Abstract
OBJECTIVE: This study aimed to compare the comparative protective effects of Melatonin (Mel) and Glutathione (GSH) against Carboplatin (CARB)-induced ovarian toxicity in rats, with a focus on folliculogenesis, oxidative stress, inflammation, and apoptosis. METHODS: Female Wistar rats were allocated into six groups: Control, GSH, Mel, CARB, GSH+CARB, and Mel+CARB. Mel and GSH were administered intraperitoneally for 7 days before CARB injection. Ovarian tissues were subjected to histopathological and morphometric analyses, while serum oxidative stress markers (MDA, SOD, CAT, GSH-Px), proinflammatory cytokines (TNF-α, IL-6), and AMH levels were quantified. Caspase-3 and NF-κB expressions were evaluated immunohistochemically. RESULTS: CARB caused severe ovarian injury characterized by marked follicular depletion, stromal edema, hemorrhage, inflammation, fibrosis, and a significant reduction in preantral and Graafian follicles, with a concomitant increase in atretic follicles (p < 0.01). Both Mel and GSH pre-treatment markedly reduced histological damage, restored follicular counts, improved antioxidant status, and suppressed inflammatory and apoptotic responses. Melatonin tended to exert stronger protective effects on certain parameters, particularly in preserving AMH levels, attenuating fibrosis, and reducing Caspase-3 and NF-κB expression, although the differences between Mel+CARB and GSH+CARB groups were not statistically significant in all comparisons. CONCLUSION: Pre-treatment with melatonin or glutathione effectively mitigated CARB-induced ovarian toxicity by modulating oxidative stress, inflammation, and apoptosis. Melatonin appeared to provide relatively greater protection in some parameters, but without consistent statistical superiority over glutathione. These results underscore the potential of antioxidant-based strategies for fertility preservation during chemotherapy. Further studies with larger sample sizes and direct comparative analyses are warranted to clarify relative efficacy and confirm translational relevance.