/D group. Regarding the pathological parametric evaluations, I/R injury significantly reduced the mean testicular biopsy score (MTBS), germinal epithelial cell thickness (GECT), and mean seminiferous tubular diameter (MSTD), and increased the tubular hypoplasia/atrophy (THA) compared to the sham group (P < 0.05), which niacin treatment significantly improved the MTBS and GECT compared to the T/D group (P < 0.05). T/D significantly increased the oxidative stress index (OSI) and lipid peroxidation (MDA) (P < 0.05). Niacin significantly reduced the OSI and MDA levels compared to the T/D group (P < 0.05). DISCUSSION: The current study found that niacin has preventive/therapeutic effects against the elevation of oxidative stress markers and depletion of antioxidants during I/R injury. Following administration of niacin, a reduction in histologic injury was observed in rats. In our study, we showed the antioxidant properties of niacin and its capacity to protect against I/R damage. CONCLUSION: The findings of the present investigation revealed that niacin, as an antioxidant agent, can suppress the oxidative stress induced by testicular I/R injury, and can be used as a supplementary agent in the treatment of those undergoing testicular torsion surgery.

MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL CHANGES IN THE GONADS OF CHILDREN 2-6 HOURS AFTER ACUTE UNILATERAL TESTICULAR TORSION.

OBJECTIVE: The aim: To determine the morphological and immunohistochemical changes in the testes 2-6 hours after the onset of clinical symptoms of acute unilateral testicular torsion. PATIENTS AND METHODS: Materials and methods: A morphological and immunohistochemical study was conducted on biopsy samples of testicular tissues taken 2-6 hours after the onset of clinical symptoms of acute unilateral testicular torsion during detorsion and orchiopexy surgery in 27 adolescent patients. RESULTS: Results: In cases of incomplete torsion (180-360°) and a disease duration of up to 2 hours, the seminiferous tubules maintained their normal structure. The convoluted seminiferous tubules showed minor damage during 4 hours of ischemia caused by testicular torsion of 360-450°, which was characterized by mild damage. Glycogen and neutral glycoproteins were preserved in the cytoplasm of spermatogonia, primary spermatocytes, and Sertoli cells, indicating that their intracellular metabolism was relatively preserved. The ischemia that lasted for 4 hours with testicular torsion of 450-720° was characterized by a moderate degree of gonadal damage. However, there was pronounced expression of vimentin and calretinin, and the presence of glycogen and neutral glycoproteins indicated functional activity of the gonads. A six-hour ischemia period with a 360-450° testicular torsion demonstrated 100% gonadal viability, with 50% of the seminiferous tubules preserved and 35% with minor damage. Severe damage to the spermatogenic epithelium was observed in 15% of seminiferous tubules, characterized by dystrophy of spermatogenic epithelial cells with signs of karyopyknosis, karyorrhexis, vacuolization, hyperchromasia of cytoplasmic organelles, shedding of individual cells into the lumen of tubules, and focal necrosis. CONCLUSION: Conclusions: 1. The degree of torsion and duration of symptoms are prognostic factors for testicular salvage in torsion episodes. Ischemia lasting up to 6 hours is characterized by a moderate degree of gonadal damage, and detorsion of the testicle performed within 6 hours from the onset of pathology allows for preservation of the testicle in 100% of cases. 2. Histological examination of the susceptibility of different cell types to ischemia reveals that Sertoli cells and spermatogonia are the most resistant, while spermatocytes and spermatids are more susceptible and prone to degeneration.

Protective effects of Silymarin on testicular torsion/detorsion in rats.

