Amaranthus viridis Ameliorates Oxidative Stress and Modulates TNF-β in Tramadol- Induced Testicular Toxicity

Background: Tramadol, a synthetic opioid analgesic, is associated with reproductive toxicity and testicular oxidative damage following prolonged exposure. Amaranthus viridis (green amaranth), a medicinally valued tropical vegetable, possesses antioxidant and anti-inflammatory properties that may offer protective effects. This study investigated the protective potential of Amaranthus viridis leaf extract against tramadol-induced testicular toxicity in adult male Wistar rats, focusing on oxidative stress biomarkers, reproductive hormones, and inflammatory cytokines. Method: Twenty-five adult male Wistar rats were randomly assigned into five groups (n=5). Group 1 received distilled water (control); Group 2 received 200 mg/kg tramadol (toxic control); Groups 3, 4, and 5 were administered combined doses of tramadol (150, 100, and 50 mg/kg, respectively) and Amaranthus viridis extract (100, 200, and 300 mg/kg, respectively) for 21 days via oral gavage. Testicular tissues and serum samples were evaluated for histology, oxidative stress markers (SOD, GPx, MDA), reproductive hormones (LH, FSH, testosterone), and inflammatory cytokines (IL-1, IL-6, TNF-α, TNF-β). Results: Tramadol administration significantly disrupted testicular histoarchitecture and caused a marked reduction in LH, FSH, testosterone, SOD, and GPx levels, along with elevated MDA and TNF-β levels (p<0.05). Co-treatment with A. viridis extract, especially at 300 mg/kg, significantly restored LH, FSH, testosterone, SOD, and GPx levels and suppressed TNF-β expression, although MDA levels remained elevated. Histologically, A. viridis treatment attenuated germ cell necrosis and improved seminiferous tubule integrity. Conclusion: A. viridis extract demonstrated a dose-dependent protective effect against tramadol-induced testicular toxicity by enhancing antioxidant defenses, restoring hormonal balance, and suppressing proinflammatory cytokines-highlighting its therapeutic potential in male reproductive health.