The frequency of SPINK 1, PRSS 1 and CFTR mutations in acute pancreatitis

Abstract

Introduction: Melatonin precursor: L-tryptophan protects the pancreas against acute pancreatitis. L-kynuremine (KYN) is the product of L-tryptophan metabolism, but the effect of KYN on acute pancreatitis is unknown. Heat shock proteins (HSP’s) are known as chaperons, saving from harm intracellular compartment. Aims: To assess the effects of KYN on caerulein-induced pancreatitis (AP) in the rats and on HSP60 production in AR42J pancreatic acinar cells. Patients & methods: AP was induced by subcutaneous caerulein infusion (25 microgr/kg). KYN (25, 50 or 100 mg/k) was given intraperitonealy to the rats 30 min prior to the induction of AP. Lipid peroxidation products (MDAþ4HNE) and the activity of an antioxidant enzyme; glutation peroxydase (GPx) were measured in pancreatic tissue. Blood samples were taken for evaluation of amylase and TNF alpha concentrations. HSP60 was determined by Western blot in AR42J cells subjected to KYN (10-12, 10-10, 10-8) without or with addition of caerulein (10-8M). Results: AP was confirmed by histological examination and by the increases of amylase and TNF alpha blood levels (by 800% and 300%, respectively). Pancreatic MDAþ4HNEwas increased by 300%, whereas GPx activity was reduced by 50% in AP rats. KYN significantly diminished histological manifestations of AP, decreased amylase and TNF alpha blood levels, reducedMDAþ4HNE and augmented GPx in the pancreas of AP rats. In AR42J cells KYN alone or combined with caerulein markedly increased HSP60 protein signal. Conclusion: L-kynuremine significantly attenuated acute pancreatitis. This could be related to antioxidative effect of this substance and possibly, to the stimulation of HSP60 by L-kynurenine.