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

Yuri Yu. Borshchev , Sarkis M. Minasyan , Inessa Yu. Burovenko , Egor S. Protsak , Victor Yu. Borshchev , Olga V. Borshcheva , Michael M. Galagudza

Medical academic journal ›› 2025, Vol. 25 ›› Issue (1) : 42 -53.

PDF
Medical academic journal ›› 2025, Vol. 25 ›› Issue (1) : 42 -53. DOI: 10.17816/MAJ635918
Original research
research-article

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

Author information +
History +
PDF

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.

Keywords

myocardium / ischemia-reperfusion / cardioprotection / systemic inflammatory response syndrome / cytokines / probiotics

Cite this article

Download citation ▾
Yuri Yu. Borshchev, Sarkis M. Minasyan, Inessa Yu. Burovenko, Egor S. Protsak, Victor Yu. Borshchev, Olga V. Borshcheva, Michael M. Galagudza. The effect of probiotic bacteria and pharmacological anti-inflammatory effects on the size of myocardial infarction in rats with systemic inflammation. Medical academic journal, 2025, 25(1): 42-53 DOI:10.17816/MAJ635918

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982–3021. doi: 10.1016/j.jacc.2020.11.010

[2]

Roth G.A., Mensah G.A., Johnson C.O., et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study // J Am Coll Cardiol. 2020. Vol. 76, N 25. P. 2982–3021. doi: 10.1016/j.jacc.2020.11.010

[3]

Nguyen TM, Melichova D, Aabel EW, et al. Mortality in patients with acute coronary syndrome—a prospective 5-year follow-up study. J Clin Med. 2023;12(20):6598. doi: 10.3390/jcm12206598

[4]

Nguyen T.M., Melichova D., Aabel E.W., et al. Mortality in patients with acute coronary syndrome—a prospective 5-year follow-up study // J Clin Med. 2023. Vol. 12, N 20. P. 6598. doi: 10.3390/jcm12206598

[5]

Byrne RA, Ndrepepa G, Braun S, et al. Peak cardiac troponin-T level, scintigraphic myocardial infarct size and one-year prognosis in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol. 2010;106(9):1212–1217. doi: 10.1016/j.amjcard.2010.06.050

[6]

Byrne R.A., Ndrepepa G., Braun S., et al. Peak cardiac troponin-T level, scintigraphic myocardial infarct size and one-year prognosis in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction // Am J Cardiol. 2010. Vol. 106, N 9. P. 1212–1217. doi: 10.1016/j.amjcard.2010.06.050

[7]

Heusch G. Cardioprotection and its translation: a need for new paradigms? Or for new pragmatism? An opinionated retro- and perspective. J Cardiovasc Pharmacol Ther. 2023;28:10742484231179613. doi: 10.1177/10742484231179613

[8]

Heusch G. Cardioprotection and its translation: a need for new paradigms? Or for new pragmatism? An opinionated retro- and perspective // J Cardiovasc Pharmacol Ther. 2023. Vol. 28. P. 10742484231179613. doi: 10.1177/10742484231179613

[9]

Borshchev YuYu, Sonin DL, Minasyan SM, et al. Effect of intestinal microbiota on myocardial resistance to ischemia-reperfusion injury. Siberian Journal of Clinical and Experimental Medicine. 2023;38(4):86–96. EDN: WSRUQF doi: 10.29001/2073-8552-2023-38-4-86-96

[10]

Галагудза М.М., Борщев Ю.Ю., Минасян С.М., и др. Влияние кишечной микробиоты на устойчивость миокарда к ишемическому-реперфузионному повреждению // Сибирский журнал клинической и экспериментальной медицины. 2023. Т. 38, № 4. С. 86–96. EDN: WSRUQF doi: 10.29001/2073-8552-2023-38-4-86-96

[11]

Borshchev YuY, Burovenko IY, Karaseva AB, et al. Probiotic therapy with Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis results in infarct size limitation in rats with obesity and chemically induced colitis. Microorganisms. 2022;10(11):2293. doi: 10.3390/microorganisms10112293

[12]

Borshchev Yu.Y., Burovenko I.Y., Karaseva A.B., et al. Probiotic therapy with Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis results in infarct size limitation in rats with obesity and chemically induced colitis // Microorganisms. 2022. Vol. 10, N 11. P. 2293. doi: 10.3390/microorganisms10112293

[13]

