Nanopropolis mitigates cisplatin-induced submandibular gland injury by modulating oxidative stress and apoptosis

Cisplatin is a widely deployed chemotherapeutic agent whose clinical utility is constrained by dose-limiting toxicities, including injury to the submandibular salivary gland mediated primarily by oxidative stress-driven apoptosis and progressive fibrotic remodeling. This study investigated the protective potential of Nanopropolis against cisplatin-induced structural, molecular, and ultrastructural alterations in the rat submandibular gland. Thirty adult male albino rats were allocated into three groups (n = 10): control, cisplatin-treated (single intraperitoneal injection, 8 mg/kg), and cisplatin + Nanopropolis (10 mg/kg/day orally for 14 days). Glandular injury was evaluated by hematoxylin and eosin histology, Masson’s trichrome histochemistry, BAX immunohistochemistry, transmission electron microscopy, and quantitative real-time PCR for SOD1 mRNA. Cisplatin induced marked glandular pathology characterized by acinar degeneration, cytoplasmic vacuolation, ductal disruption, vascular congestion, and extensive collagen accumulation (29.66% of tissue area). These changes were accompanied by strong BAX upregulation and profound SOD1 mRNA suppression (0.223-fold vs. control), reflecting heightened apoptotic activity and oxidative stress. Nanopropolis treatment substantially reversed these findings, preserving glandular architecture, reducing collagen deposition to 5.72%, downregulating BAX expression, and restoring SOD1 expression to near-control levels (1.042-fold). TEM confirmed recovery of mitochondrial cristae integrity, secretory granule content, and ductal basal infoldings. Nanopropolis confers robust cytoprotection against cisplatin-induced submandibular gland toxicity by simultaneously attenuating oxidative stress, suppressing apoptotic signaling, and limiting fibrotic remodeling. These findings support Nanopropolis as a promising adjunctive strategy for preserving salivary gland integrity during cisplatin-based chemotherapy.