کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5661108 | 1590357 | 2017 | 9 صفحه PDF | دانلود رایگان |
ObjectivesTo evaluate the therapeutic potential of I-BET-762, an inhibitor of the bromodomain and extra-terminal (BET) protein family, in experimental acute pancreatitis (AP).MethodsAP was induced by retrograde infusion of taurolithocholic acid sulphate into the biliopancreatic duct (TLCS-AP) or 2 intraperitoneal (i.p.) injections of ethanol and palmitoleic acid 1Â h apart (FAEE-AP) or 12 hourly i.p. injections of caerulein (CER-AP). In all treatment groups, I-BET-762 (30Â mg/kg, i.p.) was administered at the time of disease induction and again 12Â h later. AP severity was assessed at 24Â h by serum biochemistry, multiple cytokines and histopathology.ResultsTLCS-AP, FAEE-AP and CER-AP resulted in characteristic elevations in serum amylase and cytokine levels, increased pancreatic trypsin and myeloperoxidase activity, typical pancreatic histopathological changes and lung injury. Treatment with I-BET-762 significantly reduced biochemical, cytokine and histopathological responses in TLCS-AP and FAEE-AP, but not CER-AP.ConclusionsThese results suggest that in different forms of AP there are significant differences in the epigenetic control of gene transcription contributing to the severity of disease responses. There is therapeutic potential in targeting bromodomains for the treatment of gallstone- and alcohol-related pancreatitis.
Journal: Pancreatology - Volume 17, Issue 5, SeptemberâOctober 2017, Pages 689-697