The effect of acute alcohol intoxication on trypsin activity and hemostasis parameters in rats

Introduction. Acute alcohol intoxication (AAI) causes multifactorial damage to organs and tissues. While the clinical manifestations and complications associated with AAI are well known, the underlying mechanisms remain poorly understood.

Objective. Studying of the AAI influence on activity of trypsin and indicators of a hemostasis.

Materials and methods. AAI was induced by intraperitoneal administration of ethanol (5 g/kg). After 24 hours, trypsin activity was determined in serum, and fibrinogen content and coagulation status were determined in plasma.

Results. In rats with AAI, trypsin activity was increased more than doubled in serum. Trpsin, according to current concepts, is a protease-activated receptor (PAR) agonist. The plasma fibrinogen level increased (p < 0.05), indicating activation of the blood coagulation system and a high risk of thrombotic and thromboembolic complications.

Conclusion. Data about the sharp increase of the trypsin serum concentrations, an endogenous agonist of PARs receptors, in animals with AAI, raises the question of the contribution of PARs to the development of multiorgan pathology pathognomonic of AAI.

1. Akalaev RN, Stopnitskii AA, Khozhiev KhSh. Ostrye otravleniya alkogolem. Epidemiologiya, diagnostika, lechenie i analiz nereshennykh problem. Vestnik ekstrennoi meditsiny. 2017;X(1):104-111. (In Russ.).

2. Khodos OA, Gidranovich LG, Sachek MM. Aktivnost' proteinaz i ikh endogennykh ingibitorov v ekstrakte tkani golovnogo mozga i syvorotke krovi krys pri ostroi alkogol'noi intoksikatsii. Vestnik VGMU. 2011;10(2):20-25. (In Russ.).

3. Berberidy HP, Popov KA, Bykov IM, et al. Features of changes in biochemical indicators in rats with alcohol intoxication on the background of correction with use of lipoic acid. Krymskii zhurnal eksperimental'noi i klinicheskoi meditsiny. 2019;9(3):13-18. (In Russ.).

4. Ossovskaya VS, Bunnett NW. Protease-activated receptors: contribution to physiology and disease. Physiol Rev. 2004 Apr;84(2):579-621. doi: 10.1152/physrev.00028.2003.

5. Soh UJ, Dores MR, Chen B, Trejo J. Signal transduction by proteaseactivated receptors. Br J Pharmacol. 2010 May;160(2):191-203. doi: 10.1111/j.1476-5381.2010.00705.x.

6. Shah R. Protease-activated receptors in cardiovascular health and diseases. Am Heart J. 2009 Feb;157(2):253-62. doi: 10.1016/j.ahj.2008.09.025.

7. Hansen KK, Oikonomopoulou K, Li Y, Hollenberg MD. Proteinases, proteinase-activated receptors (PARs) and the pathophysiology of cancer and diseases of the cardiovascular, musculoskeletal, nervous and gastrointestinal systems. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):377-92. doi: 10.1007/s00210-007-0194-2.

8. Chandrabalan A, Ramachandran R. Molecular mechanisms regulating Proteinase-Activated Receptors (PARs). FEBS J. 2021 Apr;288(8):2697-2726. doi: 10.1111/febs.15829.

9. Kuzmina IV, Ovchinnikova NV, Tolpygo SM. Serum activity of proteolytic enzyme trypsin in rats under conditions of water and food deprivation. Bulletin of Experimental Biology and Medicine. (In Russ.). doi: 10.47056/0365-9615-2023-175-5-540-544. EDN: VKSBIT

10. Mrozkova P, Palecek J, Spicarova D. The role of protease-activated receptor type 2 in nociceptive signaling and pain. Physiol Res. 2016 Jul 18;65(3):357-67. doi: 10.33549/physiolres.933269.

11. Peach CJ, Edgington-Mitchell LE, Bunnett NW, Schmidt BL. Protease-activated receptors in health and disease. Physiol Rev. 2023 Jan 1;103(1):717-785. doi: 10.1152/physrev.00044.2021.

12. Steinberg SF. The cardiovascular actions of protease-activated receptors. Mol Pharmacol. 2005 Jan;67(1):2-11. doi: 10.1124/mol.104.003103.

13. Pawlinski R, Tencati M, Hampton CR, et al. Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy. Circulation. 2007 Nov 13;116(20):2298-306. doi: 10.1161/CIRCULATIONAHA.107.692764.

14. Antoniak S, Sparkenbaugh EM, Tencati M, et al. Protease activated receptor-2 contributes to heart failure. PLoS One. 2013 Nov 27;8(11):e81733. doi: 10.1371/journal.pone.0081733.

15. Uehara Y, Miura S, Yahiro E, Saku K. Non-ACE pathway-induced angiotensin II production. Curr Pharm Des. 2013;19(17):3054-9. doi: 10.2174/1381612811319170012.

16. Vernigora AN. Effect of ethanol administration on carboxypeptidase H and angiotensin converting enzyme activities in some brain regions of the rats with different stability to stress. Izv. Penz. gos. pedagog. univ. im. i. V. G. Belinskogo. 2010;17(21):101-103. (In Russ.).

17. Timofeev AV. Basic carboxypeptidases of blood: significance for coagulology. Biomeditsinskaya khimiya. 2016;62(2);141-149. (In Russ.). doi: 10.18097/PBMC20166202141.