Borshchev YuYu, Minasean SM, Semenova NYu, et al. Effect of pro- and metabiotic Lactobacillus delbrueckii D5 strain on myocardial resistance to ischemia–reperfusion injury in the rat model of systemic inflammatory response. Bulletin of Siberian Medicine. 2024;23(2):28–36. EDN: XKTFOC doi: 10.20538/1682-0363-2024-2-28-36

[14]

Борщев Ю.Ю., Минасян С.М., Семенова Н.Ю., и др. Влияние про- и метабиотической формы штамма Lactobacillus delbrueckii D5 на устойчивость миокарда к ишемии–реперфузии в условиях системного воспалительного ответа у крыс // Бюллетень сибирской медицины. 2024. Т. 23, № 2. С. 28–36. EDN: XKTFOC doi: 10.20538/1682-0363-2024-2-28-36

[15]

Gan XT, Ettinger G, Huang CX, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7(3):491–499. doi: 10.1161/CIRCHEARTFAILURE.113.000978

[16]

Gan X.T., Ettinger G., Huang C.X., et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat // Circ Heart Fail. 2014. Vol. 7, N 3. P. 491–499. doi: 10.1161/CIRCHEARTFAILURE.113.000978

[17]

Lam V, Su J, Hsu A, et al. Intestinal microbial metabolites are linked to severity of myocardial infarction in rats. PLoS One. 2016;11(8):e0160840. doi: 10.1371/journal.pone.0160840

[18]

Lam V., Su J., Hsu A., et al. Intestinal microbial metabolites are linked to severity of myocardial infarction in rats // PLoS One. 2016. Vol. 11, N 8. P. e0160840. doi: 10.1371/journal.pone.0160840

[19]

Borshchev YuYu, Sonin DL, Burovenko IYu, et al. The effect of probiotic strains on myocardial infarction size, biochemical and immunological parameters in rats with systemic inflammatory response syndrome and polymorbidity. J Evol Biochem Physiol. 2022;58(6):2058–2069. doi: 10.1134/s0022093022060321

[20]

Borshchev Yu.Yu., Sonin D.L., Burovenko I.Yu., et al. The effect of probiotic strains on myocardial infarction size, biochemical and immunological parameters in rats with systemic inflammatory response syndrome and polymorbidity // J Evol Biochem Physiol. 2022. Vol. 58, N 6. P. 2058–2069. doi: 10.1134/s0022093022060321

[21]

Danilo CA, Constantopoulos E, McKee LA, et al. Bifidobacterium animalis subsp. lactis 420 mitigates the pathological impact of myocardial infarction in the mouse. Benef Microbes. 2017;8(2):257–269. doi: 10.3920/BM2016.0119

[22]

Danilo C.A., Constantopoulos E., McKee L.A., et al. Bifidobacterium animalis subsp. lactis 420 mitigates the pathological impact of myocardial infarction in the mouse // Benef Microbes. 2017. Vol. 8, N 2. P. 257–269. doi: 10.3920/BM2016.0119

[23]

Borschev YuYu, Burovenko IYu, Karaseva AB, et al. Modeling of systemic inflammatory response syndrome by chemical induction of colon injury in rats. Medical Immunology (Russia). 2020;22(1): 87–98. EDN: PQHSUW doi: 10.15789/1563-0625-MOS-1839

[24]

Борщев Ю.Ю., Буровенко И.Ю., Карасева А.Б., и др. Моделирование синдрома системной воспалительной реакции химической индукцией травмы толстого кишечника у крыс // Медицинская иммунология. 2020. Т. 22, № 1. С. 87–98. EDN: PQHSUW doi: 10.15789/1563-0625-MOS-1839

[25]

Vallejo S, Palacios E, Romacho T, et al. The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats. Cardiovasc Diabetol. 2014;13:158. doi: 10.1186/s12933-014-0158-z

[26]

Vallejo S., Palacios E., Romacho T., et al. The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats // Cardiovasc Diabetol. 2014. Vol. 13. P. 158. doi: 10.1186/s12933-014-0158-z

[27]

Diogo LN, Faustino IV, Afonso RA, et al. Voluntary oral administration of losartan in rats. J Am Assoc Lab Anim Sci. 2015;54(5):549–556.

[28]

Diogo L.N., Faustino I.V., Afonso R.A., et al. Voluntary oral administration of losartan in rats // J Am Assoc Lab Anim Sci. 2015. Vol. 54, N 5. P. 549–556.

