Protective effect of rupatadine on testicular ischemia/reperfusion injury in rats: Modulation of IL-6/STAT3, Akt/ mTOR signaling pathways

• Published in: Toxicology and applied pharmacology Vol. 492; p. 117086
• Main Authors: Abdel-Aziz, Asmaa Mohamed, Abdelmonaem, Alyaa Abdelfattah, Thabit, Dina Moustafa, Marey, Heba, Ahmed, Sara M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2024
• Subjects: Apoptosis; Inflammatory Stress; Rupatadine; Testicular Ischemia/Reperfusion; Vascular Endothelial Growth Factor; Rupatadine; Vascular Endothelial Growth Factor; Inflammatory Stress; Testicular Ischemia/Reperfusion; Apoptosis
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2024.117086

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. 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. 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. 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. [Display omitted] •Testicular ischemia/reperfusion increased inflammation and cellular damage in rats•Rupatadine (RUP) has a platelet-activating factor receptor blocking activities.•RUP can improve the testicular levels of oxidative stress biomarkers.•RUP can modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways.•RUP improved testicular vasculature by increasing VEGF-A level which rescue testis.