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

Autor: Abdel-Aziz AM; Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt. Electronic address: asmaaabdelaziz303@yahoo.com., Abdelmonaem AA; Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt., Thabit DM; Department of pathology, Faculty of Medicine, Minia University, 61511 Minia, Egypt., Marey H; Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt., Ahmed SM; Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Sep 06; Vol. 492, pp. 117086. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1016/j.taap.2024.117086
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Asmaa Abdel-Aziz reports a relationship with Minia University Faculty of Medicine that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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