Hashmi_2026_Naunyn.Schmiedebergs.Arch.Pharmacol__

This study aimed to formulate diosgenin-loaded niosomes (DGN) and evaluate their protective effects against cadmium chloride (CdCl(2))-induced neurological and endocrine disruption in female Wistar rats. DGN niosomes were prepared using the film hydration technique. CdCl(2) (0.5 mg/kg/day) was orally administered for 45 days to induce toxicity, while treatment groups received DGN niosomes (1.5, 3, and 6 mg/kg/day) and the standard group received lycopene (10 mg/kg/day). The oxidative stress biomarkers were analyzed in the brain, ovaries, and sciatic nerve, along with neurotransmitters (norepinephrine, dopamine, serotonin), behavioral parameters, hormonal levels (LH, FSH, progesterone, testosterone), and acetylcholinesterase activity. Inflammatory and apoptotic markers (TNF-alpha, NF-kappaB, caspase-3, IL-6, Nrf2, BCL-2, and Bax) were also assessed, supported by histopathological evaluation. CdCl(2) exposure caused significant oxidative stress, neurotransmitter imbalance, behavioral impairment, hormonal disruption, and tissue damage. The treatment with DGN niosomes restored antioxidant status, improved neurotransmitter levels and behavioral performance, normalized hormonal balance, reduced acetylcholinesterase activity, and downregulated inflammatory and apoptotic markers. Histological analysis confirmed marked protection of brain, ovarian, and sciatic nerve tissues. DGN niosomes effectively attenuated CdCl(2)-induced neurotoxicity, reproductive dysfunction, and peripheral neuropathy by reducing oxidative stress, inflammation, and apoptosis.