{"title":"鲁帕他定对大鼠睾丸缺血再灌注损伤的保护作用：调节 IL-6/STAT3、Akt/ mTOR 信号通路","authors":"","doi":"10.1016/j.taap.2024.117086","DOIUrl":null,"url":null,"abstract":"<div><h3>Backgrounds & aim</h3><p>Spermatic cord rotation is a common problem in the field of urology, that finally results in necrosis of testicular tissue as well as male infertility. Rupatadine (RUP); a second-generation antihistaminic drug; demonstrated to have a possible protective effect in variable ischemia/reperfusion (I/R) rat models, but its role has not been studied yet in testicular I/R model.</p></div><div><h3>Material & methods</h3><p>The present study investigated RUP ability to ameliorate testicular I/R injury. The study includes four groups (6 rats/group); sham group, sham group pretreated with RUP (6 mg/kg/day; orally) for 14 days, I/R group, and RUP-I/R pretreated group.</p></div><div><h3>Key findings</h3><p>The results demonstrated that I/R significantly lowered serum testosterone level and testicular tissue content of reduced glutathione. Besides, a significant elevation in malondialdehyde level, hypoxia-inducible factor-1, signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), histamine, and platelet activating factor levels along with an inhibition in testicular tissue level of vascular endothelial growth factor-A (VEGF-A) with an evident increase in caspase-3 immunoexpression in germ cells. Also, I/R significantly lowered p-AKT and mTOR testicular expression. While, RUP-I/R pretreated group showed a reversal in the testicular I/R damaging effects in a significant manner in the all the aforementioned parameters.</p></div><div><h3>Conclusion</h3><p>Based on these findings; RUP was proved to have a possible protective effect in testicular I/R injury via its antioxidant effect and its ability to modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways with improvement in the testicular VEGF-A level.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective effect of rupatadine on testicular ischemia/reperfusion injury in rats: Modulation of IL-6/STAT3, Akt/ mTOR signaling pathways\",\"authors\":\"\",\"doi\":\"10.1016/j.taap.2024.117086\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Backgrounds & aim</h3><p>Spermatic cord rotation is a common problem in the field of urology, that finally results in necrosis of testicular tissue as well as male infertility. Rupatadine (RUP); a second-generation antihistaminic drug; demonstrated to have a possible protective effect in variable ischemia/reperfusion (I/R) rat models, but its role has not been studied yet in testicular I/R model.</p></div><div><h3>Material & methods</h3><p>The present study investigated RUP ability to ameliorate testicular I/R injury. The study includes four groups (6 rats/group); sham group, sham group pretreated with RUP (6 mg/kg/day; orally) for 14 days, I/R group, and RUP-I/R pretreated group.</p></div><div><h3>Key findings</h3><p>The results demonstrated that I/R significantly lowered serum testosterone level and testicular tissue content of reduced glutathione. Besides, a significant elevation in malondialdehyde level, hypoxia-inducible factor-1, signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), histamine, and platelet activating factor levels along with an inhibition in testicular tissue level of vascular endothelial growth factor-A (VEGF-A) with an evident increase in caspase-3 immunoexpression in germ cells. Also, I/R significantly lowered p-AKT and mTOR testicular expression. While, RUP-I/R pretreated group showed a reversal in the testicular I/R damaging effects in a significant manner in the all the aforementioned parameters.</p></div><div><h3>Conclusion</h3><p>Based on these findings; RUP was proved to have a possible protective effect in testicular I/R injury via its antioxidant effect and its ability to modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways with improvement in the testicular VEGF-A level.</p></div>\",\"PeriodicalId\":23174,\"journal\":{\"name\":\"Toxicology and applied pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology and applied pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041008X24002849\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24002849","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Protective effect of rupatadine on testicular ischemia/reperfusion injury in rats: Modulation of IL-6/STAT3, Akt/ mTOR signaling pathways
Backgrounds & aim
Spermatic cord rotation is a common problem in the field of urology, that finally results in necrosis of testicular tissue as well as male infertility. Rupatadine (RUP); a second-generation antihistaminic drug; demonstrated to have a possible protective effect in variable ischemia/reperfusion (I/R) rat models, but its role has not been studied yet in testicular I/R model.
Material & methods
The present study investigated RUP ability to ameliorate testicular I/R injury. The study includes four groups (6 rats/group); sham group, sham group pretreated with RUP (6 mg/kg/day; orally) for 14 days, I/R group, and RUP-I/R pretreated group.
Key findings
The results demonstrated that I/R significantly lowered serum testosterone level and testicular tissue content of reduced glutathione. Besides, a significant elevation in malondialdehyde level, hypoxia-inducible factor-1, signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), histamine, and platelet activating factor levels along with an inhibition in testicular tissue level of vascular endothelial growth factor-A (VEGF-A) with an evident increase in caspase-3 immunoexpression in germ cells. Also, I/R significantly lowered p-AKT and mTOR testicular expression. While, RUP-I/R pretreated group showed a reversal in the testicular I/R damaging effects in a significant manner in the all the aforementioned parameters.
Conclusion
Based on these findings; RUP was proved to have a possible protective effect in testicular I/R injury via its antioxidant effect and its ability to modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways with improvement in the testicular VEGF-A level.
期刊介绍：
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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