Nitroglycerin ameliorates sperm parameters, oxidative stress and testicular injury following by testicular torsion/detorsion in male rats.

PURPOSE: This study was designed to determine the probable protection mechanisms of nitroglycerin, a widely used medication for treatment of heart failure and angina, in amelioration of testicular ischemia/reperfusion damage. METHODS: 24 adult male rats were randomly divided into three equal groups; with eight rats in each group: Group 1 (Sham) was sham-operated. Group 2 (T_D): 2 h testicular torsion was induced, afterward detorsion was performed and maintained for 2 h. Group 3 (NG): Nitroglycerin was administered immediately after detorsion. Sperm quality parameters such as viability, motility, morphology, and concentration, levels of antioxidant enzymes (glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC)), and amount of malondialdehyde (MDA) in the blood plasma were examined in each group, thereafter histopathological parameters including germinal epithelial cell thickness (GECT), mean seminiferous tubular diameter (MSTD), Johnson's score and Cosentino's score were assessed. RESULTS: Testicular T_D significantly reduced sperm viability, motility, and normal morphology, whereas the NG administration remarkably increased the percentage of live, motile, and normal spermatozoa (p < 0.05). Levels of GPx, CAT, and TAC significantly reduced and the MDA level significantly increased in the T_D group in comparison to the sham group (p < 0.05). The NG treated group demonstrated significantly reduced MDA concentrations as well as elevated levels of GPx and CAT compared to the T_D group (p < 0.05). Induction of testicular torsion significantly reduced Johnson's score, GESCT (µm), and MSTD (µm), and remarkably increased the Cosentino's score (P < 0.05), while NG injection significantly increased Johnson's score, GESCT (µm), and MSTD (µm) and reduced the Cosentino's score (P < 0.05). CONCLUSION: According to the findings in this research, nitroglycerin was able to protect the testicular tissue from ischemia-reperfusion damage caused by induced torsion/detorsion.

[A Case of Prenatal Testicular Torsion].

We report a prenatal case of neonatal testicular torsion. A 0-day-old boy with left scrotal swelling from the time of birth was referred to us. The physical examination revealed left intrascrotal hard mass. The ultrasonography with doppler color flow showed heterogeneous parenchymal echogenicity and the lack of blood flow to the affected testis. Testicular torsion was suspected and emergent surgical exploration was performed. The left testis was necrotic with extravaginal torsion of the spermatic cord. Left high orchiectomy was performed, considering the possibility of inguinal hernia. The histopathological examination confirmed the necrosis of the left testis.

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.

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.

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 .

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.

Neonatal testicular torsion: a systematic literature review.

Neonatal testicular torsion (NTT) is rare and reported salvage rates vary widely both in their cited frequency and plausibility. The timing and necessity of surgery is controversial with different centers arguing for the conservative management of all cases while others argue for prompt exploration for all. Confusion also reigns over the need to fix the contralateral testis. In order to clarify the issue the authors reviewed the literature and found 18 case series of NTT, containing 268 operated cases suitable for analysis. This paper reviews the literature on NTT specifically regarding salvage rates and timing/necessity of surgery. Its primary aim is to produce an overall salvage rate in the operated group. Overall salvage rate was 8.96%, 24 testes. When operation is specified as an emergency, salvage may be as high as 21.7%. While salvage of a testis torted at birth is rare, it is reported. Early asynchronous torsion is also rare but reported. Worryingly, bilateral torsion can present with unilateral signs.Given these findings, we would suggest early surgery with fixation of the contralateral side.

Adjuvant pharmacological and surgical therapy for testicular torsion: Current state of the art.

INTRODUCTION: Although the consequences of testicular torsion (TT) have been recognized for centuries, little progress has been made to improve outcomes beyond those seen with timely scrotal exploration. Even with testicular salvage, ischemia/reperfusion injury cause significant atrophy and functional impairment. Recent efforts have sought to identify adjuvant pharmacological or surgical interventions that may attenuate these consequences. In this review, we assess the evidence supporting clinical use of these nascent interventions. METHODS: We conducted a review of the literature published from 2000 to 2020, using the search terms "torsion", "testicular", "reperfusion", "ischemia", and "injury". Clinical and laboratory research focused on adjuvant pharmacological and surgical techniques mitigating torsion-associated injury in animal models and humans were identified. We recorded intervention timing/dose/route, and outcome timing/category through biomarkers of reperfusion injury, histology, and hormonal/reproductive function. RESULTS: Fifty-four FDA-approved agents, plus 52 herbal/investigational drugs, were reported in animal TT models. In every study, the investigated agents showed beneficial effects on measured endpoints compared to controls. Despite these universally promising animal findings, no pharmacological trials in humans were reported. Surgical techniques studied in animal models included decompression (tunica albuginea incision, TAI), "ischemic conditioning", and hypothermia. Only three human studies on surgical adjuvant maneuvers have been reported, all involving TAI; these showed potential benefit, but the level of evidence is low. CONCLUSION: There is preliminary evidence that adjuvant treatments may mitigate the effects of ischemia/reperfusion injury. However, the pool of investigated pharmacological agents is wide, yet remarkably shallow; most compounds have been reported in a single animal study. To advance this field, a mechanism-based approach should be used to select promising agents that can be tested systematically. This will determine treatment parameters that maximize safety, efficacy, and tolerability. Only then is it possible to move toward human trials. Adjuvant surgical methods such as TAI show promise in humans but require more robust clinical evaluation.

