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.

Testicular torsion in vivo models: Mechanisms and treatments.

BACKGROUND: Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. OBJECTIVES: To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. MATERIALS AND METHODS: We reviewed all original research and epidemiological papers related to testicular torsion condition. RESULTS: Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. DISCUSSION AND CONCLUSION: To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.

Omega-3 fatty acid rescues ischaemia/perfusion-induced testicular and sperm damage via modulation of lactate transport and xanthine oxidase/uric acid signaling.

This study aimed to explore the potential antioxidant, anti-inflammatory, and anti-apoptotic effects of omega 3 fatty acid (Ω-3) in a rat model of testicular torsion/detorsion (T/D). Under ketamine/xylazine anaesthesia, age-matched adult male Wistar rats of comparable weight underwent sham-operation or testicular torsion by fixing the left testis rotated at 720° for two and half hours. After detorsion, animals were treated with either olive oil as vehicle or Ω-3 subcutaneously for three days. On post-operative day 3, rats were culled and the ipsilateral and contralateral testes, as well as obtained blood samples, were analyzed. Our findings revealed that T/D led to significant poor weight gain, distorted gross anatomy, and cytoarchitecture of the testes, low sperm quality, redox imbalance, and inflammation of the ipsilateral and contralateral testes. This was accompanied by reduced circulatory testosterone, a decline in testicular lactate metabolism and transport, upregulation of xanthine oxidase/uric acid signaling, and increased testicular DNA fragmentation. Administration of Ω-3 attenuated T/D-induced damage to the testes and sperm cells with a significant rise in the level of serum testosterone. Enhancement of lactate transport and down-regulation of xanthine oxidase/uric acid signaling by Ω-3 may be beneficial in protecting against T/D-related oxido-inflammatory damage and male infertility.

The protective effect of Ganoderma lucidum on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury.

PURPOSE: To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. METHODS: Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. RESULTS: G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. CONCLUSION: The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.

The protective effect of Ganoderma lucidum on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury

Abstract Purpose To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. Methods Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. Results G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. Conclusion The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.

Protective effect of tadalafil and verapamil on testicular function and oxidative stress after torsion/detorsion in adult male rat.

OBJECTIVE: This study used a rat model to investigate the protective effect of tadalafil and verapamil on testicular function and oxidative stress after torsion/detorsion. METHODS AND MATERIALS: Animals were randomly divided into five groups: G1, Sham group; G2, testicular torsion followed by detorsion (TD); G3, testicular torsion/detorsion received 0/4 mg/kg of tadalafil (TDT); G4, testicular torsion/detorsion received 0/1 mg/kg of verapamil (TDV); and G5, testicular torsion/detorsion received 0/1 mg/kg of verapamil and 0/4 mg/kg of tadalafil (TDTV). All treated groups were received the treatment 30 min before detorsion. Also, after reperfusion period (24 hr), the parameters of spermatozoa were assayed, and blood was measured for oxidative stress markers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), activity of malondialdehyde (MDA) and blood levels of testosterone. The histological parameters investigated by Johnson's scores (JS), and also the seminiferous tubule diameter (STD) and the height of the germinal epithelium (HE) were measured using the linear eyepiece grids on the light microscope. RESULTS: Between Sham and other groups were observed a significant change in histological parameters. Also, the levels of SOD, GPx and testosterone hormone were significantly decreased in TD while these increased in therapeutic groups. In the duration of ischaemia, the MDA level increased. Treatment with tadalafil and verapamil decreased the MDA level in treatment groups and also observed a significant change in sperm parameters between Sham and other groups. CONCLUSIONS: Tadalafil and verapamil can be protected the testis tissue damage and replaced the testicular function by suppressing oxidative stress after testicular torsion.

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats.

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl-2 genes, and apoptosis index of germ cells after testicular torsion-detorsion (ischaemia-reperfusion, IR) injury model in rats. Twenty-eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion-detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl-2, level of serum testosterone hormone and antioxidant parameters-GPx and SOD-were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion-detorsion.

Protective Effects of Hypericum perforatum and Quercetin in a Rat Model of Ischemia/Reperfusion Injury of Testes.

