• Excess consumption of fluorid causes chronic pancreatitis.
• Fraxetin has antioxidant, antiinflammatory, antifibrotic & antiapoptotic activities.
• Driking of water containing NaF for 60 days induced chronic pancreatitis in rats.
• Fraxetin dose dependently alleviated chronic pancreatitis induced in rats by NaF.
• Fraxetin could be a promising agent for NaF induced chronic pancreatitis prevention.

Chronic pancreatitis is considered a common gastrointestinal disorder, with significant morbidity and mortality. Fluoride is an important agent for the development of our body systems, especially for bone and teeth, however on its excess consumption, it deposits in different body tissues, especially the pancreas, causing its chronic inflammation and destruction. Fraxetin proved to possess versatile activities including; antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic activities. In the present study, we have evaluated the fraxetin potentiality to prevent fluoride-induced chronic pancreatitis in rats, by evaluating animal body weights and body weight gain rate, serum amylase, and lipase activities, pancreatic oxidative stress markers, cytokines, apoptotic markers, myeloperoxidase, and hydroxyproline levels, and histopathological changes. Nine-weeks-old male Wistar rats drank distilled water containing 500 ppm sodium fluoride (NaF) for 60 days to induce chronic pancreatitis. Oral fraxetin (20, 40, and 80 mg/kg/day) received simultaneously to prevent chronic pancreatitis development. Fraxetin in a dose-dependent manner alleviated chronic pancreatitis induced by NaF, as it restored the decreased body weight and weight gain rate, decreased the elevated serum amylase and lipase activities, pancreatic IL-6, TNF-?, MDA, caspase-3, MPO and hydroxyproline levels, and Bax/Bcl-2 ratio, enhanced pancreatic CAT and SOD activities, and GSH levels, besides it augmented the elevated IL-10 level, with the restoration of normal pancreatic architecture. Therefore, fraxetin could be a promising agent recommended for the prevention of fluoride-induced chronic pancreatitis in endemic areas.