OBJECTIVE: The present research aimed to study the possible protective effects of Silymarin on testicular I/R injury in a rat model evaluated through histopathology and biochemical parameters. MATERIALS AND METHODS: This research investigated the impact of Silymarin on IR damage in male Wistar albino rats. Animals were divided into three groups: group 1 (sham), group 2 (IR), and group 3 (IR+Silymarin). RESULTS: There were no notable differences in the levels of malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) across the three groups (p=0.260, p=0.486 and p=0.803, respectively). Contrarily, the total antioxidant status (TAS) levels exhibited significant variations between groups (p=0.001). The total oxidant status (TOS) levels also differed significantly between groups (p=0.004). The tissue evaluations uncovered substantial differences in the Johnson score, which is used to gauge testicular damage. A distinct contrast was seen between Group 1 and Group 2, and also between Group 2 and Group 3, with an all-encompassing p-value lower than 0.01. The same significant disparities were found for the percentages of Bax and Annexin V immunostaining (p<0.01 for each), reflecting the inflammation and apoptosis brought about by ischemia-reperfusion and the protective effects of the treatment. CONCLUSIONS: The outcomes of the current investigation showed that Silymarin could be a valuable agent for reducing testicular tissue damage following I/R injury.

Pretreatment with remote ischemic conditioning attenuates testicular damage after testicular ischemia and reperfusion injury in rats.

Testicular torsion is a urological emergency. However, surgical detorsion of the torsed spermatic cord can cause testicular reperfusion injury. Although remote ischemic preconditioning (RIPC) has been convincingly shown to protect organs against ischemia/reperfusion (I/R) injury, little is known regarding the effect of RIPC on testicular torsion/detorsion-induced reperfusion injury. Therefore, we aimed to evaluate the effect of RIPC on testes after testicular I/R injury in a rat model in vivo. Male Sprague-Dawley rats were randomly classified into 4 groups: sham-operated (sham), testicular I/R (TI/R), or remote liver (RIPC liver) and limb (RIPC limb) ischemic preconditioning groups. Testis I/R was induced by 3 h of right spermatic cord torsion (720° clockwise), and reperfusion was allowed for 3 hours. In the RIPC group, four cycles of 5 min of ischemia and 5 min of reperfusion were completed 30 min prior to testicular torsion. The ERK1/2 inhibitor U0126 was administered intravenously at the beginning of reperfusion (1 mg/kg). The testes were taken for the oxidative stress evaluations, histology, apoptosis, immunohistochemical and western blotting analysis. Remote liver and limb ischemic preconditioning attenuated ipsilateral and contralateral testicular damage after testicular I/R injury. For example. RIPC reduced testicular swelling and oxidative stress, lessened structural damage, and inhibited the testicular inflammatory response and apoptosis. Furthermore, RIPC treatment enhanced testicular ERK1/2 phosphorylation postI/R. Inhibition of ERK1/2 activity using U0126 eliminated the protection offered by RIPC. Our data demonstrate for the first time that RIPC protects testes against testicular I/R injury via activation of the ERK1/2 signaling pathway.

Infarction of Paratesticular Inflammatory Myofibroblastic Tumor Mimicking Testicular Torsion.

This report describes a 14-year-old male with a rare paratesticular inflammatory myofibroblastic tumor that presented atypically with acute unilateral scrotal pain and swelling. This presentation, which raised suspicion for testicular torsion, contrasts with the typical presentation of a slow-growing scrotal mass. Scrotal exploration revealed an infarcted right testis, demonstrating this locally aggressive tumor can undergo vascular invasion and occlude testicular blood supply. Thus, inflammatory myofibroblastic tumor should be considered in the differential diagnosis when evaluating patients with acute scrotal pain suspicious for testicular infarction.

Arbutin abrogates testicular ischemia/reperfusion injury in rats through repression of inflammation and ER stress.

The aim of this study was to investigate the effects of arbutin (ARB) administration on oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis in an experimental testicular torsion/detorsion (T/D)-induced testicular injury model for the first time. A total of 24 male Sprague-Dawley rats were divided into four groups with six rats in each group: sham control, T/D, T/D+ARB (50 mg/kg) and T/D+ARB (100 mg/kg). Torsion and detorsion times were applied as 4 h and 2 h, respectively. The levels of lipid peroxidation [malondialdehyde (MDA)] and oxidative stress [total oxidant status (TOS) and total antioxidant status (TAS)] in testicular tissues were determined using colorimetric methods. The levels of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], antioxidant system [superoxide dismutase (SOD) and catalase (CAT)], pro-inflammatory cytokines [high mobility group box 1 (HMGB1), nuclear factor kappa B protein 65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO)], ER stress [78-kDa glucose-regulated protein (GRP78), activating transcription factor 6 (ATF6) and CCAAT-enhancer-binding protein homologous protein (CHOP)] and apoptosis (caspase-3) markers in testicular tissues were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In the T/D group, it was determined that statistically significant increasing in the levels of oxidative stress, inflammation, ER stress and apoptosis compared with sham control group (p < 0.05). ARB administrations statistically significantly restored testicular I/R damage in a dose dependent manner (p < 0.05). In addition, it was determined that the data of histological examinations supported the biochemical results. Our findings support the hypothesis that ARB may be used as a protective agent against T/D-induced testicular damage.