PURPOSE: This study aimed to compare the protective effects of Hypericum perforatum (Hp) and quercetin, a flavonoid, against ischemia/reperfusion (I/R) injury in rat testes. MATERIALS AND METHODS: This study included 28 male Wistar albino rats that were divided into four groups. Except for the sham group, torsion was created by rotating both testes at an angle of 720 degrees clockwise for 2 hours. The Hp and quercetin groups received 25 mg/kg Hp and quercetin intraperitoneally 30 minutes before detorsion, respectively. Orchiectomy was performed for the measurement of markers of oxidative stress and histopathological examination. RESULTS: In the Hp and quercetin groups, malondialdehyde (MDA) and nitric oxide (NO) levels and total oxidant capacity were significantly lower, the glutathione level and total antioxidant status were significantly higher, and Johnsen's testis biopsy scores were significantly higher than in the torsion/detorsion group (p ˂ 0.001). The markers of oxidative injury were significantly lower (p ˂ 0.001) and total antioxidant status was significantly higher (p ˂ 0.001), except for glutathione (p = 0.62) in the Hp group than in the quercetin group. Johnsen's score between Hp and quercetin groups was not significantly different (p = 0.80). CONCLUSION: Both Hp and quercetin have protective effects against I/R injury of the testes, but the protective effect of Hp was found to be stronger than that of quercetin.

Effects of pomegranate peel extract on histopathology, testosterone levels and sperm of testicular torsion-detorsion induced in adult Wistar rats.

Background In the present study, effects of pomegranate peel extract have been evaluated on decreasing the damage induced by testis torsion. Methods In this study, 30 adult Wistar rats were randomly divided into three groups of control, experimental (1) and experimental (2). CONTROL: no ischemia, received vehicle alone, exposed to sham operation. Experimental (1): Received the vehicle alone during ischemia followed by 60 days' reperfusion. Experimental (2): After performing ischemia reperfusion, 500 mg/kg of pomegranate peel extract has been used for 60 days. Blood samples and sperm samples were collected. Testes were harvested and stained with haematoxylin and eosin to study the structure of seminiferous tubules. Results The statistical comparison between sperm count and their viability and testosterone hormone amount showed a significant difference between control and experimental (1) groups and control and experimental (2) groups. The results showed an improvement of morphological condition of seminiferous tubules. Conclusions Pomegranate peel extract has revealed desirable changes on the effective parameters in infertility.

[Protective effect of Danxuetong injection against testicular injury after testis torsion/detorsion in rats].

OBJECTIVE: To investigate the protective effect of Danxuetong injection (DXT, a combination of Danshen and Xueshuantong injections) against testicular ischemia-reperfusion injury following testis torsion/detorsion in rats. METHODS: Thirty-two 4-week-old healthy male SD rats were randomly divided into four groups of equal number: sham operation, normal saline, single DXT injection, and successive DXT injection. The rat models of testicular ischemia-reperfusion injury were established by 2-hour 720-degree torsion/detorsion of the unilateral testis. At 6 weeks after modeling, the rats were killed and their testes were harvested for measure- ment of testicular coefficients, sperm counts, sperm motility, and the levels of total anti-oxidative capacity (T-AOC) , superoxide dismutase (SOD) , nitric oxide synthase (NOS) , and malondialdehyde ( MDA) in the testis tissue. RESULTS: Compared with the rats of the normal saline group, those of the single DXT injection and successive DXT injection groups showed significant increases in the testicular coefficient (0.11 ± 0.03 vs 0.35 ± 0.04 and 0.40 ± 0.06, P < 0.05), sperm count ([0.46 ± 0.10] vs [1.44 ± 0.50] and [3.00 ± 1.28] x10(9)/ml, P < 0.05), sperm motility ([13.63 ± 14.04] vs [39.63 ± 5.04] and [76.31 ± 3.67]%, P < 0.05), the activity of SOD (72.76 ± 5.58 vs 116.25 ± 8.83 and 133.20 ± 13.84, P < 0.05), and the level of T-AOC (5.58 ± 1.07 vs 13.34 ± 5.81 and 19.21 ± 5.69, P < 0.05), but a remarkable decrease in the content of MDA (42.38 ± 8.94 vs 20.94 ± 5.65 and 15.02 ± 1.03, P < 0. 05) in the injured testes. CONCLUSION: DXT can effectively rid the testis tissue of oxygen free radicals, improve sperm count and motility by antioxidation, and protect the testis tissue of prepubertal rats against testicular ischemia-reperfusion injury after testis torsion/detorsion. It also has a protective effect on the contralateral testis, and successive injection has a better effect than single injection of DXT.

