Protective Effects of Topical Application of Nitrite on Testicular Ischemia-Reperfusion Injury in Rats

Testicular torsion is a urologic emergency induced by torsion of the spermatic cord, interrupting blood circulation to the testis. Therapeutic options for testicular torsion, except surgical restoration of testis, are rarely applied in clinical practice. This study, therefore, investigated whether topical application of nitrite (NO2-) is beneficial in tissue damage due to testicular ischemia-reperfusion (I/R) injury in rats. Pubertal Sprague-Dawley rats were assigned to seven groups: group A, sham-operated control group; group B, I/R with no treatment; groups C, D, and E, I/R followed by treatment with three different doses of nitrite; group F, I/R followed by administration of nitrite and a NO scavenger, C-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt); and group G, I/R followed by administration of nitrate (NO3-). Unilateral testicular ischemia was maintained for 5 h, followed by reperfusion for 24 h. Nitrite and nitrate were topically administered before reperfusion. Compared to group A, germ cell apoptosis, oxidative stress, antioxidant enzymatic function, and lipid peroxidation were significantly increased, along with abnormal morphology and impaired spermatogenesis in group B ( P < 0.05 ). In contrast, testicular damage was generally attenuated in the nitrite treatment groups due to a reduction in superoxide and peroxynitrite levels and the inhibition of caspase-3-dependent apoptosis ( P < 0.05 vs. group B). These therapeutic effects of nitrite-derived NO were suppressed after injection of C-PTIO, which showed in group F. Taken together, our results demonstrate that topical application of nitrite may be one of the therapeutic strategies for testicular ischemia-reperfusion injury.

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The long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

10.21203/rs.3.rs-79465/v1 ◽

2020 ◽

Author(s):

Bomi Kim ◽

EunHye Lee ◽

BoHyun Yoon ◽

So Young Chun ◽

Jae-Wook Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Reperfusion Injury ◽

Rat Model ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Group A ◽

Testicular Ischemia

Abstract Background Testicular torsion is a urological emergency in which misdiagnosis and inappropriate treatment can lead to testicular atrophy and male infertility owing to ischemia-reperfusion injury (IRI). Although experimental studies of testicular torsion have been preceded, promising therapeutic agents based on the long-term effect for spermatogenesis have not been identified in testicular ischemia reperfusion injury (IRI) animal model. Tadalafil, one of the phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against IRI in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model. Methods Forty-eight adolescent Sprague–Dawley rats were divided into 6 groups (A-F). Sham operation was performed in group A. Group B received surgical 720-degree torsion of the left testis without any medication. Groups C, D, E, and F were operated surgical torsion with tadalafil at varying doses (0.3 mg/kg, 1.0 mg/kg) and durations (single or daily administration for 4 weeks). Detorsion was performed after 3 hour of torsion in all rats except the sham group. Four weeks after operation, both testes were evaluated of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C. Results For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts. The groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration. Furthermore, molecular markers (MDA and SOD) related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration. Conclusion Tadalafil alleviated long-term deterioration of spermatogenesis and oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.

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Protective Effect of BMSCs-derived Exosomes on Testicular Ischemia-reperfusion Injury in Rats

10.21203/rs.3.rs-184044/v1 ◽

2021 ◽

Author(s):

Hu Tian ◽

Wan-song Zhang ◽

Cheng Yang ◽

Jun-hao Zhou ◽

Ran-ran Zhou ◽

...

Keyword(s):

Treatment Group ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Testicular Tissue ◽

