Melphalan-Induced Ovarian Toxicity and Effects of Chrysin in an Experimental Rat Model: The Role of Oxidative Stress and MicroRNA in Regulating Autophagy

Introduction: This study aims to investigate the microRNA-modulatory effects of chrysin in mitigating melphalan-induced ovarian damage. Methods: Rats were divided into six groups: Group 1: Control; Group 2: Melphalan (1.5 mg/kg); Group 3: Melphalan (1.5 mg/kg) + Chrysin (50 mg/kg); Group 4: Melphalan (1.5 mg/kg) + Chrysin (75 mg/kg); Group 5: Chrysin (50 mg/kg); Group 6: Chrysin (75 mg/kg). Melphalan was administered via injection, while chrysin was given orally by gavage daily for two weeks. Results: The results showed that melphalan-induced ovarian toxicity impaired folliculogenesis and decreased the expression of miR-30a, miR-375, and miR-204, leading to increased autophagy and cell death. High-dose chrysin treatment appeared to counteract these effects by modulating oxidative stress markers (MDA, SOD, GPX) and restoring microRNA expression, thereby reducing cell death during folliculogenesis. Discussion: Chrysin, in addition to its antioxidant effects, influences biological processes through miRNA regulation. Specifically, miR-30a, miR-375, and miR-204 suppress autophagy-related genes. By modulating the levels of these miRNAs, chrysin helps reduce ovarian folliculogenesis impairment and ultimately prevents excessive autophagy. Conclusion: These findings suggest that high-dose chrysin treatment may offer a potential therapeutic option for protecting ovarian tissue from melphalan-induced toxicity by modulating microRNAs and Oxidative Stress.