Hormonal protection in acute pancreatitis by ghrelin, leptin and melatonin.

Acute pancreatitis is a nonbacterial disease of the pancreas. The severe form of this ailment is characterized by high mortality. Whether acute pancreatitis develops as the severe type or resolves depends on the intensity of the inflammatory process which is counteracted by the recruitment of innate defense mechanisms. It has been shown that the hormones ghrelin, leptin and melatonin are able to modulate the immune function of the organism and to protect the pancreas against inflammatory damage. Experimental studies have demonstrated that the application of these substances prior to the induction of acute pancreatitis significantly attenuated the intensity of the inflammation and reduced pancreatic tissue damage. The pancreatic protective mechanisms of the above hormones have been related to the mobilization of non-specific immune defense, to the inhibition of nuclear factor kappa B and modulation of cytokine production, to the stimulation of heat shock proteins and changes of apoptotic processes in the acinar cells, as well as to the activation of antioxidant system of the pancreatic tissue. The protective effect of ghrelin seems to be indirect and perhaps dependent on the release of growth hormone and insulin-like growth factor 1. Leptin and ghrelin, but not melatonin, employ sensory nerves in their beneficial action on acute pancreatitis. It is very likely that ghrelin, leptin and melatonin could be implicated in the natural protection of the pancreatic gland against inflammatory damage because the blood levels of these substances increase in the initial phase of pancreatic inflammation. The above hormones could be a part of the innate resistance system which might remove noxious factors and could suppress or attenuate the inflammatory process in the pancreas.

Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)-2 and inhibits heat shock protein HSP70 in gastric cancer epithelial cells.

OBJECTIVE: Apoptosis plays an important role in the regulation of gastric epithelial cell number and gastrointestinal disorders induced by Helicobacter pylori (Hp). Heat shock proteins (HSPs) are involved in cell integrity, cell growth and in gastric mucosa colonized by Hp. COX-2 was implicated in Hp-induced carcinogenesis but the effects of this germ and CagA cytotoxin on HSP70, COX-2, Bax and Bcl-2 in gastric cancer epithelial cells have been little studied. MATERIAL AND METHODS: We determined the expression for HSP70, Bax and Bcl-2 in human gastric epithelial MKN7 cells incubated with live strain Hp (cagA + vacA+) with or without co-incubation with exogenous CagA and NS-398, the selective COX-2 inhibitor. After 3-48 h of incubation, the expression of HSP70, COX-2, Bax and Bcl-2 mRNA and proteins were determined by RT-PCR and immunoprecipitation. RESULTS: Hp inhibited expression for HSP70 and this was significantly potentiated by exogenous CagA. Co-incubation of epithelial cells with Hp, without or with CagA increased Bax expression and simultaneously decreased expression for Bcl-2. The increase in COX-2 mRNA and Bax expression were significantly inhibited by NS-398. We conclude that Hp promotes apoptosis in adenocarcinoma gastric epithelial cells in vitro and this is associated with activation of COX-2 and inhibition of HSP70.

Melatonin as an organoprotector in the stomach and the pancreas.

Melatonin was thought to originate primarily from the pineal gland and to be secreted during the night, but recent studies revealed that gastrointestinal (GI) tract presents another, many times larger, source of melatonin that contributes significantly to the circulating concentration of this indole. Melatonin may exert a direct effect on GI tissues but its major influence on GI organs seems to occur indirectly, via the brain-gut axis including peripheral receptors, sensory afferent (vagal or sympathetic) pathways and central nervous system (CNS) acting on these organs via autonomic efferents and neuromediators. This article reviews and updates our experience with the fascinating molecule, as related to GI organs, with special focus on secretory activity of the stomach and pancreas and the maintenance of their tissue integrity. In addition to being released into the circulation, melatonin is also discharged into the gut lumen and this appears to be implicated in the postprandial stimulation of pancreatic enzyme secretion, mediated by melatonin-induced release of cholecystokinin, acting through entero-gastro-pancreatic reflexes. Although exerting certain differences in the mechanism of action on gastric and pancreatic secretory activities, melatonin derived from its precursor L-tryptophan, exhibits similar highly protective actions against the damage of both the stomach and the pancreas and accelerates the healing of chronic gastric ulcerations by stimulating the microcirculation and cooperating with arachidonate metabolites such as prostaglandins, with nitric oxide released from vascular endothelium, and/or sensory nerves and with their neuropeptides such as calcitonin gene related peptide. The beneficial effects of melatonin results in gastro- and pancreato-protection, prevents various forms of gastritis and pancreatitis through the activation of specific MT2-receptors and scavenges reactive oxygen species (ROS). Melatonin counteracts the increase in the ROS-induced lipid peroxidation and preserves, at least in part, the activity of key anti-oxidizing enzymes such as superoxide dismutase. It is proposed that melatonin should be considered as the agent exerting an important role in prevention of gastric and pancreatic damage and in accelerating healing of gastric ulcers.

[Protective and therapeutic effect of leptin in acute pancreatitis evoked by ischemia/reperfusion]. / Ochronny i leczniczy wplyw leptyny w ostrym zapaleniu trzustki wywolanym ischemia z reperfuzja.

Leptin is a hormone implicated in the regulation of the food intake and body weight, but also increasing number of evidence suggest that leptin participates in the regulation of inflammatory processes. The aim of our study was to examine the influence of exogenous leptin administration on the development and the course of acute ischemic pancreatitis. Acute pancreatitis was induced by temporary limitation of pancreatic blood flow, followed by reperfusion. Leptin was administered three times daily at the dose 10 or 50 micrograms/kg. Studies were terminated at 1, 3, 5, 10 and 21 days after induction of acute pancreatitis. Leptin administration reduced development of pancreatic damage and accelerated pancreatic regeneration. It was manifested by the decrease in serum lipase and amylase activity, the reduction in serum interleukin-1 beta concentration and the improvement of pancreatic histology. Additionally, treatment with leptin caused the increase in the pancreatic blood flow and pancreatic DNA synthesis. Serum interleukin-10 concentration was not effected by leptin administration. Leptin at the dose 50 micrograms/kg was more effective than 10 micrograms/kg. We conclude that leptin is able to limit the pancreatic damage in the course of ischemic pancreatitis and accelerates the pancreatic tissue repair. These effects of leptin seem to be dependent on the increase in pancreatic cell growth, the limitation of pro-inflammatory interleukin-1 beta release and the improvement of pancreatic blood flow.