[Protective effect of tadalafil against ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats. METHODS: Eighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope. RESULTS: At 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A. CONCLUSION: Tadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.

Mechanisms of testicular torsion and potential protective agents.

Testicular torsion is a urological emergency most commonly seen in adolescence, involving a decrease in blood flow in the testis resulting from torsion of the spermatic cord that can result in gonad injury or even loss if not treated in time. Testicular ischaemia-reperfusion injury represents the principle pathophysiology of testicular torsion, with ischaemia caused by twisting of the spermatic cord, and reperfusion on its subsequent release. Many cellular and molecular mechanisms are involved in ischaemia-reperfusion injury following testicular torsion. Studies have investigated the use of pharmacological agents as supportive therapy to surgical repair in order to prevent the adverse effects of testicular torsion. Numerous substances have been proposed as important in the prevention of post-ischaemia-reperfusion testicular injury. A range of chemicals and drugs has been successfully tested in animal models for the purpose of mitigating the dangerous effects of ischaemia-reperfusion in testis torsion.

The short term effects of resveratrol on ischemia-reperfusion injury in rat testis.

PURPOSE: The purpose of this study was to identify changes taking place in the rat testis at the 24th hour of reperfusion following testicular torsion and to evaluate the effects of resveratrol (RSV), a powerful antioxidant, in preventing these changes using novel biochemical parameters and histopathology. METHODS: Eighteen adult male rats were divided into three groups: Sham-operated (S), torsion/detorsion (T/D), and T/D+RSV groups. In the T/D group, testicular ischemia was achieved by rotating the left testis 720° clockwise for 4h. In the T/D+RSV group, 20mg/kg RSV was administered intraperitoneally 30 min before detorsion. All rats were sacrificed 24h after detorsion. Serum and tissue malondialdehyde (MDA) concentrations, ischemia modified albumin (IMA), total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were analyzed. RESULTS: Serum MDA, IMA, TOS, and OSI levels rose significantly in the T/D group. Serum MDA and IMA values were lower in the T/D+RES groups, but not significantly. OSI and TOS values were lower in the T/D+RES group, and the difference was significant. TAS values decreased significantly in the T/D group and rose in the T/D+RSV group, but not significantly. Ipsilateral tissue MDA values were significantly elevated in the T/D group and decreased in the T/D+RSV group, but not significantly. Apoptosis and histopathological damage increased significantly in the T/D group and decreased significantly in the T/D+RSV group. In the contralateral testis, apoptosis increased significantly in the T/D group. It decreased significantly in the T/D+RSV group. CONCLUSIONS: Our findings show that RSV had a protective effect against oxidative damage induced with a testicular T/D model, especially at the antiapoptotic and histopathological level. OSI may be a good guide to the clinical status of testicular T/D.

