The effect of probiotic bacteria and pharmacological anti-inflammatory effects on the size of myocardial infarction in rats with systemic inflammation

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Abstract

BACKGROUND: In recent years, it has been shown that certain probiotics have a cardioprotective effect in conditions of comorbidity and systemic inflammation. The mechanisms of probiotic-mediated cardioprotection have not been studied in practice. There is an assumption that the heart attack-limiting effect of probiotics is mediated by their anti-inflammatory effect.

AIM: To study the severity of the cardioprotective effect of a mixture of probiotic strains of Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) in rats with systemic inflammatory response syndrome in comparison with the use of IL-1 receptor blockers, AT1 angiotensin II receptors, M-cholinergic receptors, as well as an inhibitor of tumor necrosis factor alfa binding to its receptors.

METHODS: The experiments were performed on male Wistar stock rats on a model of systemic inflammatory response syndrome. The rats of the corresponding groups, after chemical induction of a systemic inflammatory response, were intragastrically injected with probiotic strains, losartan and hyoscine butyl bromide; subcutaneously — etanercept and anakinra for 8 days. The assessment of myocardial resistance to ischemic-reperfusion injury was carried out on the model of global ischemia-reperfusion of an isolated heart at an upgraded Langendorff facility, by planimetric estimation of the size of the necrosis zone. The concentration of cytokines in blood plasma was assessed by enzyme immunoassay.

RESULTS: The size of the myocardial necrosis zone in the systemic inflammatory response group, rats with systemic inflammatory response syndrome, was significantly higher than in the control group — 45% (38; 48)% and 30% (26; 31)% (p < 0.05). In the groups of probiotic strains, anakinra and losartan, the size of the necrosis zone was 32% (28; 35)%, 26% (24; 35)% and 30% (25; 36)%, which is less than in the systemic inflammatory response group (p < 0.05). In the etanercept and hyoscine butyl bromide groups, the size of the necrosis zone was 35% (26; 36)% and 42% (32; 46)%, not significantly different from the SIR group (p > 0.05). Hemodynamic parameters of the isolated heart did not differ between the groups. In the systemic inflammatory response group, the concentration of proinflammatory cytokines and transforming growth factor beta in blood plasma was significantly higher than in the control group. At the same time, in the groups of probiotic strains, anakinra, losartan and hyoscine butyl bromide, a significant decrease in the levels of certain cytokines was noted, confirming the presence of an anti-inflammatory effect.

CONCLUSION: The introduction of probiotics to rats with systemic inflammatory response syndrome caused a decrease in the size of the necrosis zone. At the same time, the blockade of tumor necrosis factor alfa binding to receptors and the blockade of M-cholinergic receptors were not accompanied by a decrease in size of the necrosis zone in this model. Pharmacological blockade of the IL-1 and AT1 angiotensin II receptors had a cardioprotective and anti-inflammatory effect similar to the probiotic strains group, which indicates the unidirectional effect of the tested effects.

About the authors

Yuri Yu. Borshchev

Almazov National Medical Research Center; Petrov National Medical Research Center of Oncology

Email: niscon@mail.ru
ORCID iD: 0000-0003-3096-9747
SPIN-code: 3454-4113

Сand. Sci. (Biology), Head of the Toxicology Department of the Institute of Experimental Medicine; Researcher at the Laboratory of Cancer Chemoprophylaxis and Oncopharmacology

Russian Federation, Saint Petersburg; Saint Petersburg

Sarkis M. Minasyan

Almazov National Medical Research Center; Academician Pavlov First Saint Petersburg State Medical University

Email: carkis@ya.ru
ORCID iD: 0000-0001-6382-5286
SPIN-code: 5241-8875

MD, Cand. Sci. (Medicine), Senior Researcher at the Laboratory of Myocardial Microcirculation of the Institute of Experimental Medicine; Researcher at the Department of Pathophysiology

Russian Federation, Saint Petersburg; Saint Petersburg

Inessa Yu. Burovenko

Almazov National Medical Research Center

Email: burovenko.inessa@gmail.com
ORCID iD: 0000-0001-6637-3633
SPIN-code: 2112-1480

Junior Researcher at the Toxicology Department of the Institute of Experimental Medicine

Russian Federation, Saint Petersburg

Egor S. Protsak

Almazov National Medical Research Center

Email: egor-protsak@yandex.ru
ORCID iD: 0000-0002-9217-9890
SPIN-code: 8762-0486

Junior Researcher at the Toxicology Department of the Institute of Experimental Medicine

Russian Federation, Saint Petersburg

Victor Yu. Borshchev

Academician Pavlov First Saint Petersburg State Medical University

Email: frapsodindva@gmail.com
ORCID iD: 0009-0002-6943-0159
SPIN-code: 1933-6545

Student

Russian Federation, Saint Petersburg

Olga V. Borshcheva

Almazov National Medical Research Center

Author for correspondence.
Email: violga27@mail.ru
ORCID iD: 0009-0007-6131-3085
SPIN-code: 7532-5404

Researcher at the Toxicology Department of the Institute of Experimental Medicine

Russian Federation, Saint Petersburg

Michael M. Galagudza

Almazov National Medical Research Center; Academician I.P. Pavlov First Saint Petersburg State Medical University; Institute for Analytical Instrumentation of the Russian Academy of Sciences

Email: galagudza@almazovcentre.ru
ORCID iD: 0000-0001-5129-9944
SPIN-code: 2485-4176

MD, Dr. Sci. (Medicine), Corresponding Member and Professor of the RAS, Director of the Institute of Experimental Medicine; Professor at the Department of Pathophysiology; Chief Researcher

Russian Federation, Saint Petersburg; Saint Petersburg; Saint Petersburg

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2. Fig. 1. The size of the myocardial necrosis zone by group. Groups: CON, Control; SIR, systemic inflammatory response syndrome (SIRS); PRK, SIRS and a mixture of LA-5 and BB-12; ANA, SIRS and anakinra; LOZ, SIRS and losartan; ETA, SIRS and eternacept; GSB, SIRS and hyoscine butyl bromide. * p < 0.05 in relation to the CON group; # p < 0.05 in relation to the SIR group.

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