Protective effects of rutin against docetaxel-induced testicular damage in rats: Effects on antioxidant defence, apoptosis and autophagy

Docetaxel (DTX), a widely used chemotherapeutic agent, is known for its effectiveness in Cancer treatment but also for its toxic effects on healthy tissues, particularly the male reproductive system. This study aimed to investigate the protective role of rutin, a natural flavonoid with known antioxidant and anti-apoptotic properties, against DTX-induced testicular damage in rats. Thirty-six adult male Wistar rats were randomly divided into six groups: Control, Rutin 50 mg/kg (R50), Rutin 100 mg/kg (R100), DTX, DTX+R50, and DTX+R100. A single dose of DTX (30 mg/kg, i.p.) was administered, while rutin was given orally for 7 days. On day eight, all Animals were sacrificed. Sperm parameters (concentration, motility, morphology, chromatin integrity), serum testosterone and Inhibin B levels, and testicular MDA and SOD levels were assessed. Histological evaluations were conducted using hematoxylin-eosin staining, Johnsen scoring, and tubule diameter measurements. Immunohistochemical analysis of Caspase-3, Bax, Bcl-2, mTOR, ULK1, and Atg13 was performed. Data were analyzed, and p < 0.05 was considered statistically significant. DTX significantly impaired sperm motility and hormone levels, increased oxidative stress, and caused histological damage in the testes (p < 0.001). Rutin, especially at 100 mg/kg, ameliorated these effects, restoring sperm function, hormonal balance, and testicular architecture. Furthermore, rutin reduced DTX-induced Apoptosis and Autophagy marker expression while preserving Bcl-2 levels (p < 0.001). DTX induces structural and functional impairments in testicular tissue via oxidative stress, Apoptosis, and Autophagy. Rutin demonstrated a dose-dependent protective effect, suggesting its potential as a supportive agent against chemotherapy-induced gonadotoxicity.

Apoptosis; Autophagy; Docetaxel; Oxidative stress; Rutin; Testicular toxicity.