The effects of carvedilol on ischemia-reperfusion injury in the rat testis

Objective: To analyze the oxidative damage and histopathological alterations caused by ischemia-reperfusion (I/R) injury and ameliorative effects of carvedilol (CVD) in the rat testis. Materials and Methods: Twenty-one male rats were randomized into 3 groups as follows: Group I (n = 7); control (sham) group, Group II (n = 7); I/R group, in which I/R injury was performed by torsing the left testis 720º clockwise for 2 hours and detorsing for 2 hours. Group III (n = 7); CVD treatment group; in addition to I/R process, one-dose of CVD was administered (2mg/kg, i.p) 30 min. before detorsion. Levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and levels of malondialdehyde (MDA) and protein carbonyl (PC) were determined in testicular tissues and serum of rats. Testicular tissues were also examined histopathologically and Johnsen scores were determined. Results: Activities of SOD and GSH-Px in serum and testicular tissues were increased by I/R, but administration of CVD decreased these levels (p < 0.001 and p = 0.001). Significantly increased MDA levels in serum and testicular tissues were decreased by CVD treatment (p < 0.001 and p = 0.001). Concerning PC levels in serum and testicular tissues, there was no statistically significant difference between the groups (p = 0.989 and p = 0.428). There was not a statistically significant difference in terms of mean Johnsen scores between the groups (p = 0.161). Conclusions: Administration of CVD decreased oxidative damage biochemically in the rat testis caused by I/R injury, but histopathologically no change was observed between all of the groups. .

Comparison of melatonin and ozone in the prevention of reperfusion injury following unilateral testicular torsion in rats.

OBJECTIVE: To compare the efficacy of ozone with melatonin, shown as the most powerful antioxidant in attenuation of testicular ischemia/reperfusion injury, in an experimental rat model of testicular torsion/detorsion. METHODS: Twenty-four male Wistar rats were divided into 4 groups: sham-operated, torsion/detorsion, torsion/detorsion plus melatonin, and torsion/detorsion plus ozone. Melatonin (10 mg/kg) and ozone (4 mg/kg) were intraperitoneally injected daily beginning 15 minutes before detorsion for the following 7 days. At the seventh day, blood and tissue samples were obtained. Johnsen score, malondialdehyde, inhibin B, glutathione plasma total sulfhydryl group (RSH) levels, and total nitric oxide were studied. RESULTS: Torsion/detorsion caused increase in tissue malondialdehyde and total nitric oxide along with a decrease in Johnsen score, tissue and plasma inhibin B, RSH, and glutathione levels. Melatonin prevented the rise in malondialdehyde and total nitric oxide levels and improved Johnsen score, tissue and plasma inhibin B, and tissue glutathione levels, along with a decrease in plasma RSH level. Ozone showed similar results except for the total nitric oxide level. Concomitantly, in contralateral testis, melatonin and ozone induced similar changes for Johnsen score, malondialdehyde, and inhibin B (not significant) and in glutathione (significant). Melatonin decreased the total nitric oxide level in both testes and ozone increased the same parameter. CONCLUSION: On different pathways, ozone was comparable with melatonin in the amelioration of ischemia/reperfusion injury. Protective effects of ozone were associated with nitrous oxide. The potential for ozone as a treatment for torsion/detorsion therefore deserves to be further elucidated.

Protective effects of Ginkgo biloba (EGb 761) on testicular torsion/detorsion-induced ischemia-reperfusion injury in rats.

The aim of this study was to investigate the protective effect of Ginkgo biloba (EGb 761) on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups: control, I/R and I/R treated with EGb 761; each group contains 8 animals. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion. EGb 761 (50 mg/kg, orally) was administrated only once, 40 min prior to detorsion. To date, no more histopathological changes on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury in rats by EGb 761 treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in I/R groups were compared to the control group. Furthermore, EGb 761 treated animals showed an improved histological appearance in I/R group. Our data indicate a significant reduction in the activity of TUNEL and endothelial nitric oxide synthase (eNOS) in testes tissue of I/R treated with EGb 761 therapy. Electron microscopy of the testes of rats demonstrated that EGb 761 pretreatment was particularly effective in preventing the mitochondrial degeneration, dilatation of SER and enlarged intercellular spaces in both Sertoli and spermatid cells in I/R treated animals. We believe that further preclinical research into the utility of EGb 761 may indicate its usefulness as a potential treatment on testes injury after I/R in rats.

Protective effect of rutin on testicular ischemia-reperfusion injury.

