Pathophysiology
doi: 10.25005/2074-0581-2024-26-3-417-426
EVALUATION OF PROTEOLYTIC ACTIVITY IN EXPERIMENTAL PERITONITIS WITH SEROGUARD® TREATMENT
1Irkutsk Scientific Center for Surgery and Traumatology, Irkutsk, Russian Federation
2Department of Faculty Surgery, Irkutsk State Medical University, Irkutsk, Russian Federation
Objective: Study the proteolytic activity during experimental peritonitis using Seroguard® as a local anti-inflammatory agent
Methods: The experiment involved male Wistar rats aged 6 months. The researchers induced experimental peritonitis in the animals using a specific technique they developed. In the control group (n=20), the rats were given an intraperitoneal injection of 3 ml of saline one day after simulating peritonitis. The experimental group (n=19) received the same volume of the Seroguard® solution (JSC Pharmasyntez, Russia), a prolonged form of the p38 MAPK inhibitor. Healthy age-matched rats (n=7) are used to determine indicators typical for intact animals. Total protein and low molecular weight proteins (LMWP) in liver homogenates were determined using the modified Lowry protein assay, and serum total protein and albumin were measured using kits purchased from BioSystems S.A. (Costa Brava, Spain)
Results: The experimental peritonitis significantly impacted the levels of LMWP in the liver tissue. A statistically significant increase in their accumulation in the group with purulent peritonitis was observed when Seroguard® was not administered throughout the study period. However, a single administration of the Seroguard® reduced the severity of proteolytic reactions in peritonitis. Additionally, Seroguard® led to a temporary inhibition of albumin synthesis by hepatocytes for up to 3 days, followed by compensation by the 7th day of observation
Conclusion: Diffuse purulent peritonitis is characterized by significant activation of proteolytic processes and the accumulation of proteolysis products in the liver. Seroguard® inhibited the increase in proteolysis activity. When administered as a single injection into the abdominal cavity on the first day of simulating a purulent inflammatory process, this effect is more noticeable in the initial stages of observation. Reducing the production of proteolysis products may play a significant role in therapy to decrease the risk of developing multiorgan failure in peritonitis. However, the observed decrease in albumin production in the initial days after drug administration in the settings of extensive peritoneal damage should be a focus of clinical studies to assess the safety of the drug in this pathology
Keywords: Peritonitis, p38 MAPK inhibitor, proteolysis, low molecular weight proteins.
References
- Gelfand BR (red.), Kirienko AI (red.), Khachatryan NN (red.) Abdominal'naya khirurgicheskaya infektsiya: Rossiyskie natsional'nye rekomendatsii. 2-e izdanie, pererabotannoe i dopolnennoe [Abdominal surgical infection: Russian national recommendations. 2nd edition, revised and expanded]. Moscow, RF: OOO «Meditsinskoe informatsionnoe agentstvo»; 2018. 168 p.
- Ayushinova NI, Shurygina IA, Shurygin MG, Grigoriev EG. Gospital'naya epidemiologiya spaechnoy bolezni bryushnoy polosti [Hospital epidemiology of abdominal adhesive disease]. Byulleten' Vostochno-Sibirskogo nauchnogo tsentra Sibirskogo otdeleniya Rossiyskoy akademii meditsinskikh nauk. 2016;1(4):115- 8.
- Liao S, Lin Y, Liu L, Yang S, Lin Y, He J, Shao Y. ADAM10-a "multitasker" in sepsis: Focus on its posttranslational target. Inflamm Res. 2023;72(3):395-423. https://doi.org/10.1007/s00011-022-01673-0
- Van Opdenbosch N, Lamkanfi M. Caspases in cell death, inflammation, and disease. Immunity. 2019;50(6):1352-64. https://doi.org/10.1016/j.immuni.2019.05.020
- Rao S, Grover M. Intestinal proteases. Curr Opin Gastroenterol. 2023;39(6):472- 8. https://doi.org/10.1097/MOG.0000000000000972
- Kokhanov AV, Kchibekov EA, Lutseva OA, Musagaliev AA. Urovni syvorotochnogo ferritina i termostabil'noy fraktsii al'bumina v krovi u bol'nykh appendikulyarnym peritonitom [Levels of serum ferritin and thermostable fraction of albumin in the blood in patients with appendiceal peritonitis]. Sovremennye problemy nauki i obrazovaniya. 2016;6:78.