Effect of ferulic acid on testicular damage caused by torsion-detorsion in rats.

Testicular torsion is twisting of the spermatic cord around its axis, which impairs blood flow and causes ischemia and formation of free radicals. Ferulic acid is a phenolic acid of the hydroxycinnamic family that is found in the seeds and leaves of plants; it is present in substantial amounts in fruits and vegetables. We investigated the protective effect of ferulic acid on experimental testicular torsion in rats. Animals were divided randomly into five groups: control, ethyl alcohol, torsion, torsion-detorsion, and torsion-detorsion + ferulic acid. Histopathology was assessed using hematoxylin and eosin, and periodic acid-Schiff staining. Tissues were assessed using TUNEL, active caspase-3, myeloperoxidase and inducible nitric oxide synthase immunostaining. Biochemical changes were assessed using assays for superoxide dismutase, malondialdehyde, glutathione peroxidase and glutathione. Ferulic acid reduced the levels of free radicals and increased the levels of antioxidants. Ferulic acid also reduced histopathological changes and germ cell differentiation in the testis following torsion-detorsion. Ferulic acid should be investigated further as a potential treatment for sequelae of torsion-detorsion injury.

Testicular and scrotal abnormalities in pediatric and adult patients.

Testicular and scrotal abnormalities can occur in children, adolescents, and adults. The lesions, often accompanied by pain and swelling/enlargement of the scrotum, can cause anxiety in patients and their parents. Regardless of age, proper diagnosis is based on adequate anamnesis and physical examination. Color Doppler ultrasound is the first-line test in the differential process of testicular and scrotal diseases. Testicular and scrotal lesions require differentiation for benign and malignant processes as well as therapeutic management, including urgent surgical intervention. The aim of this paper is to present the most common causes of testicular and scrotal abnormalities in pediatric and adult patients and to outline the symptoms and diagnostic and therapeutic management.

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.

The impact of bone marrow-derived mesenchymal stem cells on experimental testiculartorsion in rats.

BACKGROUND: The aim of this study was to investigate the healing effects of bone marrow-derived mesenchymal stem cells (BMMSCs) on experimental testicular torsion in rats. METHODS: Three groups consisting of 10 Wistar albino rats were created. In Group I, the left testicle was explored and relocated in the scrotum without any attempt to modify it. In Group II, the left testicle underwent torsion for three h and then was detorsed and relocated. In Group III, in addition to torsion and detorsion, BM-MSCs were administered intratesticularly. The rats were sacrificed on the seventh day, and the healing status of the testicles was investigated with histopathological and biochemical analyses. BM-MSC involvement was investigated by immunofluorescence microscopy. Statistical analysis was performed using SPSS 15.0. A p-value < 0.05 was considered statistically significant for all variables. RESULTS: Immunofluorescence microscopy showed that BM-MSCs were located around the Leydig cells in Group III. Under light microscopy, the mean Johnsen Score of Group III was significantly higher than that of Group II (p = 0.035). The interleukin-10 (IL-10) level was significantly higher in Group III compared to Group II (p = 0.003). While the malondialdehyde (MDA) values in Group I (the control group) were lower than in the other groups (p = 0.037), the superoxide dismutase (SOD) values were similar (p = 0.158). Although there was no statistically significant difference between Group II and Group III in terms of MDA, it was lower in Group III. Although the tissue SOD levels were higher in Group III than in Group II, the difference was not statistically significant. DISCUSSION: : This study has demonstrated that BM-MSCs significantly corrected the Johnsen Score and increased anti-inflammatory cytokine levels after testicular torsion. BM-MSCs can be used in testicular torsion as supportive therapy to minimize tissue damage.

