NITROSO-OXIDATIVE PROCESSES IN DIGESTIVE ORGANS UNDER THE CONDITION OF EXPERIMENTAL DIABETES AND ACTION OF L-ARGININE AND AMINOGUANIDINE
Aim of the investigation: considering that nitrogen oxide, which is synthesized by constitutive isoforms of NO-synthase (cNOS) of the digestive tract is included in the regulatory mechanisms of secretion (gastric and intestinal glands, as well as the pancreas), maintaining the structure and functions of the mucous barrier, regulation processes of intercellular integration, modulation of nerve signal transmission in non-adrenergic noncholinergic neurons, influence on the state of microbiocenosis and motor activity of the stomach and intestine, its role in experimental diabetes is a subject of in-depth examination. Thus, the aim of the study was to examine the changes of activiy of NO-synthases and lipoperoxidation processes in mucosal and muscle membranes of stomach and large intestine and the tissue of pancreas under the condition of experimental strptozotocin-induced diabetes and action of L-arginine and aminoguanidine.
Materials and methods. The studies were performed on 48 white rats, that were divided into four groups: the first - control group of an animals to which the corresponding volume of physiological solution was injected; the second - animals with experimental diabetes mellitus (induced by administration of streptozotocin intraperitoneally); the third - animals with diabetes, to which for two weeks intraperitoneally L-arginine was injected; the fourth - animals with diabetes, to which for two weeks intraperitoneally a selective inhibitor of inducible NO synthase (iNOS) aminoguanidine was administered. L-arginine and aminoguanidine were administered 14 days after the formation of streptozotocin-induced diabetes in animals. Activity of NO-synthases, arginase and concentration of nitrite-anion and malonic dialdehyde were measured in mucosal and muscle membranes of stomach and large intestine and the tissue of pancreas on 28 day of experiment.
Results. The introduction of streptozotocin led to the increase of the activity of the inducible NO-synthase and nitrite anion production, concentration of malonic dialdehyde, the decrease of constitutive NO-synthase activity and arginase. The content of L-arginine and the activity of pancreatic α-amylase in blood plasma became lower as well. The introduction of L-arginine under background of experimental diabetes caused the decrease of glucose concentration, the increase of L-arginine content in blood plasma and decrease in malonic aldehyde and nitrite-anion production as well as inducible NO-synthase activity in organs of digestive system. The introduction of aminoguanidine led to the decrease of nitrite-anion production because of inducible NO-synthase inhibition, the decrease in malonic aldehyde concentration and the activity of antioxidant system enzymes. Thus, the positive effect of L-arginine in diabetes mellitus in the digestive system is associated with reduced oxidative processes and production of superoxide radical, iNOS activity, increased superoxide dismutase and catalase activity, increased formation of polyamines, stimulation of insulin secretion by pancreatic β-cells, reduction of insulin level in blood, increasing the transport of glucose and its assimilation by cells, promoting the motility.
Conclusions. Modeling of NO-synthase system by substrate and inhibitor may normalize metabolic changes in organs of digestive system, caused by the development of streptozitocin-induced diabetes in rats.
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