Sd Rats ◽

Group I ◽

Group A ◽

Testicular Ischemia ◽

Group B

Abstract Background: Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.Methods: BMSCs were isolated, cultured and identified by primary culture method. Exosomes derived from BMSCs were extracted by ultra-high speed centrifugation method. A testicular IRI model was established in male SD rats. Thirty healthy male SD rats were randomly divided into three groups. Group A: Sham group, group B: normal saline treatment group (I/R+NS), group C: BMSCs-derived exosomes (100 ug/mL) treatment group (I/R+ BMSCs-EXO). Finally take each side (left) of rat torsion by using optical microscope to detect testicular tissue pathology grade and fine structure of organization structure, adopt the method of biochemical determination of groups of testicular tissue MDA and NOS, SOD and CAT activity and T - AOC level.Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In animal model, Compared with the normal spermatogenic structure of testis in group A (Sham), the spermatogenic structure of testis in group B (I/R+NS) was obviously damaged to varying degrees, while the spermatogenic structure of testis in group C (I/R+ BMSCs-EXO) was improved to A certain extent (P<0.05). In the biochemical indexes of testis tissue, the contents of MDA and NOS in group B (I/R+NS) were significantly increased compared with group A (Sham), while the activities of SOD and CAT and T-AOC were decreased compared with group A (Sham) (P<0.05). In the exosome-treated group C (I/R+ BMSCs-EXO), compared with the normal saline treatment group B, The contents of MDA and NOS were decreased to a certain extent, while the activities of SOD and CAT and the level of T-AOC were increased (P<0.05).Conclusion: BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

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The Protective Effects of Fasciotomy on Reperfusion Injury of Skeletal Muscle of Rabbits

BioMed Research International ◽

10.1155/2017/7238960 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Rui-Hua Li ◽

Jin Li ◽

Shi-Lian Kan ◽

Xi-Nan Zhang

Keyword(s):

Skeletal Muscle ◽

Reperfusion Injury ◽

Treatment Effects ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Healthy Male ◽

Group A ◽

Group B ◽

Better Than

The authors aim to investigate protective effects of fasciotomy against ischemia reperfusion injury of skeletal muscle in rabbit and to compare the treatment effects of prereperfusion + fasciotomy and fasciotomy + postreperfusion against ischemia reperfusion injury of skeletal muscle. 24 healthy male Japanese white rabbits were randomly divided into 3 groups, and 4 hours’ ischemia was established in these rabbits through surgery. Six hours’ reperfusion was performed in group A; reperfusion + postfasciotomy was performed in group B; and prefasciotomy + reperfusion was performed in group C. Result showed that prefasciotomy and postfasciotomy could protect skeletal muscle against ischemia reperfusion injury, reduced MDA (malondialdehyde) expression, MPO (myeloperoxidase) expression, and apoptosis of muscle in the reperfused areas, increased Bcl-2 expression, and decreased Bax expression. The MDA and MPO levels in group B and group C were significantly lower than those in group A, and MDA and MPO levels in group C were significantly lower than those in group B. Prefasciotomy and postfasciotomy could protect against ischemia reperfusion injury in skeletal muscle. The protective effects of prefasciotomy against ischemia reperfusion injury are better than postfasciotomy.

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Effects of melatonin on spermatogenesis and testicular ischemia-reperfusion injury after unilateral testicular torsion-detorsion

Journal of Pediatric Surgery ◽

10.1016/j.jpedsurg.2008.01.065 ◽

2008 ◽

Vol 43 (10) ◽

pp. 1873-1878 ◽

Cited By ~ 28

Author(s):

Müslim Yurtçu ◽

Adnan Abasiyanik ◽

Mustafa Cihat Avunduk ◽

Sabahattin Muhtaroğlu

Keyword(s):

Reperfusion Injury ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Testicular Ischemia

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Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial

AJP Renal Physiology ◽

10.1152/ajprenal.00340.2015 ◽

2016 ◽

Vol 311 (3) ◽

pp. F567-F575 ◽

Cited By ~ 6

Author(s):

Saskia J. H. Brinkmann ◽

Nikki Buijs ◽

Mechteld A. R. Vermeulen ◽

Efraim Oosterink ◽

Henk Schierbeek ◽

...

Keyword(s):

Clinical Trial ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Aortic Surgery ◽

Glutamine Supplementation ◽

Abdominal Aortic Surgery ◽

Abdominal Aortic ◽

Group A ◽

Group B

Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg−1·day−1; group A, n = 5) or no supplement ( group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg−1·h−1, citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg−1·h−1, and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg−1·h−1, P < 0.01), as was the synthesis of citrulline from glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg−1·h−1), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg−1·h−1), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg−1·h−1), respectively ( P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

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Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREMτ Expression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9043806 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Si-Ming Wei ◽

Rong-Yun Wang ◽

Yan-Song Chen

Keyword(s):

Reactive Oxygen Species ◽

Reperfusion Injury ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Control Group ◽

