Protective Effects of Rutin and Hesperidin on Cisplatin-Induced Testicular Dysfunction in Rats

Rutin and Hesperidin in Testicular Toxicity

Abstract

Background: Cisplatin is a common chemotherapeutic agent that is known to cause testicular toxicity by oxidative stress, inflammation, and apoptosis, resulting in impaired reproductive function in male patients. Natural flavonoids such as rutin and hesperidin have been shown to have potential protective effects due to their antioxidant properties. Objective: To compare the protective effect of rutin and hesperidin against cisplatin-induced testicular dysfunction in rats. Study Design: Quasi-experimental animal study. Setting: Isra University, Hyderabad Pakistan. Duration: June to November 2025. Methods: A total of 50 adult male Wistar rats were randomly divided into 5 groups (n = 10). Group A was the control, Group B received cisplatin (7 mg/kg, one intraperitoneal dose), and Groups C, D, and E received cisplatin followed by hesperidin (50 mg/kg/day), rutin (75 mg/kg/day), and their combination, respectively, for one month. Serum reproductive hormone levels, oxidative stress markers, sperm parameters, and histopathological changes were assessed. One-way ANOVA and Tukey's post hoc test were used to conduct the statistical analysis. Results: Cisplatin significantly decreased the body and testicular weights, reproductive hormones, and sperm parameters, and increased oxidative stress and histopathological damage (p < 0.001). The combination of rutin and hesperidin significantly enhanced these parameters (p < 0.05), with the combination group showing near-normal restoration and the most significant protective effects. Conclusion: Rutin and hesperidin are effective in reducing cisplatin-induced testicular dysfunction, possibly via antioxidant and cytoprotective actions, with combination therapy proving most effective.