Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

Abstract

As appropriate therapies for pancreatic fibrosis and inflammation are limited, prognosis of chronic pancreatitis has not improved to date. Recent studies have shown that statins improve inflammation and fibrosis in several organs. We therefore examined the therapeutic effect of pravastatin on progression of chronic pancreatitis by starting this treatment after induction of pancreatic fibrosis in rats. Chronic pancreatitis was induced by continuous pancreatic ductal hypertension (PDH) for 14 days according to our previous study. Pravastatin at a dose of 10 mg/kg/day was administrated directly into the duodenum via cannula from 2 days after induction of PDH. Progression of pancreatic fibrosis and expression levels of transforming growth factor-b1 and tumor necrosis factor-a mRNA were markedly attenuated after commencement of pravastatin compared with untreated group with PDH. In addition, pravastatin treatment markedly improved pancreatic exocrine function and significantly elevated expression level of interleukin (IL)-10 and superoxide dismutase activity in the pancreas compared with the untreated group with PDH. These results revealed that pravastatin substantially attenuates the progression of pancreatic inflammation, fibrosis and exocrine dysfunction probably by its anti-oxidative property and overproduction of IL-10 in animal model of chronic pancreatitis. These results provide an experimental evidence that pravastatin exerts beneficial effect for progression of chronic pancreatitis.

Antidiabetic and antioxidant effects of catalpol extracted from Rehmannia glutinosa (Di Huang) on rat diabetes induced by streptozotocin and high-fat, high-sugar feed

“…A splenic portion of pancreatic tissue was removed immediately after sacrifice and rinsed with ice-cold saline. The tissue samples were fixed in 4 % buffered neutral paraformaldehyde solution overnight, embedded in paraffin, and deparaffinized using standard procedures [ 20 , 21 ]. Thin Sections (5 µm) were dewaxed, dehydrated in a graded series of ethanol, and rehydrated, then stained with H&E for light microscopic examination (Leica, Germany).…”

A Network Medicine Approach to Drug Repurposing for Chronic Pancreatitis

“…Only 12 reports of statin-induced pancreatitis have been reported [34]. More recent studies have demonstrated that statins may actually have a protective role for CP, attenuating inflammation and fibrosis, most likely due to their antioxidative properties [35].…”

Lipid-Modifying Therapies and Risk of Pancreatitis

“…6,49 Furthermore, studies conducted in animal models suggest that statin therapy may be beneficial in both established acute pancreatitis and chronic pancreatitis. [50][51][52] Major guidelines of lipid-modifying therapy such as the National Cholesterol Education Program Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) 8 and the NationalInstituteforHealthandClinicalExcellence (NICE) Type 2 Diabetes guideline 9 suggesttheadditionoffibratetherapy in patients with moderately elevated triglyceride levels and above (Ͼ400 mg/dL and Ͼ500 mg/dL, respectively). This is based on the rationale that hypertriglyceridemiaisawell-recognizedcauseofpancreatitis and that lowering of triglyceride levels should be clinically beneficial.…”

“…Studies showing associations between statin use and both a reduction in bile cholesterol and reduced risk of gallstones on statins suggest the possibility of a protective effect (6;49). Furthermore, studies conducted in animal models suggest the possibility that statin therapy may be associated with benefit for both acute pancreatitis and chronic pancreatitis (50)(51)(52). suggest that fibrate therapy should be prescribed for patients with moderately elevated triglyceride levels and higher (>500mg/dL and >400mg/dL respectively).…”