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OBJECTIVES: Granny Smith is a cultivated hybrid variety of apple with a high antioxidant content relative to all other species of apple. Acute pancreatitis (AP) is an instantly emerging inflammatory condition with a high mortality rate. The preferred treatment is restricted to symptomatic relief and supportive care. The present study was undertaken to evaluate the favorable effects of Granny Smith apple extract (GSAE) as a prophylactic treatment for L-arginine-induced AP in rats. MATERIALS AND METHODS: Male Sprague Dawley rats were divided in to five groups (n=6): Normal control (saline), disease control (a single dose of L-arginine 2.5 g/kg I.P.), positive control (pelatonin 10 mg/kg I.P.), and GSAE I and II (200 mg/kg and 400 mg/kg, orally, respectively). All groups were treated for 7 days. At the end of the study, blood samples were collected from the retro-orbital plexus, serum separated, and subjected to estimation of biomarker enzymes such as amylase, lipase, antioxidant enzymes, etc. The animals were then sacrificed, and the pancreas was isolated and subjected to estimation of tissue biomarkers, DNA fragmentation assay, and histopathological studies. RESULTS: Serum levels of amylase and lipase were significantly (p |