Use of alpha lipoic acid in preventing drug-induced cell damage in rat testicular tissue

This study aimed to evaluate the protective effects of alpha-lipoic acid (ALA), a potent antioxidant, on testicular oxidative damage induced by acitretin (ACT) and methotrexate (MTX) in rats, focusing specifically on the activities of cytosolic superoxide dismutase (SOD) and mitochondrial Mn-superoxide dismutase (MnSOD). Wistar albino rats were divided into four groups: control, ALA-only, ACT+MTX, and ACT+MTX+ALA. ACT (20 mg/kg/day), MTX (20 mg/kg/week), and ALA (50 mg/kg/day) were administered intraperitoneally. Rats were sacrificed on days 3, 5, and 7 post-treatment. SOD and MnSOD activities in testicular tissue were analyzed spectrophotometrically. Non-parametric Kruskal-Wallis tests were applied due to the non-normal distribution of data. The ACT+MTX group showed significant increases in both SOD and MnSOD activities, indicating strong oxidative stress induction. While ALA alone led to a non-significant, time-dependent increase in enzyme activities, its co-administration with ACT+MTX moderately reduced the oxidative stress response but failed to achieve statistical significance. The suppressive effect of ALA was more evident on mitochondrial MnSOD activity than cytosolic SOD, suggesting limited but tissue-specific antioxidant activity. The combination of ACT and MTX induces considerable oxidative stress in rat testicular tissue. ALA administration demonstrated a trend toward protective effects, particularly at the mitochondrial level, though not statistically significant. The findings suggest that ALA may offer partial cytoprotection, and further studies with adjusted dosing, extended durations, and broader antioxidant profiling are necessary to clarify its therapeutic potential in drug-induced reproductive toxicity.