Comparative protective effects of rosuvastatin and ramipril against doxorubicin-induced testicular toxicity in rats: A multimodal evaluation of oxidative stress and reproductive parameters

Background and Aim: Doxorubicin, a widely used chemotherapeutic agent, is associated with reproductive toxicity due to its induction of oxidative stress and testicular damage. Emerging evidence suggests that rosuvastatin and ramipril may possess antioxidant and cytoprotective properties beyond their conventional uses. However, their comparative efficacy in preventing doxorubicin-induced testicular toxicity remains unclear. This study aimed to evaluate and compare the protective effects of rosuvastatin and ramipril on testicular function, oxidative stress markers, and reproductive outcomes in a rat model of doxorubicin-induced testicular toxicity. Materials and Methods: Twenty-four male Wistar rats were randomly allocated into four groups: Control, doxorubicin-only, rosuvastatin + doxorubicin, and ramipril + doxorubicin. Doxorubicin (5 mg/kg, intraperitoneal) was administered on days 7, 14, and 21, while rosuvastatin or ramipril (5 mg/kg/day, oral) was given for 21 days. On day 45, evaluations included testicular index, sperm count and motility, serum testosterone levels, oxidative stress markers (malondialdehyde [MDA], nitric oxide [NO], glutathione [GSH]), and histopathological analysis using Johnsen scoring. Results: Both rosuvastatin and ramipril significantly restored the testicular index compared to the doxorubicin group (p < 0.05). Ramipril markedly increased serum testosterone, GSH, and NO levels while reducing MDA. Sperm motility and count showed partial improvement, notably in the ramipril group. Histopathological alterations were attenuated in both treatment groups, with improved Johnsen scores and reduced architectural disruption. Conclusion: Ramipril and rosuvastatin mitigate doxorubicin-induced testicular toxicity through antioxidant mechanisms. Ramipril demonstrated superior efficacy in preserving reproductive hormone levels and sperm function. These findings highlight its potential as a fertility-protective agent during chemotherapy. Further long-term and mechanistic studies are warranted.