DOI: https://doi.org/10.22263/2312-4156.2022.1.31
Husakouskaya E.V., Maksimovich N.Ye.
The effects of isolated and combined administration of L-arginine and aminoguanidine in acute experimental peritonitis
Grodno State Medical University, Grodno, Republic of Belarus
Vestnik VGMU. 2022;21(1):31-41.
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 5 equal series, which were injected intraperitoneally, 0,6 ml/100 g: 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 (300 mg/kg), 4th series – 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.
Key words: experimental peritonitis, leukocytes, NO-synthase, oxidative stress, endothelium, peritoneum, L-arginine, aminoguanidine.
References
1. Gusakovskaia EV, Maksimovich NE. Alternative choice of an adequate method for modeling peritonitis in the experiment. Novosti Med-biol Nauk. 2018;17(2):73-8. (In Russ.)
2. Gusakovskaia EV, Maksimovich NE. Amino acid L-arginine and prospects for its use in clinical practice. Zdravookhranenie. 2003;(5):35-7. (In Russ.)
3. Lazarenko VA, Lipatov VA, Blinkov IuIu, Skorikov DV. Experimental model of widespread fecal peritonitis. Chelovek Ego Zdorov'e. 2008;(4):128-32. (In Russ.)
4. Gusakovskaia EV. Expression of intoxication syndrome in rats with experimental peritonitis and aminoguanidine administration. V: Medzhidov MN, red. Materialy 69-i Vserossiiskoi nauchnoi konferentsii molodykh uchenykh i studentov s mezhdunarodnym uchastiem, Makhachkala, 28 maia 2021 g. Makhachkala, RF: ALEF; 2021. Р. 404-8. (In Russ.)
5. Patcula IuI, Vlasenko VS; Vseros nauch-issled in-t brutselleza i tuberkuleza zhivotnykh Sibir otd-niia Ros akad s/kh nauk, Gorodskaia det klin bol'nitsa № 2 im VP Bisiarinoi, zaiavitel' i patentoobladatel'. Method for determining the functional activity of neutrophils by the reduction reaction of nitroblue tetrazolium: pat RU 2415423S2: MPK G 01 N 33/48. 2011 Mar 27. (In Russ.)
6. Hladovec J, Rossman P. Circulating endothelial cells isolated together with platelets and the experimental modification of their counts in rats. Thromb Res. 1973 Dec;3(6):665-74. doi: http://dx.doi.org/10.1016/0049-3848(73)90014-5
7. Granger DL, Taintor RR, Boockvar KS, Hibbs JB. Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol. 1996;268:142-51. doi: http://dx.doi.org/10.1016/s0076-6879(96)68016-1
8. Rice-Evans CA, Diplock AT, Symons MCR, ed. Laboratory techniques in biochemistry and molecular biology: techniques in free radical research. London: Elsevier; 1991. 291 p.
9. Terentev AA. Biochemistry of muscle tissue: ucheb posobie. Moscow, RF: RNIMU im NI Pirogova; 2019. 76 р. (In Russ.)
10. Satriano J, Schwartz D, Ishizuka S, Lortie MJ, Thomson SC, Gabbai F, et al. Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsi. J Cell Physiol. 2001 Sep;188(3):313-20. doi: http://dx.doi.org/10.1002/jcp.1119
11. Lebedev KA, Poniakina ID. Immunology of pattern recognition receptors. Integral Immunology. Moscow, RF: Librokom; 2017. 256 р. (In Russ.)
12. Sidney, M. M. Jr. Arginine Metabolism. J Nutr. 2016 Dec;146(12):2579S-2586S. doi: http://dx.doi.org/10.3945/jn.115.226621
13. Milosh TS, Maksimovich NE State of the vascular endothelium and prooxidant-antioxidant balance in pregnant rats under conditions of endotoxemia. Patol Fiziologiia Eksperim Terapiia. 2015;59(1):55-9. (In Russ.)
Information about authors:
Husakouskaya E.V. – lecturer of the Chair of Pathological Physiology named after D.A. Maslakov, Grodno State Medical University;
Maksimovich N.Ye. – Doctor of Medical Sciences, professor, head of the Chair of Pathological Physiology named after D.A. Maslakov, Grodno State Medical University,
ORCID: https://orcid.org/0000-0003-3181-9513
Correspondence address: Republic of Belarus, 230009, Grodno, 80, Gorky str., Grodno State Medical University, Chair of Pathological Physiology named after D.A. Maslakov. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Erna V. Husakouskaya.
