Quercetin attenuates busulfan-induced testicular and epididymal toxicity via modulation of oxidative stress, inflammatory cytokines, and apoptotic markers in rats

Abstract

Background

Busulfan, an alkylating chemotherapeutic agent, is associated with male reproductive toxicity, including impaired spermatogenesis and hormonal imbalance. This study aimed to investigate the protective effects of quercetin, a natural antioxidant flavonoid, against busulfan-induced testicular and epididymal damage in adult male rats.

Methods

Forty adult male albino rats were randomly divided into four groups: Control, Quercetin (70 mg/kg), Busulfan (10 mg/kg), and Quercetin + Busulfan. Treatments were administered orally for four weeks. Testicular and epididymal tissues were evaluated histologically, and sperm parameters, oxidative stress markers (MDA, SOD), inflammatory cytokines (TNF-α, IL-10), apoptotic proteins (caspase-3, Bax), antiapoptotic (BCL-2) and serum sex hormones (testosterone, LH,and FSH) were assessed.

Results

Busulfan significantly impaired testicular architecture, reduced sperm count and motility, increased MDA levels, and decreased SOD activity. It also elevated pro-inflammatory cytokines and pro-apoptotic markers while suppressing serum testosterone, LH, and FSH levels (p < 0.05). Co-administration of quercetin markedly alleviated histopathological damage, restored sperm quality, reduced oxidative and inflammatory markers, and normalized hormone levels.

Conclusion

Quercetin demonstrates significant protective effects against busulfan-induced testicular and epididymal toxicity, likely through its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. These findings support the potential use of quercetin as an adjuvant therapy to mitigate chemotherapy-induced male infertility.