MELATONIN METABOLITE, N-1-ACETYL-N-1-FORMYL-5-METHOXYKYNURAMINE (AFMK), ATTENUATES ACUTE PANCREATITIS IN THE RAT: IN VIVO AND IN VITRO STUDIES

作者：Jaworek J; Szklarczyk J; Bonior J; Kot M; Goralska M; Pierzchalski P; Reiter R J; Czech U; Tomaszewska R

来源：Journal of Physiology and Pharmacology, 2016, 67(3): 411-421.

• acute pancreatitis
• melatonin
• N-1-acetyl-N-2-formyl-5-methoxykynuramine
• apoptosis
• antioxidant
• tumor necrosis factor-alpha
• lipid peroxidation

Melatonin protects the pancreas from inflammation and free radical damage but the effect of the melatonin metabolite: N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) on acute pancreatitis is unknown. This study assessed the effects of AFMK on acute pancreatitis (AP) in the rats in vivo and on pancreatic cell line AR42J in vitro. AFMK (5, 10 or 20 mg/kg) was given intraperitoneally to the rats 30 min prior to the induction of AP by subcutaneous caerulein infusion (25 mu g/kg). Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue. Blood samples were taken for evaluation of amylase activity and TNF-alpha concentration. GPx, TNF-alpha, proapoptotic Bax protein, antiapoptotic Bcl-2 protein and the executor of apoptosis, caspase-3, were determined by Western blot in AR42J cells subjected to AFMK or to melatonin (both used at 10(-12),10(-10), or 10(-8)M), without or with addition of caerulein (10(-8)M). AP was confirmed by histological examination and by serum increases of amylase and TNF-alpha (by 800% and 300%, respectively). In AP rats, pancreatic MDA + 4-HNE levels were increased by 300%, whereas GPx was reduced by 50%. AFMK significantly diminished histological manifestations of AP, decreased serum amylase activity and TNF-a concentrations, reduced MDA + 4-HNE levels and augmented GPx in the pancreas of AP rats. In AR42J cells, AFMK combined with caerulein markedly increased protein signals for GPx, Bax, caspase-3 and reduced these for TNF-a and Bcl-2. In conclusion, AFMK significantly attenuated acute pancreatitis in the rat. This may relate to the antioxidative and anti-inflammatory effects of this molecule and possibly to the stimulation of proapoptotic signal transduction pathway.

• 出版日期2016-6