PANCREATIC FIBROSIS INCREASED AFTER DISCONTINUATION OF PRAVASTATIN TREATMENT IN OLETF RAT

Abstract

Background/Aim: We previously reported that pravastatin treatment exerted beneficial effects on the pancreatic fibrosis in OLETF rats (APA 2004). Although discontinuation or noncompliance of statins seems to be frequent in daily practice, effects of withdrawal of this medicine have been rarely examined to date. In the present study, we sought to clarify whether beneficial effects of pravastatin on pancreatic fibrosis prolong if this treatment is discontinued in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of pancreatic fibrosis. Method: Male OLETF rats were randomly divided into 2 groups at 12 weeks of age. First group received a standard rat diet during experimental period (control). The second group received the diet containing 0.05% pravastatin from 12 to 28 weeks and then switched to a standard rat diet until 80 weeks of age (P12-28W). At age 80 weeks, rats were sacrificed and pancreas was taken. Results: Pancreatic wet weight, DNA content and superoxide dismutase (SOD) activity significantly decreased in the P12-28W compared with those in the control. Pancreatic protein content was lower in the P12-28W than that in the control, and expression level of transforming growth factor-beta 1 mRNA in the pancreas was higher in the P12-28W than that in the control, but statistical significant difference was not obtained. Histological examination revealed that the pancreas was atrophic, and inter- and intraloblar fibrosis were markedly observed in the P12-28W and control. Quantitative evaluation of the rate of fibrosis area using an interactive image analysis system revealed that fibrotic area was significantly increased in the P12-28W compared with that in the control. Conclusion: Present results suggest that discontinuation of pravastatin treatment increased pancreatic fibrosis probably by decreasing SOD activity. Since discontinuation of pravastatin completely abrogated its beneficial effect, discontinuation of this treatment should be avoided.