PURPOSE: The pathophysiology of testicular torsion-detorsion is an ischemia-reperfusion injury caused by overgeneration of reactive oxygen species (ROS). This study aimed to investigate the effect of rutin, a well-known antioxidant, on testicular ischemia-reperfusion injury. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 3 groups, each containing 20 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720° for 2 hours. Rats in the treatment group received the same surgical procedure as the torsion-detorsion group, but rutin was administered intravenously at the time of detorsion. Bilateral orchiectomy was performed on half of the rats in each experimental group at 4 hours after detorsion for measurement of malondialdehyde, an indicator of intratesticular ROS content, and for evaluation of superoxide dismutase and catalase, which are endogenous antioxidant enzymes. Orchiectomy was performed on the remaining rats at 3 months after detorsion for analysis of testicular spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion caused a significant increase in malondialdehyde level and caused significant decreases in superoxide dismutase, catalase activities, and spermatogenesis in ipsilateral testes. The rats treated with rutin had a significant decrease in malondialdehyde level and had significant increases in superoxide dismutase, catalase activities, and spermatogenesis in ipsilateral testes, compared with torsion-detorsion group. CONCLUSIONS: Rutin protects testes from ischemia-reperfusion injury. The protective effect of rutin may be caused by scavenging ROS by increasing superoxide dismutase and catalase activities.

Psoralea corylifolia protects against testicular torsion/detorsion-induced ischemia/reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiology of testicular torsion-detorsion is ischemia-reperfusion injury of the testis. In the course of testicular ischemia and reperfusion, overgeneration of reactive oxygen species is a major initiating component of the testicular spermatogenic injury. Reactive oxygen species regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The transcription factor cAMP-responsive element modulator-τ (CREMτ) plays an essential role in spermatogenesis. Psoralea corylifolia, a medicinal herb with anti-oxidative activity, has been used to treat male reproductive dysfunction in traditional Chinese medicine. In this study, we investigated the effect of Psoralea corylifolia on testicular torsion/detorsion-induced injury. MATERIALS AND METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into 3 groups, each containing 20 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720° for 2h. Rats in the treatment group received the same surgical procedure as the torsion-detorsion group, but Psoralea corylifolia was administered orally. Bilateral orchiectomy was performed on half of the rats in each experimental group at 4h after detorsion for measurement of malondialdehyde which is an indicator of intratesticular reactive oxygen species content. Orchiectomy was performed on the remaining rats at 3 months after detorsion for analysis of testicular CREMτ expression and spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion caused a significant increase in malondialdehyde level and caused significant decreases in CREMτ expression and spermatogenesis in ipsilateral testes. Psoralea corylifolia treatment significantly decreased malondialdehyde level and significantly increased CREMτ expression and spermatogenesis in ipsilateral testes, compared with torsion-detorsion group. CONCLUSIONS: These results suggest that Psoralea corylifolia may protect testicular spermatogenesis by enhancing CREMτ expression by scavenging reactive oxygen species.

Effect of curcumin on ipsilateral and contralateral testes after unilateral testicular torsion in a rat model.

OBJECTIVE: The aim of the study was to determine the protective effect of curcumin on testicular ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS: 32 male rats were divided into four groups (n = 8): group 1: control; group 2: ischemia; group 3: I/R, and group 4: I/R+CUR. Curcumin (150 mg/kg, p.o.) was administered before 30 min of reperfusion in group 4. Malondialdehyde (MDA) levels, Johnsen's testicular biopsy scores, and mean seminiferous tubule diameter measurements were evaluated in testes. In addition, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expressions were evaluated immunohistochemically. RESULTS: MDA levels in control groups were significantly lower than other groups in ipsilateral and contralateral testes. Johnsen's scores in the control group were significantly higher than in other groups. MDA levels and Johnsen's scores in the I/R+CUR group were similar to the ischemia and I/R groups in ipsilateral and contralateral testes. The immunoreactivity of iNOS and eNOS were increased in I/R ipsilateral testicular groups. After I/R, iNOS and eNOS expression increased slightly in contralateral groups. Additionally, the curcumin treatment decreased iNOS and eNOS immunoreactivity in ipsilateral and contralateral testes. CONCLUSION: The results suggest that curcumin did not protect the unilateral nor contralateral testes. This observation may depend on inhibition of iNOS and eNOS due to inhibition of the antioxidant, anti-inflammatory effects of nitric oxide.