Shear wave elastography for the evaluation of testicular salvage after testicular torsion.

The aim of this study was to assess the utility of shear wave elastography in the follow-up of testicular detorsion, evaluate long-term outcomes, and explore its relationship with parameters such as tissue stiffness values, pain duration, and torsion type. Elastography examinations were independently performed by two radiologists to evaluate patients who presented to our hospital for follow-up after being diagnosed with testicular torsion and age-matched controls. Inter-observer variability of the mean testicular tissue elasticity was excellent (Intraclass correlation coefficient: 0.939, p < 0.001). Median time between testicular detorsion and follow-up ultrasound examination was 18 months (range, 11-36 months). Torsion side, torsion degree, and pain duration were recorded, and testicular volumes were calculated. The study population comprised 24 patients (48 testes) with a mean age of 21.1 ± 7.8 years. The mean testicular volume was measured as 12.3 ± 5.4 ml for the testicular salvage group, 13.9 ± 3.8 ml for the contralateral testes, and 13.7 ± 2.7 ml for the control group (p = 0.553). The mean testicular speed mode values were higher in the testicular salvage group (1.34 ± 1.21 m/s) compared with the contralateral testes group (1.00 ± 0.08 m/s), and the control group (1.01 ± 0.06 m/s), however there was no statistically significant difference between the three groups (p = 0.861). While testicular atrophy was detected in three patients, an intraparenchymal wedge-shaped focal hypoechoic area developed after torsion in a further three patients. The elastography examination for focal hypoechoic areas revealed an increase or decrease in tissue stiffness compared to the normal parenchyma. The tissue stiffness values of the testicular salvage group were higher in complete torsion compared to incomplete torsion. The elastography method contributes to other imaging methods in distinguishing focal lesion areas that can be seen after testicular torsion from malignant conditions. Elastography presents as a feasible and practical complementary modality for the follow-up of testicular salvage after torsion.

LOCAL-IGF-1 and GH application IMPROVES germ cell histology, spermatogenesis and fertility after experimental testicular torsion and detorsion.

OBJECTIVE: To evaluate the impact of insulin like growth factor-1(IGF-1) and growth hormone (GH) on testis histology, spermatogenesis, and fertility in prepubertal rats exposed to 6 h of testicular torsion (TT) and detorsion. MATERIAL-METHOD: Forty-eight male Wistar-albino rats weighing 30-70g and at 3-week age were allocated into six groups involving eight rats in each group as follows: Group 1:Sham, Group 2:Control, Group 3:Gelatin, Group 4:Local-IGF-1, 5: Local-GH, Group 6: Systemic-GH. Right testis was only exposed and sutured in the sham group, and right testes were rotated clockwise, 720°, fixed, and 6 h later, detorsion on the testis was done in groups 2-6. Unloaded gelatin, 5 µg local-IGF-1 loaded, and 2IU rhGH loaded gelatin were sutured to the right testis after detorsion in groups 3-5. In Group 6, 0.3IU/100gr/d rhGH was given for seven days via subcuticular route after detorsion. Each of the rats cohabited with two female rats five weeks later. Afterward, both right and left testes were removed. Mean diameter of seminiferous tubules (STD), mean biopsy score count of the testis (TBSC), mean percentage of haploid cells (HCP) were assessed, and fertility parameters were evaluated. RESULTS: STD and TBSC of the ipsilateral testes were significantly reduced in control and gelatin groups when compared to sham, local-IGF-1, and local-GH groups. STD and TBSC of the ipsilateral testes of the systemic-GH group were decreased compared to the sham group. HCP of the ipsilateral testes of control, gelatin, and systemic-GH groups were significantly lower than the sham, local-IGF-1, and local-GH groups. STD, TBSC, and HCP of the contralateral testes were significantly reduced in control and gelatin groups when compared separately to sham, local-IGF-1, systemic- GH, and local-GH groups. The difference between groups regarding potency, fertility, fecundity indexes, and mean fetus numbers were not significant. CONCLUSION: Even though there was significant and permanent histologic germ cell damage and reduced HCP in both ipsilateral and contralateral testes, experimental 6 h TT and detorsion in prepubertal rats did not have a negative impact on future fertility. Local-IGF-1and rhGH treatment improved germ cell histology and spermatogenesis in both ipsilateral and contralateral testes of prepubertal rats, subjected to 6 h of TT and detorsion.