[29]

Bae HW, Lee N, Seong GJ, et al. Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia. BMC Ophthalmol. 2016;6:75. doi: 10.1186/s12886-016-0262-9

[30]

Bae H.W., Lee N., Seong G.J., et al. Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia // BMC Ophthalmol. 2016. Vol. 6. P. 75. doi: 10.1186/s12886-016-0262-9

[31]

Garcia-Olmo D, Payá J, Lucas FJ, García-Olmo DC. The effects of the pharmacological manipulation of postoperative intestinal motility on colonic anastomoses. An experimental study in a rat model. Int J Colorectal Dis. 1997;12(2):73–77. doi: 10.1007/s003840050084

[32]

Garcia-Olmo D., Payá J., Lucas F.J., García-Olmo D.C. The effects of the pharmacological manipulation of postoperative intestinal motility on colonic anastomoses. An experimental study in a rat model // Int J Colorectal Dis. 1997. Vol. 12, N 2. P. 73–77. doi: 10.1007/s003840050084

[33]

Retter AS, Frishman WH. The role of tumor necrosis factor in cardiac disease. Heart Dis. 2001;3(5):319–25. doi: 10.1097/00132580-200109000-00008

[34]

Retter A.S., Frishman W.H. The role of tumor necrosis factor in cardiac disease // Heart Dis. 2001. Vol. 3, N 5. P. 319–25. doi: 10.1097/00132580-200109000-00008

[35]

Hanna A, Frangogiannis NG. Inflammatory cytokines and chemokines as therapeutic targets in heart failure. Cardiovasc Drugs Ther. 2020;34(6):849–863. doi: 10.1007/s10557-020-07071-0

[36]

Hanna A., Frangogiannis N.G. Inflammatory cytokines and chemokines as therapeutic targets in heart failure // Cardiovasc Drugs Ther. 2020. Vol. 34, N 6. P. 849–863. doi: 10.1007/s10557-020-07071-0

[37]

Mami W, Znaidi-Marzouki S, Doghri R, et al. Inflammatory bowel disease increases the severity of myocardial infarction after acute ischemia-reperfusion injury in mice. Biomedicines. 2023;11(11):2945. doi: 10.3390/biomedicines11112945

[38]

Mami W., Znaidi-Marzouki S., Doghri R., et al. Inflammatory bowel disease increases the severity of myocardial infarction after acute ischemia-reperfusion injury in mice // Biomedicines. 2023. Vol. 11, N 11. P. 2945. doi: 10.3390/biomedicines11112945

[39]

Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M. Free fatty acid receptors in health and disease. Physiol Rev. 2020;100(1):171–210. doi: 10.1152/physrev.00041.2018

[40]

Kimura I., Ichimura A., Ohue-Kitano R., Igarashi M. Free fatty acid receptors in health and disease // Physiol Rev. 2020. Vol. 100, N 1. P. 171–210. doi: 10.1152/physrev.00041.2018

[41]

Zhao J, Zhang Q, Cheng W, et al. Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia / reperfusion. Cardiovasc Res. 2023;119(6):1390–1402. doi: 10.1093/cvr/cvad023

[42]

Zhao J., Zhang Q., Cheng W., et al. Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia / reperfusion // Cardiovasc Res. 2023. Vol. 119, N 6. P. 1390–1402. doi: 10.1093/cvr/cvad023

[43]

Zhu J, Huang J, Dai D, et al. Recombinant human interleukin-1 receptor antagonist treatment protects rats from myocardial ischemia-reperfusion injury. Biomed Pharmacother. 2019;111:1–5. doi: 10.1016/j.biopha.2018.12.031

[44]

Zhu J., Huang J., Dai D., et al. Recombinant human interleukin-1 receptor antagonist treatment protects rats from myocardial ischemia-reperfusion injury // Biomed Pharmacother. 2019. Vol. 111. P. 1–5. doi: 10.1016/j.biopha.2018.12.031

[45]

Toldo S, Schatz AM, Mezzaroma E, et al. Recombinant human interleukin-1 receptor antagonist provides cardioprotection during myocardial ischemia reperfusion in the mouse. Cardiovasc Drugs Ther. 2012;26(3):273–276. doi: 10.1007/s10557-012-6389-x

[46]

Toldo S., Schatz A.M., Mezzaroma E., et al. Recombinant human interleukin-1 receptor antagonist provides cardioprotection during myocardial ischemia reperfusion in the mouse // Cardiovasc Drugs Ther. 2012. Vol. 26, N 3. P. 273–276. doi: 10.1007/s10557-012-6389-x

[47]

Yu X, Patterson E, Huang S, et al. Tumor necrosis factor alpha, rapid ventricular tachyarrhythmias, and infarct size in canine models of myocardial infarction. J Cardiovasc Pharmacol. 2005;45(2):153–159. doi: 10.1097/01.fjc.0000151930.12026.b7