- Nesterova IV, Kolesnikova NV, Chudilova GA, Lomtatidze LV, Kovalyova SV, Evglevskiy AA. Neytrofil'nye granulotsity: novyy vzglyad na starykh «igrokov» na immunologicheskom pole [Neutrophil granulocytes: A new look at old “players” in the immunological field]. Immunologiya. 2015;36(4):257-65.
- Bond JS. Proteases: History, discovery, and roles in health and disease. J Biol Chem. 2019;294(5):1643-51. https://doi.org/10.1074/jbc.TM118.004156
- Newton K, Dixit VM, Nobuhiko K. Dying cells fan the flames of inflammation. Science. 2021;374(6571):1076-80. https://doi.org/10.1126/science.abi5934
- Zhang X, Liu H, Hashimoto K, Yuan S, Zhang J. The gut-liver axis in sepsis: Interaction mechanisms and therapeutic potential. Crit Care. 2022;26(1):213. https://doi.org/10.1186/s13054-022-04090-1
- Shurygina I, Trukhan I, Dremina N, Shurygin M. Mitogen-activated protein kinases as a target for regulating the connective tissue growth. Advances in health and disease. New York, USA; 2023. p. 99-122.
- Zhang HW, Ding JD, Zhang ZS, Zhao SS, Duan KY, Zhu BQ, et al. Critical role of p38 in spinal cord injury by regulating inflammation and apoptosis in a rat model. Spine. 2020;45(7):E355-E363. https://doi.org/10.1097/ BRS.0000000000003282
- Shurygina IA, Shurygin MG, Chepurnykh EE. Sposob lecheniya enteral'noy nedostatochnosti pri vospalitel'nykh i travmaticheskikh povrezhdeniyakh bryushiny [Method for treating enteral insufficiency in inflammatory and traumatic injuries of the peritoneum]. Patent Rossiyskoy Federatsii № 2749435. 10.06.2021.
- Krylov N, Rybin V. Spayki v bryushnoy polosti: sushchestvuyut li effektivnye metody ikh profilaktiki [Adhesions in the abdominal cavity: are there effective methods for their prevention]? Vrach. 2014;11:2-5.
- Chepurnykh EE, Shurygina IA, Fadeeva TV, Grigorшev EG. Sposob modelirovani-ya peritonit [Method for modeling peritonitis]. Patent Rossiyskoy Аederatsii № 2716482. 11.03.2020.
- diZerega GS. Peritoneum, peritoneal healing and adhesion formation. In: diZerega GS. (eds.) Peritoneal surgery. Berlin-Heidelberg-New York: Springer; 2006. p. 3-38.
- Pestel S, Beltz HW, Claar P, Lind H, Mischnik M, Raquet E, et al. FVIII half-life extension by coadministration of a D'D3 albumin fusion protein in mice, rabbits, rats, and monkeys. Blood Adv. 2020;4(9):1870-80. https://doi.org/10.1182/ bloodadvances.2019000999
- Dumitrescu G, Januszkiewicz A, Agren A, Magnusson M, Sparrelid E, Rooyackers O, Wernerman J. Fibrinogen and albumin synthesis rates in major upper abdominal surgery. PLoS One. 2022;17(10):e0276775. https://doi.org/10.1371/ journal.pone.0276775
- Solass W, Horvath P, Struller F, Königsrainer I, Beckert S, Königsrainer A, et al. Functional vascular anatomy of the peritoneum in health and disease. Pleura Peritoneum. 2016;1(3):145-58. https://doi.org/10.1515/pp-2016-0015
- Shurygina IA, Shurygin MG, Ayushinova NI, Granina GB, Zelenin NV. Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase. Frontiers of Chemical Science and Engineering. 2012;6(2):232-7.