Long-term effects of orchiopexy and orchiectomy on the testes of rats with testicular torsion.

INTRODUCTION: Ischemia/reperfusion injury occurs after testicular torsion, levels of free oxygen radicals and inflammatory cytokines are increased in both the torsional and contralateral testis, leading to testicular injury. OBJECTIVE: The present study investigated whether orchiopexy or orchiectomy after testicular torsion was superior in terms of fertility potential in the long term. STUDY DESIGN: Following 720°, 4 h left testicular torsion, orchiectomy or orchiopexy was performed on 84 rats, which were then sacrificed and evaluated for testicular function at day 1, at 3 months and 6 months (n = 14 per group). An additional 14 rats were in the control group. RESULTS: Follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were significantly lower in the orchiopexy group than the orchiectomy and control groups after 3 months. However, there were no significant differences in hormone parameters among the three groups after 6 months. The hormone levels, Johnsen score, seminiferous tubule diameter, and inducible nitric oxide synthase (iNOS) expression at 3 and 6 months were not significantly different between the orchiectomy group and controls. Histopathological analyses at 3 and 6 months indicated significant decreases in Johnsen score and seminiferous tubule diameter in the ipsilateral testis in the orchiopexy group. At 3 months, the level of iNOS expression in the contralateral testis was significantly lower in the orchiopexy group than in other groups. At 6 months, however, it was not significantly different between the orchiopexy and control groups. There were no significant differences in iNOS expression at 3 or 6 months in the orchiectomy group compared to controls. DISCUSSION: The ipsilateral testis in the orchiopexy group began to atrophy at 3 months, and the degree of atrophy became more evident at 6 months. The level of iNOS expression was low in the bilateral testis at 3 months in the orchiopexy group, and sperm in the contralateral testis were not yet functionally healthy. The level of iNOS expression in the ipsilateral testis decreased further at 6 months in the orchiopexy group, while that in the contralateral testis returned to the normal level. CONCLUSION: Testicular functions were restored faster after orchiectomy compared to orchiopexy following testicular torsion. However, follow-up of the rats for 6 months demonstrated that orchiopexy or orchiectomy procedures conducted on the testicular torsion had no effect on future fertility potential after 4 h of torsion.

Idebenone regulates sirt1/Nrf2/TNF-α pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats.

Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i. p) without T/D; (3) the T/D group: rats underwent torsion for 2 h and detorsion for 4 h; and (4) the IDE+ T/D group: rats received IDE 1 h before T/D. Testicular malondialdehyde (MDA), total nitrite/nitrate (NOx), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), caspase-3, sirtuin type 1 (Sirt1), serum interleukin-1ß (IL-1ß), total cholesterol, and testosterone were measured. Histological changes, nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2), and proliferating cell nuclear antigen (PCNA) immuno-expressions were assessed. T/D displayed an increase in MDA, NOx, TNF-α, caspase-3, IL-1ß, and total cholesterol with a significant decrease in TAC, Sirt1, and testosterone and strong positive Nrf2 and negative PCNA immuno-expressions. IDE could improve all oxidative, inflammatory, and apoptotic indicators. Therefore, IDE significantly reduced testicular ischemia-reperfusion injury in the juvenile rat testicular T/D model by limiting oxidative stress, inflammation, and apoptosis via the Sirt1/Nrf2/TNF-α pathway.

Effect of Cerium Oxide on Kidney and Lung Tissue in Rats with Testicular Torsion/Detorsion.

