THE EFFECTS OF ISOLATED AND COMBINED ADMINISTRATION OF L-ARGININE AND AMINOGUANIDINE IN ACUTE EXPERIMENTAL PERITONITIS

Abstract

Objectives. To study the effects of isolated and combined administration of L-arginine and aminoguanidine in acute experimental peritonitis. Material and methods. Experiments were conducted on white male rats (n=185), divided into 5equal series, which were injected intraperitoneally, 0,6ml/100g: the 1st series (control) - 0.9%NaCl, the 2nd (experimental peritonitis, EP) - the 5th series - 15% fecal suspension, with intramuscular injection to rats of the 3rd series with: substrate of NO-synthase (NOS) - L-arginine, L-Arg (300mg/kg), 4thseries - inhibitor of inducible NOS - aminoguanidine, AG (15 mg/kg), the 5th series - L-Arg and AG in analogous doses. The signs of intoxication syndrome, changes in leukocyte differential count and peritoneal fluid, the severity of prooxidant-antioxidant imbalance, lesions of vascular endothelium and structural changes in the peritoneum were studied. Results. The research of the EP course in rats with combined administration of L-Arg and AG revealed in the presence of more significant corrective effect, in comparison with the results in EP with their isolated use, showing up in the increase of motor activity and muscular strength, normalization of breathing and thermoregulation, decrease in the severity of leukocytosis and nuclear shift of the leukogram to the left, increase in the phagocytic activity, decline in the concentration of nitrite/nitrates and malondialdehyde, increased level of reduced glutathione, decrease in the quantity of circulating endothelial cells in blood and structural disorders in peritoneum. Conclusions. The most pronounced corrective effect of combined administration of the NOS-substrate, L-Arg, and the inhibitor of its inducible isoform, AG, in rats with EP may result from the suppression of excessive NO production by AG, as well as the maintenance of the constitutive NOS-activity and various metabolic pathways in the course of L-Arg administration.