Changes of oxidative stress, inflammatory mediators and malnutrition in acute and chronic pancreatitis

The pathogenesis and dietotherapy of different forms of pancreatitis has been studied. In the framework of the experimental part the acute pancreatitis was induced in rats by administration of excessive doses of lysine and arginine, and the secretory and morphological changes were investigated. A direct non-specific membrane damaging and cell-necrotizing effect of these amino acids has been confirmed. These experimental models may be useful for investigating different factors playing role in the development of acute necrotising pancreatitis.;In the clinical examinations, effect of early enteral nutrition was studied in patients with acute pancreatitis treated at the Department of Gastroenterology of MAV Hospital. A correlation between the early jejunal feeding and changes of inflammatory mediator release, oxidative stress and nutritional status was examined. The antioxidant and nutritional status were also measured in patients suffering from chronic pancreatitis. In spite of early enteral nutrition the levels of cytokines remained high with slow recovery in patients with severe and complicated acute pancreatitis. Measuring the level of primary antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPOX), the total antioxidant status (TAS) of the serum, a reduced antioxidant defense was found in comparison to control group already at admission and during the treatment. The reduced SOD activity significantly correlated with the severity of the disease and with the frequency of complications. The antioxidant status of patients did not fully normalize in spite of clinical recovery. The deterioration of acute protein-energy malnutrition educed by catabolic stress and inflammation was prevented by jejunal feeding. First in the literature, we studied the effect of enterally supplemented n-3-PUFAs (3,3 g/day) in acute pancreatitis. The n-3 to n-b PUFA ratios increased significantly in serum lipids of the patients. As a result of the treatment the length of jejunal feeding and hospital stay was significantly reduced.;At the examination of patients suffering from chronic pancreatitis, a significant decrease of SOD activity was observed, however, this decrease was milder in comparison to acute pancreatitis. In chronic pancreatitis 24% of patients had moderate or high risk of PEM. The frequency of protein malnutrition was significantly higher in patients with alcohol induced chronic pancreatitis.;The final part of the thesis---based on the results of experiments discussed above---summarizes the principles of dietary treatment of patients, suffering from acute and chronic pancreatitis, emphasizing the supplementation with antioxidants and n-3-PUFAs.