Introduction: Testicular torsion is a surgical emergency that results in testicular ischemia as a result of rotation of the spermatic cord around itself. Oxidative damage occurs in the testis and distant organs with the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. In this study, we aimed to investigate the effects of cerium oxide (CeO2), an antioxidant nanoparticle, on lung and kidney tissues in testicular torsion/detorsion (T/D) in rats. Materials and Methods: After ethics committee approval, 24 rats were equally (randomly) divided into 4 groups. Left inguinoscrotal incision was performed in the control (C) group. In group CeO2, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before inguinoscrotal incision. In group T/D, unilateral testicular T/D was achieved by performing an inguinoscrotal incision and rotating the left testis 720° clockwise, remaining ischemic for 120 minutes, followed by 120 minutes of reperfusion. In group CeO2-T/D, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before testicular T/D. At the end of the experiment, lung and kidney tissues were removed for histopathological and biochemical examinations. Results: Glomerular vacuolization (GV), tubular dilatation (TD), tubular cell degeneration and necrosis (TCDN), leukocyte infiltration (LI), and tubular cell spillage (TCS) in renal tissue were significantly different between groups (p = 0.012, p = 0.049, p < 0.003, p = 0.046, and p = 0.049, respectively). GV and TCDN were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.042 and p = 0.029, respectively). Lung tissue neutrophil infiltration, alveolar thickening, and total lung injury score (TLIS) were significantly different between groups (p = 0.006, p = 0.001, and p = 0.002, respectively). Neutrophil infiltration and TLIS were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.013 and p = 0.033, respectively). Lung and kidney tissue oxidative stress parameters were significantly different between groups (p < 0.05). Renal tissue glutathione-s-transferase (GST), catalase (CAT), and paraoxonase (PON) activities were significantly higher, and malondialdehyde (MDA) levels were significantly lower in group CeO2-T/D than in group T/D (p = 0.049, p = 0.012, p < 0.001, and p = 0.004, respectively). GST and PON activities were higher, and MDA levels were lower in group CeO2-T/D than in group T/D in the lung tissue (p = 0.002, p < 0.001, and p = 0.008, respectively). Discussion. In our study, cerium oxide was shown to reduce histopathological and oxidative damage in the lung and kidney tissue in a rat testis torsion/detorsion model.

Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model.

The protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-α and NF-κB levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. PRACTICAL APPLICATIONS: Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.

Histopathological effects of ß-hCG and vitamin C on the detorsioned testicle in rats with unilateral testicular torsion.

BACKGROUND: Testicular torsion is still an urgent surgical condition and without any treatment it can cause infertility. The main pathophysiology of testicular torsion ischaemic injury however; the main sequalae of detorsion is reperfusion injury. Furthermore; treatments to prevent ischemic reperfusion injury due to decreased blood flow are important to preserve testicular function. AIMS: Human chorionic gonadotropin ß (ß-hCG) is an anabolic hormone that supports steroidogenesis and spermatogenesis. Vitamin C (Vit-C) is one of the water-soluble vitamins and is also a potent antioxidant in ischemic damage. Moreover, it has protective effects by increasing blood and lymph flow in the testicles. The aim of this study is to investigate the effects of ß-hCG, Vit-C and their combination on ischemic reperfusion injury occurring after surgical treatment of testicular torsion. STUDY DESIGN: Animal research studies. METHODS: The study was performed on 25 male Wistar albino rats. The animals were divided equally into 5 groups. In the first group "Control Group," left orchiectomy was performed. In the second group "Sham Group," a 720° clockwise torsion was created and after 4 h of left testicular torsion it was detorsioned for 4 h and then left orchiectomy was performed. In the third group same procedure was applied with 30 mg vitamin C was administered via intraperitoneal route once a week for 3 weeks. In the fourth group after same surgical procedures 75 IU ß-hCG was administered via intraperitoneal route once a week for 3 weeks. In the fifth group after 4 h left testicle torsion it was detorsioned for 4 h then, 75 IU ß-hCG and vitamin C together were administered via intraperitoneal route once a week for 3 weeks. Left orchiectomy was performed after 3 weeks in the third, fourth and fifth groups. Specimens were evaluated histologically. RESULTS: Testicular tissue histopathological evaluations were performed. A high histopathological stage indicates more testicular damage, and a low one was indicated less testicular damage. The average histopathological grade of vitamin C + ß-hCG group was significantly higher than the average histopathological grade of the control, the sham group and vitamin C group. The average histopathological grade of the vitamin C group was significantly lower than the average histopathological grade of sham and ß-hCG groups. The ratio of the testicular atrophy of the Vitamin C + ß-hCG group (100%) was higher than sham (40%) and ß-hCG (40%) groups with a significant difference. A significant statistical difference was found among all groups histopathological grades of testicular tissue. CONCLUSION: In animals taking vitamin C, an improvement of histopathological findings and a significant decrease in histological stages has been provided. However, it was observed that the histological findings of ß-hCG and ß-hCG + vitamin C groups worsened. It was found that ß-hCG increased oxidative damage in the testicles and this damage can be so severe that exceeding the capacity of potent antioxidants such as Vitamin C. We believe that ß-hCG can be harmful to testicles exposed to oxidative damage.

