Ameliorative potential of silymarin against lead-induced parotid gland injury: Exploring key mechanistic insights.

Lead is a widespread environmental contaminant that induces multi-organ toxicity primarily through oxidative damage and inflammatory responses. Salivary glands particularly the parotid are increasingly recognized as vulnerable targets of metal-induced injury, with significant implications for oral and digestive health. This study investigated the protective effect of silymarin, a flavonolignan antioxidant extracted from milk thistle seeds, against lead acetate-induced parotid gland damage in rats. Forty adult male Wistar rats were allocated into four groups: untreated controls, silymarin only (100 mg/kg), lead acetate only (50 mg/kg), and a combined treatment group receiving silymarin (100 mg/kg) and lead acetate (50 mg/kg). Treatments were administered orally for six consecutive weeks. Parotid tissues were evaluated using histology, immunohistochemistry, ELISA, qRT-PCR, and transmission electron microscopy (TEM). Lead acetate exposure caused extensive tissue injury, including acinar vacuolation, ductal dilation, and vascular congestion, accompanied by elevated lipid peroxidation, depletion of endogenous antioxidant enzymes, activation of inflammatory signaling pathways, and upregulation of pyroptotic, apoptotic, and ferroptotic markers. TEM revealed swollen mitochondria with fragmented cristae in lead-exposed glands, hallmarks of ferroptosis. Fibrotic remodeling with collagen accumulation was also evident. Silymarin co administration was associated with significant attenuation of these pathological alterations, correlating with enhanced antioxidant defenses, reduced inflammatory mediators, lowered expression of markers linked to multiple programmed cell death pathways, and decreased fibrosis. TEM confirmed silymarin preserved mitochondrial cristae integrity. In summary, these findings suggest that silymarin may exert broad cytoprotective effects against lead induced parotid gland injury, potentially involving coordinated effects on oxidative stress, inflammation, cell death pathways, and fibrotic responses. This points to its potential therapeutic value in heavy metal toxicity, pending further validation.