Alcohol induces testicular dysfunction through altered prostaglandins E2 & F2A, COX-1, expression and DNA oxidation: The role of glutathione

Ethanol is a known gonadotoxin causing testicular oxidative stress, inflammation, and DNA damage that impairs steroidogenesis and sperm production, leading to male subfertility. We evaluated whether D-ribose-L-cysteine (Drlc), a glutathione precursor, protects against ethanol-induced testicular injury. Adult male Wistar rats (n = 20) weighing 190–210 g were randomly assigned to control (3 ml/kg body weight of distilled water), alcohol (3 g/kg, 40% v/v), Drlc (52 mg/kg), or ethanol + Drlc groups. Following euthanasia, blood and the testis were used to measure serum/testicular testosterone and estradiol, testicular antioxidants (GSH, SOD, CAT) and lipid peroxidation (MDA); pro-inflammatory cytokines (TNF-α, IL-1β); prostaglandins (PGE₂, PGF₂α) and COX-1; sperm DNA oxidation (8-OHdG); and epididymal sperm count, motility, viability, and morphology. Ethanol consumption markedly disrupted testicular physiology: intratesticular testosterone fell while estradiol rose. Antioxidant defenses (glutathione, SOD, and CAT) were depleted, and lipid peroxidation (MDA) increased. Pro-inflammatory cytokines (TNF-α, IL-1β) were elevated. Ethanol also upregulated testicular prostaglandins E₂ and F₂α and COX-1, increased sperm DNA oxidation (8-OHdG), and impaired epididymal sperm count, motility, viability, and normal morphology. Co-administration of Drlc significantly prevented these effects by restoring glutathione and antioxidant enzyme levels, reducing MDA, normalizing cytokine and prostaglandin levels, diminishing DNA oxidation, and preserving sperm count and motility relative to ethanol alone. These findings highlight oxidative stress, inflammation, prostaglandin dysregulation, and DNA damage as central to alcohol-induced testicular injury. Glutathione augmentation with Drlc preserved steroidogenesis and sperm quality, underscoring the potential of antioxidant strategies to mitigate toxicant effects and protect male fertility.