Effect of Chrysin on Endoplasmic Reticulum Stress in a Rat Model of Testicular Torsion.

BACKGROUND: The purpose of this study was to evaluate the possible therapeutic effect of chrysin (CHS) on testicular torsion/detorsion (T/D) injury in vivo through the mechanisms of oxidative stress and endoplasmic reticulum stress (ERS). METHODS: Eighteen male rats were divided into three groups of six subjects in each group: control, T/D and T/D + CHS (100 mg/kg). To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using an ELISA kit. To evaluate the degree of ERS, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it is determined that statistically significant decreasing in the levels of TAS, SOD and Johnsen score, and increasing in TOS, MDA, GRP78, ATF6 and CHOP levels compared to control group (p < 0.05). CHS administration statistically significantly restored this T/D-induced damage (p < 0.05). CONCLUSION: This is the first study to show that CHS prevent T/D-induced testicular damage through its ERS inhibitor activity. More comprehensive studies are needed to understand the underlying mechanisms.Supplemental data for this article is available online at https://doi.org/10.1080/08941939.2021.2015489 .

Apoptotic balance during testicular detorsion after one hour induced torsion in rats.

Testicular torsion (TT) is an emergency complication that leads to oxidative stress and adversely affects spermatogenesis. Although immediate treatment consists of testicular detorsion (TD) to reverse TT-induced ischemia, mechanisms underlying recovery have yet to be fully understood. The current study aimed to investigate TD effects after a one-hour experimental TT by evaluating testicular antioxidant status and apoptosis-related proteins. Forty male Wistar rats were submitted to TT by testicular rotation, for one hour. Following TT, 32 rats were submitted to TD for 1, 2, 4, and 8 h (N = 8/group), the other 8 rats euthanized as TT-only. For controls, 8 rats were sham-operated. Testicular tissues were aseptically dissected for biochemical, histopathological, and immunohistochemistry analyses. The TD groups, especially after 4 h of TD, exhibited diminished MDA and increased TAC and GPX levels in testicular tissue. Levels of p53 and Caspase-3 were down-regulated in T1D4 and T1D8 groups versus torsion group. Bcl-2 was increased in T1D4 and T1D8 groups compared to the TT group. Moreover, spermatogenesis was recovered in T1D4 and T1D8 groups compared to the TT group. It can be concluded that after 1 h TT in rats, at least 4 h post-TD is needed for testicular tissue to initiate recovery.

Astaxanthin Protects Testicular Tissue against Torsion/Detorsion-Induced Injury via Suppressing Endoplasmic Reticulum Stress in Rats.

BACKGROUND: The aim of this study was to investigate the effects of astaxanthin (ASX) on testicular torsion/detorsion (T/D) damage in rats in terms of oxidative stress and endoplasmic reticulum (ER) stress. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups with six rats in each group: control, T/D and T/D + 20 mg/kg ASX. Torsion and detorsion times were applied as 4 h and 2 h, respectively. ASX application was performed 30 minutes before detorsion. At the end of the period, testicular tissues were removed and biochemical and histological analyzes were performed. To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using ELISA kit. To evaluate the degree of ER stress, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it is determined that statistically significant decreasing in TAS, SOD levels and Johnsen score, and increasing in TOS, OSI, MDA, GRP78, ATF6 and CHOP levels (p < 0.001) compared with control group. ASX administration statistically significantly restored this T/D-induced damage (p < 0.01). CONCLUSION: This is the first study to show that ASX prevent T/D-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms.