Astragalus polysaccharides protect against Di-n-butyl phthalate-induced testicular damage by modulating oxidative stress, apoptosis, and the PI3K/Akt/mTOR pathway in rats.

INTRODUCTION: Di-n-butyl phthalate (DBP), a common plasticizer, is associated with oxidative stress and male reproductive toxicity. Astragalus polysaccharides (APS) have known antioxidative and anti-inflammatory properties, but their role in male reproductive health has not been fully elucidated. METHODS: Twenty-four male rats were randomly assigned to four groups (n = 6 each): control, DBP-only (500 mg/kg/day), APS-only (200 mg/kg/day), and APS + DBP (500 mg/kg/day DBP + 200 mg/kg/day APS). Treatments were administered orally for 8 weeks. Biochemical, histological, and molecular analyses were conducted to evaluate testicular function, oxidative stress markers, and gene expression. RESULTS: DBP exposure significantly decreased serum testosterone levels, catalase (CAT) activity, lactate dehydrogenase (LDH) activity, and sperm quality, while increasing malondialdehyde (MDA) levels and apoptotic markers Casp3, Casp9. APS co-treatment significantly restored antioxidant enzyme activity, improved sperm parameters, reduced MDA levels, and alleviated histopathological damage. Gene expression analysis revealed upregulation of Nrf2 and SOD, and modulation of the PI3K/AKT/mTOR signaling pathway. DISCUSSION: APS exerts protective effects against DBP-induced testicular damage by enhancing antioxidant defenses and regulating key molecular pathways. These findings highlight the therapeutic potential of APS in preventing male infertility associated with environmental toxicants.