Trolox is more successful than allopurinol to reduce degenerative effects of testicular ischemia/reperfusion injury in rats (original) (raw)
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Medical perspective in testicular ischemia‑reperfusion injury (Review)
Experimental and Therapeutic Medicine, 2017
Testicular torsion or torsion of the spermatic cord is one of the most serious urological conditions. It causes testicular injury, which potentially leads to male subfertility. The turning of the spermatic cord and spermatic structures around themselves results in biochemical and histological changes; however, following testicular detorsion, tissues undergo reperfusion that causes more severe damage than that induced by ischemia. Since the primary causes of testicular damage are reactive oxygen species production, an increase in intra-mitochondrial calcium concentration and an increased rate of cellular apoptosis, different medications may potentially be effective. It seems that several medications, experimentally and sometimes clinically, serve an adjuvant role in the cellular damage that occurs following ischemia-reperfusion. Antioxidants, calcium channel blockers, phytotherapeutical medicinals, anaesthetics, hormones and platelet inhibitors may potentially create a solid basis for an adjuvant restoring therapy and ameliorate testicular function following torsion. The current study aimed to review the relevant literature and discuss the actions of a number of molecules that may protect the testes during ischemia/reperfusion injury.
Medical perspective in testicular ischemia-reperfusion injury
Experimental and Therapeutic Medicine, 2017
Testicular torsion or torsion of the spermatic cord is one of the most serious urological conditions. It causes testicular injury, which potentially leads to male subfertility. The turning of the spermatic cord and spermatic structures around themselves results in biochemical and histological changes; however, following testicular detorsion, tissues undergo reperfusion that causes more severe damage than that induced by ischemia. Since the primary causes of testicular damage are reactive oxygen species production, an increase in intra-mitochondrial calcium concentration and an increased rate of cellular apoptosis, different medications may potentially be effective. It seems that several medications, experimentally and sometimes clinically, serve an adjuvant role in the cellular damage that occurs following ischemia-reperfusion. Antioxidants, calcium channel blockers, phytotherapeutical medicinals, anaesthetics, hormones and platelet inhibitors may potentially create a solid basis for an adjuvant restoring therapy and ameliorate testicular function following torsion. The current study aimed to review the relevant literature and discuss the actions of a number of molecules that may protect the testes during ischemia/reperfusion injury.
The Journal of Urology, 2008
Recent evidence suggests that enhanced cell apoptosis is responsible for germ cell loss following testicular ischemia-reperfusion (IR) injury. A nonsteroidal anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis inhibitor, which is widely used in many testicular disorders. The purpose of the present study was to examine the effect of diclofenac (DIC) on germ cell apoptosis in the ischemic and contralateral testes following testicular IR in a rat. Forty rats were divided randomly into four experimental groups of ten rats each: group A (Sham)-Sham operated animals; group B (Sham-DIC)-Sham operated rats that were treated with DIC given subcutaneously at a dose of 10 mg/kg, once daily, 24, 48 and 72 h following operation; group C (IR) underwent 90 min of unilateral testicular IR; group D (IR-DIC)-rats underwent 90 min of unilateral testicular IR and were treated with DIC similarly to group B. Ninety-six hours following operation, the rats were sacrificed and testes were harvested. Johnsen's criteria and the number of germinal cell layers were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in both the ischemic and contralateral testes. Statistical analysis was performed using the nonparametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Testicular ischemia in rats led to histological damage in the ipsilateral testis. In the contralateral testis, minimal damage was observed. Germ cell apoptosis in both the ischemic and the contralateral testes increased significantly after IR. Treatment with DIC did not change histologic parameters of spermatogenesis in both the ischemic and contralateral testes, but decreased germ cell apoptosis in both testes following testicular IR. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. Diclofenac may be beneficial for spermatogenesis following testicular IR by decreasing germ cell apoptosis.
Pioglitazone Eases Testicular Torsion/Detorsion-Induced Ischemia- Reperfusion Injury in Rats
Journal of Urological Surgery, 2023
Objective: This study demonstrated the protective effects of pioglitazone (Pio) on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury. Materials and Methods: A total of 48 male rats were randomly divided into six experimental groups of eight rats each; Control group, I/R group, Pio 3 mg/kg group, I/R treated with Pio 3 mg/kg group, Pio 6 mg/kg group, and I/R treated with Pio 6 mg/kg group. Testicular torsion was induced by twisting the left testis 720 °C in a clockwise direction (I/R groups). Both ischemia and reperfusion periods were 4 h. Single-dose 3 mg/kg Pio or 6 mg/kg Pio was administered orally two hours before reperfusion (Pio groups). Left orchiectomy was performed at the end of the protocol. Results: In the I/R within-group analysis for mean seminiferous tubule diameter and epithelial lengths, a statistically significant difference was found only in the Pio 6 group (p=0.005; p=0.005). But Pio treatment failed to improve the levels of malondialdehyde and glutathione. Also, it did not cause any change in the non-I/R groups. Conclusion: Considering the findings of Pio, it may be used in emergencies such as torsion and other chronic diseases.