- Sanz-Ezquerro JJ, Cuenda A. p38 signalling pathway. Int J Mol Sci. 2021;22(3):1003. https://doi.org/10.3390/ijms22031003
- Canovas B, Nebreda AR. Diversity and versatility of p38 kinase signalling in health and disease. Nat Rev Mol Cell Biol. 2021;22(5):346-66. https://doi. org/10.1038/s41580-020-00322-w
- Shurygina IA, Ayushinova NI, Rodionova LV, Chepurnykh EE, Shurygin MG. Izuchenie gepatotoksichnosti i nefrotoksichnosti novogo protivospaechnogo preparata (eksperimental'noe issledovanie) [Study of hepatotoxicity and nephrotoxicity of a new anti-adhesion drug (experimental study)]. Acta Biomedica Scientifica. 2017;2(3):92-6. https://doi.org/10.12737/article_59f03600d074b4.31010834
- Fadeeva TV, Shurygina IA, Dremina NN, Vetokhina AV, Chepurnykh EE, Shurygin MG. Bakterial'naya translokatsiya pri eksperimental'nom peritonite [Bacterial translocation in experimental peritonitis]. Zabaykal'skiy meditsinskiy vestnik. 2019;4:128-33.
Authors' information:
Shurygin Mikhail Gennadievich,
Doctor of Medical Sciences, Head of the Scientific Laboratory Department, Irkutsk Scientific Centre of Surgery and Traumatology
Scopus ID: 36159014400
ORCID ID: 0000-0001-5921-0318
SPIN: 6638-5630
Author ID: 484911
E-mail: mshurygin@gmail.com
Bogorodskaya Svetlana Leonidovna,
Candidate of Biological Sciences, Researcher, Laboratory of Cell Pathophysiology and Biochemistry, Irkutsk Scientific Centre of Surgery and Traumatology
Researcher ID: JZK-6695-2024
Scopus ID: 25651703400
ORCID ID: 0000-0002-2471-4230
SPIN: 1457-6856
Author ID: 635889
E-mail: sbogorodskaya@mail.ru
Chepurnykh Elena Evgenievna,
Candidate of Medical Sciences, Academic Secretary, Irkutsk Scientific Centre of Surgery and Traumatology; Associate Professor at the Department of Faculty Surgery, Irkutsk State Medical University
Scopus ID: 57221861398
ORCID ID: 0000-0002-3197-4276
SPIN: 6020-9356
Author ID: 220736
E-mail: chepurnikh.ee@yandex.ru
Rodionova Lyubov Viktorovna,
Candidate of Biological Sciences, Head of the Laboratory of Cell Pathophysiology and Biochemistry, Irkutsk Scientific Centre of Surgery and Traumatology
Researcher ID: S-3053-2016
Scopus ID: 57219936626
ORCID ID: 0000-0002-5080-9225
SPIN: 7467-1670
Author ID: 92385
E-mail: greidmacho@yandex.ru
Samoylova Liliya Grigorievna,
Junior Researcher, Laboratory of Cell Pathophysiology and Biochemistry, Irkutsk Scientific Centre of Surgery and Traumatology
Scopus ID: 57221874558
ORCID ID: 0000-0003-4482-6130
SPIN: 9380-2988
Author ID: 693413
E-mail: popovalg@mail.ru
Shurygina Irina Aleksandrovna,
Doctor of Medical Sciences, Full Professor, Deputy Director for Science, Irkutsk Scientific Centre of Surgery and Traumatology
Researcher ID: B-4059-2018
Scopus ID: 36244455300
ORCID ID: 0000-0003-3980-050X
SPIN: 6745-5426
Author ID: 161435
E-mail: irinashurygina@gmail.com
Information about support in the form of grants, equipment, medications
The research was carried out in accordance with the research plan of Irkutsk Scientific Centre of Surgery and Traumatology «Study of the pathogenesis of the reparative process and development of methods of influencing the pathological process in surgical and traumatological pathology» (state registration number – 122022200212-6). The authors did not receive financial support from manufacturers of medicines and medical equipment
Conflicts of interest: No conflict
Address for correspondence:
Bogorodskaya Svetlana Leonidovna
Candidate of Biological Sciences, Researcher, Laboratory of Cell Pathophysiology and Biochemistry, Irkutsk Scientific Centre of Surgery and Traumatology
664003, Russian Federation, Irkutsk, Bortsov Revolyutsii str., 1, post office box 12
Tel.: +7 (3952) 290336
E-mail: sbogorodskaya@mail.ru
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