INVESTIGATION OF THE INFLUENCE OF HYDROGEN SULFIDE DONORS ON THE LEVEL OF OXIDATIVE STRESS UNDER CONDITION OF ACUTE PANCREATITIS IN RATS
About the author:
Bondarchuk T. I., Fomenko I. S.
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Acute pancreatitis is a severe inflammatory process of pancreas, characterized by the activation of pancreatic digestive zymogens within the pancreatic acinar cell. The main factors responsible the systemic progression of inflammatory process include pro-inflammatory cytokines, chemokines, reactive oxygen species and nuclear factor NKκB. It was recently demonstrated that H2 S plays a vital role in the pathogenesis of acute pancreatitis. Thus, the principal objective of this study was to evaluate the action of a H2 S donors (NaHS and L-cysteine) on parameters of oxidative stress and myeloperoxidase activity in pancreas of rats under condition of acute pancreatitis induced by L-ornithine. Methods. The structure of this study and the experimental procedures performed on the animals were approved by the Ethical Committee of Lviv National Medical University. The experimental procedures were carried out in accordance with the international guidelines for the use and care of laboratory animals. Male, outbred albino rats weighing 180-200 g were used. Rats were randomly divided into 4 experimental groups (8 animals in each group). Group 1 consisted of control rats. L-ornithine was introduced to rats of groups 2-4 at a dose 10 mg/kg to induce acute pancreatitis. Rats of group 3 were pretreated with a donor of H2 S – NaHS at a dose 10 mg/kg. Rats of group 4 were given a precursor of H2 S synthesis – L-arginine at a dose 30 mg/kg. In the homogenates of pancreas were determined: malonic dialdehyde (MDA) concentration in the reaction with thiobarbituric acid, activity of myeloperoxydase, superoxide dismutase (SOD), catalase. H2 S concentration was determined in blood plasma. Results. It was shown that under condition of the induction of acute pancreatitis by ornithine, activity of myeloperoxidase increased almost three-fold, p˂0,01as compared to the control group, indicating the development of inflammatory process in the pancreas. Administration of NaHS and L-cysteine led to the decrease of myeloperoxidase activity as compared to parameters of the 2nd group. Myeloperoxidase activity was decreased by 40 and 48%, subsequently, p<0,01. The development of acute pancreatitis was accompanied by the formation of oxidative stress in the pancreas, manifested by two-fold (p<0,01) increase of MDA concentration. NaHS decreased MDA concentration by 40%, p<0,01, L-cysteine by 11,5% as compared to parameters of rats with acute pancreatitis. Such a decrease in MDA concentration under condition of the use of Н2 S donors may demonstrate the antioxidant properties of this gaseous mediator. Activity of one of the most important enzymes of antioxidant system SOD was reduced by 40%, p<0,01 in homogenates of pancreas of rats with acute pancreatitis, since the introduction of NaHS and L-cysteine increased it. Catalase activity as well as SOD activity decreased in acute pancreatitis (by 33%, p<0,01) however it demonstrated only the tendency to the increase in groups of animals treated by H2 S donors. H2 S concentration in blood plasma of animals of the 2nd group decreased by 16%, leading to the disappearance of hydrogen sulfide antioxidant and anti-inflammatory properties in acute pancreatitis. H2 S donors significantly increased it. Conclusion. The induction of acute pancreatitis by L-ornithine was accompanied by the development of oxidative stress in pancreas manifested by the increase of MDA concentration and the decrease of SOD and catalase activities. H2 S donors demonstrated beneficial effects, decreasing the level lipid peroxidation, inducing activities of antioxidant enzymes and possessing anti-inflammatory action by the decrease of myeloperoxidase activity. Thus, H2 S-releasing compounds in physiological doses may create new pharmacological approaches in the treatment of inflammation in acute pancreatitis.
pancreas, acute pancreatitis, hydrogen sulfide, oxidative stress.
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Publication of the article:
«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 98-102 pages, index UDK 577.1:546.221.1: 616.37-002-036.11-092.9