The Eurasian Journal of Medicine, 2020
Aims and Scope Eurasian Journal of Medicine (Eurasian J Med) is an international, scientific, open access periodical published by independent, unbiased, and triple-blinded peer-review principles. The journal is the official publication of Atatürk University School of Medicine and published triannually in February, June, and October. The publication language of the journal is English. The aim of the Eurasian Journal of Medicine is to publish original research papers of the highest scientific and clinical value in all medical fields. The Eurasian J Med also includes reviews, editorial short notes and letters to the editor that either as a comment related to recently published articles in our journal or as a case report. The target audience of the journal includes researchers, physicians and healthcare professionals who are interested or working in in all medical disciplines.
The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats
Pediatric Surgery International, 2007
This study was designed to investigate the protective effect of trimetazidine [TMZ; 1-(2, 3, 4-trimeth hoxibenzyl)-piperazine dihydrochloride], as an antioxidant agent, on torsion-detorsion-induced biochemical and histopathological changes in experimental testicular ischemia/ reperfusion injury in rats. Twenty-seven male Wistar rats weighing 180-220 g were divided into five groups: control (C, n = 4), sham-operated (S, n = 4), ischemia (I, n = 6), ischemia-reperfusion (I/R, n = 6) and ischemia-reperfusion + trimetazidine (I/R + TMZ; n = 7). Control rats were used for basal normal values. In group I, 2 h torsion of the left testis was performed. In I/R and I/R + TMZ groups, following 2 h of torsion, 4 h detorsion of the testis was performed. In ischemia and I/R groups, physiologic saline was administered orally for 7 days, and the rats in I/R + TMZ group were pretreated orally with 5 mg/kg day TMZ for 7 days before inducing ischemia. At the end of each experiment, ipsilateral orchiectomies were performed for the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GPx) enzyme activities and histopathological examinations in all groups. MDA levels were significantly reduced and GPx enzyme activities were significantly increased in testes in I/R+TMZ pretreated group compared to group I and I/R. The mean seminiferous tubular diameter (MSTD) and Johnsen's score were significantly better in I/R+TMZ group than groups I and I/R. Pretreatment with TMZ decreased germ cell apoptosis and caspase-3 expression in the ischemic testis.
Journal of Pediatric Surgery, 2012
Aim: Even with prompt diagnosis and treatment, testicular torsion may lead to infertility and atrophy after testicular salvage. The aims of this study were to investigate the long-term protective effects of short-interval postconditioning on testicular atrophy and to optimize the reperfusion period. Materials and Methods: Forty adult male rats were divided into 5 subgroups: sham operated; torsion + detorsion; torsion + postconditioning, 5 seconds (PC5); torsion + postconditioning, 10 seconds; and torsion + postconditioning, 20 seconds. Torsion was created by rotating the left testis 1080°c ounterclockwise and then fixing the testis to the scrotum with 3 sutures. Torsion was maintained for 4 hours. The testicular artery was visualized, and an atraumatic vascular clamp was applied to prevent reperfusion in all study groups. Detorsion of the testis was then performed. In the torsion + detorsion group, the clamp was released just after detorsion. In all the other intervention groups, the subsequent procedures were repeated 10 times. In the PC5 group, the clamp was released for 5 seconds and applied for 10 seconds; in the torsion + postconditioning, 10 seconds group, the clamp was released for 10 seconds and applied for 10 seconds; and in the torsion + postconditioning, 20 seconds group, the clamp was released for 20 seconds and applied for 10 seconds. Then, reperfusion was allowed. After 60 days, rats in all study groups were killed, both testes were removed, and the histopathology was evaluated. The χ 2 test was used for statistical analysis. Results: Compared with the other groups, the extent of tissue injury determined by histopathologic grades according to Cosentino et al (J Androl. 1986;7:23-31) was significantly less in group PC5 (P b .05). Conclusion: We conclude that short-interval postconditioning can protect against long-term testicular reperfusion injury. Furthermore, the optimal time for reperfusion during postconditioning was 5 seconds in our rat model of testicular torsion. This technique seems easily applicable, and evidence suggests that similar techniques may be useful during testicular surgery.