Oxygen Species ◽

Germ Cell Differentiation ◽

Testicular Ischemia

Testicular torsion/detorsion-induced damage is considered as a typical ischemia-reperfusion injury attributed to excessive reactive oxygen species (ROS) production. ROS may regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The cAMP-responsive element modulator-τ (CREMτ) gene expression in the testis is essential for normal germ cell differentiation. The present study was aimed at investigating the effect of sesamol, a powerful antioxidant, on testicular ischemia-reperfusion injury and related mechanisms in an experimental testicular torsion-detorsion rat model. The type of our study was a randomized controlled trial. Sixty rats were randomly divided into the following 3 groups: (1) sham-operated control group (n=20), (2) testicular ischemia-reperfusion group (n=20), and (3) testicular ischemia-reperfusion+sesamol-treated group (n=20). Testicular ischemia-reperfusion was induced by left testicular torsion (720° rotation in a counterclockwise direction) for 2 hours, followed by detorsion. Orchiectomy was performed at 4 hours or 3 months after detorsion. The testis was obtained for the analysis of the following parameters, including malondialdehyde level (a sensitive indicator of ROS), CREMτ expression, and spermatogenesis. In the testicular ischemia-reperfusion group, the malondialdehyde level was significantly increased with a concomitant significant decrease in CREMτ expression and spermatogenesis in ipsilateral testis. These results suggest that overproduction of ROS after testicular ischemia-reperfusion may downregulate CREMτ expression, which causes spermatogenic injury. Sesamol treatment resulted in a significant reduction in the malondialdehyde level and significant increase in CREMτ expression and spermatogenesis in ipsilateral testis. These data support the above suggestion. Our study shows that sesamol can attenuate testicular ischemia-reperfusion injury through scavenging ROS and upregulating CREMτ expression.

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PO-032 The protective effects of curcumin on exercise-induced renal ischemia reperfusion injury in rats

Exercise Biochemistry Review ◽

10.14428/ebr.v1i3.9973 ◽

2018 ◽

Vol 1 (3) ◽

Author(s):

Fang Li ◽

Jianmin Cao ◽

Haitao Zhou ◽

Yanlong Niu

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Inflammatory Factors ◽

Control Group ◽

Renal Ischemia Reperfusion Injury ◽

Group A ◽

Exercise Induced ◽

Group B

Objective This study was designed to investigate the effects of curcumin on inflammatory factors and ECM expression in exercise-induced renal ischemia reperfusion injury in rats. Methods Sixty 7-week-old male SD rats were divided randomly into three groups: group A (normal control group, n=12), group B (overtraining group, n=24) and group C (curcumin + overtraining group, n=24). Group B and C performed 6 weeks of incremental load training on the treadmill. 24 hours after the last training, the rats were anesthetized intraperitoneally, the morphology of renal tissue and the deposition of glomerular ECM were observed using light microscope，the related biochemical indexes were tested. Results (1) the renal structure of rats in group A were normal, histopathological changes were observed in group B and C, Paller score of group B were significantly higher than group A(P <0.01), and that of group C were significantly lower than group B(P <0.05). (2) Blood urea nitrogen (BUN) and serum creatinine (Scr), serum and renal inflammatory factors , TGF-β protein expression level and glomerular ECM deposition of group B were significantly higher than group A(P<0.01) and those of group C were lower than group B(P<0.05). Conclusions Supplementation of curcumin can effectively protect rats from exercise-induced renal ischemia reperfusion injury, by inhibiting the up-regulation of inflammatory cytokines and TGF-β expression and maintaining the dynamic balance of ECM .

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Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

10.21203/rs.3.rs-184044/v3 ◽

2021 ◽

Author(s):

Hu Tian ◽

Wan-song Zhang ◽

Cheng Yang ◽

Jun-hao Zhou ◽

Ran-ran Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Stem Cell ◽

Treatment Group ◽

Mesenchymal Stem Cell ◽

Reperfusion Injury ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Testicular Ischemia

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Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

10.21203/rs.3.rs-184044/v2 ◽

2021 ◽

Author(s):

Hu Tian ◽

Wan-song Zhang ◽

Cheng Yang ◽

Jun-hao Zhou ◽

Ran-ran Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Stem Cell ◽

Treatment Group ◽

Mesenchymal Stem Cell ◽

Reperfusion Injury ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Testicular Ischemia

Abstract Background Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury. Methods Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group. Conclusion BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

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