Idebenone regulates sirt1/Nrf2/TNF-α pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats. (10th May 2022)

• Record Type: Journal Article
• Authors: Abdelzaher, Walaa Yehia; Mostafa-Hedeab, Gomaa; Sayed AboBakr Ali, Abdel Hamid; Fawzy, Michael Atef; Ahmed, Amira F; Bahaa El-deen, Mohamed Ahmed; Welson, Nermeen N; Aly Labib, Dina A
• Is Part Of: Human & experimental toxicology. Volume 41(2022)
• Publication Date: 2022-05-10
• Subjects: idebenone -- juvenile rat -- testicular torsion/detorsion -- sirt1 -- Nrf2 -- TNF-α; Toxicology -- Periodicals; 615.9
• DOI: 10.1177/09603271221102515
• Languages: English
• ISSNs: 0960-3271

Abstract

Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i. p) without T/D; (3) the T/D group: rats underwent torsion for 2 h and detorsion for 4 h; and (4) the IDE+ T/D group: rats received IDE 1 h before T/D. Testicular malondialdehyde (MDA), total nitrite/nitrate (NOx), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), caspase-3, sirtuin type 1 (Sirt1), serum interleukin-1β (IL-1β), total cholesterol, and testosterone were measured. Histological changes, nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2), and proliferating cell nuclear antigen (PCNA) immuno-expressions were assessed. T/D displayed an increase in MDA, NOx, TNF-α, caspase-3, IL-1β, and total cholesterol with a significant decrease in TAC, Sirt1, and testosterone and strong positive Nrf2 and negative PCNA immuno-expressions. IDE could improve all oxidative, inflammatory, and apoptotic indicators. Therefore, IDE significantly reduced testicular ischemia-reperfusion injury in the juvenile rat testicular T/D model by limiting oxidative stress, inflammation, and apoptosis via the Sirt1/Nrf2/TNF-α pathway. Graphical Abstract