PRAVASTATIN ATTENUATES PANCREATIC FIBROSIS IN OLETF RAT.

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Background/Aim: Appropriate therapies for chronic pancreatitis are still limited and pancreatic fibrosis is irreversible. There are increasing evidence that statins exert beneficial effects, such as anti-inflammatory, anti-fibrotic or anti-oxidant actions beyond cholesterol reduction. We therefore investigated the effect of pravastatin on the pancreatic fibrosis, using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of pancreatic fibrosis. Method: Male OLETF rats were randomly divided into 3 groups at 12 weeks of age. First group received a standard rat diet (control). Second group was given a diet containing 0.05 % pravastatin from 12 weeks of age, before the onset of pancreatic fibrosis (12W-p). Third group was maintained on the same diet containing pravastatin from 28 weeks of age, after the onset of pancreatic fibrosis (28W-p). At age 72 weeks, rats were sacrificed and pancreas was taken. Results: Pancreatic wet weight and contents of protein, enzymes and DNA significantly increased in both 12W-p and 28W-p compared with control. Histological examination revealed that the pancreas was atrophic, and inflammatory cell infiltrations and inter- and intralobular fibrosis were markedly observed in control. In addition, immunohistochemistry demonstrated that expressions of collagen type I, type III, fibronectin and α -smooth muscle actin were markedly increased. These histological alterations remained minimum in both 12W-p and 28W-p. Quantitative real-time RT-PCR showed that expression of message level for TGF-β1 in the pancreas was significantly decreased in both 12W-p and 28W-p compared with control. Conclusions: Present results suggest that pravastatin exerts both preventive and therapeutic effects on pancreatic fibrosis via probably anti-inflammatory effect in OLETF rat. Our results may support the clinical use of pravastatin for chronic pancreatitis.