A rare emergency: testicular torsion in the inguinal canal.

Objectives. To report our experience and present the largest series of testicular torsion cases in the inguinal canal. Material and Methods. The clinical data of 13 patients with testicular torsion in the inguinal canal treated between 2005 and 2013 were reviewed. Recorded patient age, whether the testes were palpable or not, side of the affected testes, the presence of hernia, ischemia time, and operation outcomes were assessed. Results. Patient age ranged from 8 to 70 months (29.15 ± 20.22). Mean ischemia time was 16.5 ± 21.3 hours. Accompanying inguinal hernia was present in 92% of the cases (12/13). Four of the thirteen patients (30.8%) were treated by orchiectomy because the necrosis was present after prolonged ischemia time. Nine patients (69.2%) were treated by single session orchidopexy. Conclusion. Torsion of testes in the inguinal canal is a rare disease, but with rapid diagnosis, affected testes can be salvaged, but the key factor is to keep this condition in mind.

Intermittent testicular torsion.

Testicular torsion is the most common cause of acute scrotal pain in prepubertal and adolescent boys and should be foremost in the minds of primary care physicians evaluating these children. Intermittent testicular torsion is a separate entity that should be considered in all young males with a history of scrotal pain and swelling. Acute and intermittent sharp testicular pain and scrotal swelling, interspersed with long intervals without symptoms, are characteristic. Physical findings may include horizontal or very mobile testes, an anteriorly located epididymis, or bulkiness of the spermatic cord from partial twisting. Awareness of this entity and early elective orchiopexy will improve testicular salvage in patients with intermittent testicular torsion.

[Seminoma necrosis by testicular torsion]. / Seminomnekrose durch Hodentorsion.

The coincidence of a classical scrotal testicular torsion with a scrotal tumor is a rare event. In the case described here the classical histological characteristics of a seminoma were present in addition to clear signs of testicular torsion with fibrin-containing thrombi in the intratesticular capillaries, so that the ischemia time predicted by the pathologists correlated well with the clinical data of 7.5 h for the testicular torsion estimated at the time of the intervention. The intraoperative diagnosis made by the surgeon allowed a rapid response with only a semi-castration, excision of the wound edges and a highest possible amputation of the funiculus.

Bilateral anorchia in infancy: occurence of micropenis and the effect of testosterone treatment.

OBJECTIVE: To analyze the clinical and histological findings in boys with bilateral anorchia and the response to testosterone treatment on penis length. STUDY DESIGN: Patients were divided into two groups according to the absence (group A, n = 29) or the presence (group B, n = 26) of palpable intrascrotal or inguinal mass at first clinical examination. RESULTS: A micropenis was found in 46% of patients (n = 24) with a similar proportion in both groups. Testosterone treatment induced a mean penis length gain of 1.9 +/- 1.3 SDS (standard deviation score). However, micropenis persisted in six patients. Histological examination (n = 18) confirmed the absence of any testicular structure with deferent ducts being present unilaterally or bilaterally in all but three patients. In these three patients, a hemorrhagic testis, probably as a result of a mechanical torsion, was found. CONCLUSIONS: The presence of isolated micropenis in almost half of patients with bilateral anorchia strongly suggests that the testicular damage frequently occurs during the second half of gestation after male sexual differentiation. In most cases, testosterone treatment stimulates the penile growth. Although the pathogenesis of bilateral anorchia may be heterogeneous, our study suggests that gonads may have been functionally abnormal before they disappeared, and suggests that some patients have an intrinsic endocrine disorder.

Testicular torsion in Bristol: a 25-year review.

To identify changes in incidence, presentation, management and outcome, 670 patients with torsion of the spermatic cord presenting in Bristol between 1960 and 1984 have been reviewed. Among the susceptible population of 150,000, the annual incidence of torsion has increased fourfold from 11.2 cases between 1960 and 1964 to 42.8 cases between 1980 and 1984. Throughout this period greater than 90 per cent of patients have been managed by general surgeons. Patients aged between 12-18 years comprised 62 per cent but 20 per cent were 21 years or older. Torsion was commoner in the cold months, 24 per cent of cases occurring during December and January (chi 2 = 30.26, P less than 0.01). When acute torsion was relieved within 12 h of the onset of symptoms only 4 per cent of affected testes were considered non-viable, but beyond this time 75 per cent of patients received orchidectomy. Overall, 238 of 624 (38 per cent) acutely twisted testes were found to be infarcted at operation, and a further 35 patients (6 per cent) had marked testicular atrophy on review 3 months later. The testicular salvage rate has steadily improved from 45 per cent in the years 1960-64 to 67 per cent in 1980-84. Much of the increased incidence of testicular torsion is likely to reflect a greater awareness of the condition by general practitioners. It has been more than matched by an improvement in testicular salvage rate because of earlier referral.