Background: Despite investigating silver toxicity in other organs, there is a dearth of literature about its effect on the pancreas. Objectives: The current study sought to determine if the antioxidant, anti-inflammatory, and anti-apoptotic properties of sitagliptin (Sit) could protect rats from pancreatic damage caused by silver nitrate (AgNO3). Material and method: In both the presence and absence of AgNO3, Sit was supplied. Four groups of 32 adult albino rats were formed as control, Sit (10mg/kg/ day p.o. for 28 days), AgNO3 (20 mg Ag/kg/day in their drinking water for 28 days), and Sit/AgNO3 (sit + AgNO3 for 28 days) groups. Pancreatic enzymes and blood glucose level (BGL) were measured. In addition to pancreatic oxidative stress, inflammatory, and apoptotic indicators, pancreatic hypoxia-inducible factor 1-alpha (HIF-1α) was assessed. Pancreatic histopathological examination and antiinsulin immunohistochemical study were carried out.

Result: AgNO3 significantly elevated pancreatic enzymes, BGL, pancreatic oxidative stress, inflammatory, apoptotic biomarkers, and HIF-1α expression. Histopathological indicators of pancreatic injury and low antiinsulin expression were found. Sit substantially improved the histological image and mitigated the dispersed pancreatic enzymes, BGL, oxidative stress, inflammatory, and apoptotic indicators, as well as the expression of HIF-1 α. Conclusion: Sit abrogated AgNO3-induced pancreatic toxicity through modulating HIF-1α.