Journal of Pediatric Surgery, 2011
Aim: Testicular torsion can lead to testicular damage. During reperfusion, tissue damage is more severe. The aim of this study was to investigate the protective effect of short-interval postconditioning and determine the optimal time of reperfusion for postconditioning. Materials and Methods: Thirty-five adult male rats were divided into 5 subgroups: Sh (sham operated), TD (torsion + detorsion), PC5 (torsion + postconditioning 5 seconds), PC10 (torsion + postconditioning-10 seconds), PC20 (torsion + postconditioning 20 seconds). Torsion was created by rotating the left testis counterclockwise 1080°and the testis fixed to the scrotum with 3 sutures. Torsion was maintained for 4 hours. The testicular artery was visualized, and before detorsion of the testis, an atraumatic vessel clamp was applied to prevent reperfusion in all study groups. Then, detorsion of the testis was performed. In the TD group, the clamp was released just after detorsion; in the PC5 group, the clamp was released for 5 seconds and closed for 10 seconds (10 times); in the PC10 group, the clamp was released for 10 seconds and closed for 10 seconds (10 times); and in the PC20 group, the clamp was released for 20 seconds and closed for 10 seconds (10 times). Then, all testes were reperfused for a 1hour period in all study groups. After this period, the rats were sacrificed, and the left testes were removed and evaluated histopathologically and biochemically. The Mann-Whitney U test was used for statistical analyses. Results: Tissue malondialdehyde levels were 79.3 ± 10.6, 231.7 ± 102.3, 71.3 ± 12.6, 73.8 ± 13.7, and 124.3 ± 48.0 nmol/g tissue in the Sh, TD, PC5, PC10, and PC20 groups, respectively. Tissue malondialdehyde levels were significantly lower in the PC5 and PC10 groups (P b .05) compared to the other groups. However, mean histopathologic grade was lower in all postconditioning groups compared to the control group, but the difference was significant only in the PC5 group (P b .05). Conclusion: We conclude that short-interval postconditioning can reduce reperfusion injury in ischemic tissue and the optimal mode of short-interval postconditioning is 5 seconds × 10 times. This technique seems easily applicable, and a similar technique may be used during testicular surgery.
Vardenafil Reduces Testicular Damage Following Ischemia/Reperfusion Injury in Rats
The Kaohsiung Journal of Medical Sciences, 2009
Testicular torsion is a pathologic condition that renders the testis ischemic, and surgical intervention is usually required to re-establish blood flow [1]. Although the basic pathological mechanism underlying testicular injury is not completely understood, it has been shown that reactive oxygen species (ROS), formed during ischemia/reperfusion (I/R), play an important role in this process [2,3]. Identification of pharmacologic agents, administered as an adjunctive therapy to surgical repair for rescuing the testis from I/R injury, is a clinically important goal [4-6]. Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, tadalafil and vardenafil, are a new class of vasoactive drugs that have been developed for the treatment of erectile dysfunction [7,8]. The expression of PDE5 in vascular smooth muscle and in platelets has been demonstrated [9]. Several studies have been published recently and indicate that vardenafil may exert a powerful cardioprotective effect against I/R
Protective effect of osthole on testicular ischemia/reperfusion injury in rats
Turkish journal of trauma & emergency surgery, 2022
BACKGROUND: Testicular torsion is a urological emergency that requires urgent surgical intervention which results in testicular loss if not diagnosed and treated in a timely fashion. Ischemic tissue damage with oxygen deficiency, which starts with the decrease in blood flow to the tissue, continues to increase with the reoxygenation of the damaged tissues as soon as reperfusion is achieved. In various studies, osthole has also been shown to reduce cerebral, spinal cord, intestinal, renal, and myocardial ischemia/perfusion (I/R) damage. The aim of this study is to examine the effects of osthole on testicular I/R injury. METHODS: 28 Wistar-albino rats were randomly divided into four experimental groups (n=7). Group 1 was the sham operation group. In Group 2 (I/R), 3-h ischemia was created by rotating the testis 720° clockwise, followed by 3 h of reperfusion. In Group 3 (I/R + single dose of Osthole), 20 mg/kg ostol was administered intraperitoneally half an hour before detorsion after 3 h of torsion. The testis was detorsioned. Three h of detorsion was applied. In Group 4 (I/R + twice doses of Osthole), 20 mg/kg ostol was administered intraperitoneally half an hour before detorsion, followed by 3-h torsion. The testis was released and detorsioned. Half an hour after the detorsion, an intraperitoneal dose of 20 mg/kg osthole was administered again. Detorsion was done for 3 h. All rats were sacrificed after 6 h and right orchiectomy was performed for blood for biochemical analysis and histopathological sample. RESULTS: Glutathion, nuclear respiratory factor 2, Superoxide dismutase, and 8-hydroxydeoxyguanosine levels were decreased in I/R rats, while interleukin-6, malondialdehyde, and myeloperoxidase levels were increased. While caspase 3, caspase 8, caspase 9, and TUNEL showed moderate immunopositive tissues immunohistochemically in rats with I/R damage, mild immunopositive tissues were detected in Group 3 and Group 4. In the histochemical examination, degenerative tubule structure and separation of epithelial cells were observed in I/R rats, while partially healed testicular tissue was detected in Group 3 and Group 4. CONCLUSION: In our study, we observed that osthole reduced oxidative damage, suppressed the inflammatory process, prevented apoptosis, and reduced cell damage. We think that with repeated doses, cellular damage would gradually decline.