[48]

Yu X., Patterson E., Huang S., et al. Tumor necrosis factor alpha, rapid ventricular tachyarrhythmias, and infarct size in canine models of myocardial infarction // J Cardiovasc Pharmacol. 2005. Vol. 45, N 2. P. 153–159. doi: 10.1097/01.fjc.0000151930.12026.b7

[49]

Belosjorow S, Bolle I, Duschin A, et al. TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits. Am J Physiol Heart Circ Physiol. 2003;284(3):H927–930. doi: 10.1152/ajpheart.00374.2002

[50]

Belosjorow S., Bolle I., Duschin A., et al. TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits // Am J Physiol Heart Circ Physiol. 2003. Vol. 284, N 3. P. H927–930. doi: 10.1152/ajpheart.00374.2002

[51]

Jong WM, Ten Cate H, Linnenbank AC, et al. Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model. Inflamm Res. 2016;65(6):489–499. doi: 10.1007/s00011-016-0931-4

[52]

Jong W.M., Ten Cate H., Linnenbank A.C., et al. Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model // Inflamm Res. 2016. Vol. 65, N 6. P. 489–499. doi: 10.1007/s00011-016-0931-4

[53]

Lecour S, Rochette L, Opie L. Free radicals trigger TNF alpha-induced cardioprotection. Cardiovasc Res. 2005;65(1):239–243. doi: 10.1016/j.cardiores.2004.10.003

[54]

Lecour S., Rochette L., Opie L. Free radicals trigger TNF alpha-induced cardioprotection // Cardiovasc Res. 2005. Vol. 65, N 1. P. 239–243. doi: 10.1016/j.cardiores.2004.10.003

[55]

Parlakpinar H, Ozer MK, Acet A. Effects of captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion induced infarct size. Cytokine. 2011;56(3):688–694. doi: 10.1016/j.cyto.2011.09.002

[56]

Parlakpinar H., Ozer M.K., Acet A. Effects of captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion induced infarct size // Cytokine. 2011. Vol. 56, N 3. P. 688–694. doi: 10.1016/j.cyto.2011.09.002

[57]

Preckel B, Schlack W, Gonzàlez M, et al. Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog heart. Basic Res Cardiol. 2000;95(5):404–412. doi: 10.1007/s003950070040

[58]

Preckel B., Schlack W., Gonzàlez M., et al. Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog heart // Basic Res Cardiol. 2000. Vol. 95, N 5. P. 404–412. doi: 10.1007/s003950070040

[59]

Ford WR, Clanachan AS, Hiley CR, Jugdutt BI. Angiotensin II reduces infarct size and has no effect on post-ischaemic contractile dysfunction in isolated rat hearts. Br J Pharmacol. 2001;134(1):38–45. doi: 10.1038/sj.bjp.0704225

[60]

Ford W.R., Clanachan A.S., Hiley C.R., Jugdutt B.I. Angiotensin II reduces infarct size and has no effect on post-ischaemic contractile dysfunction in isolated rat hearts // Br J Pharmacol. 2001. Vol. 134, N 1. P. 38–45. doi: 10.1038/sj.bjp.0704225

[61]

Halder N, Lal G. Cholinergic system and its therapeutic importance in inflammation and autoimmunity. Front Immunol. 2021;12:660342. doi: 10.3389/fimmu.2021.660342

[62]

Halder N., Lal G. Cholinergic system and its therapeutic importance in inflammation and autoimmunity // Front Immunol. 2021. Vol. 12. P. 660342. doi: 10.3389/fimmu.2021.660342

[63]

Pan Z, Guo Y, Qi H, et al. M3 subtype of muscarinic acetylcholine receptor promotes cardioprotection via the suppression of miR-376b-5p. PLoS One. 2012;7(3):e32571. doi: 10.1371/journal.pone.0032571

[64]

Pan Z., Guo Y., Qi H., et al. M3 subtype of muscarinic acetylcholine receptor promotes cardioprotection via the suppression of miR-376b-5p // PLoS One. 2012. Vol. 7, N 3. P. e32571. doi: 10.1371/journal.pone.0032571

[65]

Dolejší E, Janoušková A, Jakubík J. Muscarinic receptors in cardioprotection and vascular tone regulation. Physiol Res. 2024;73(Suppl 1):S389–S400. doi: 10.33549/physiolres.935270

[66]

Dolejší E., Janoušková A., Jakubík J. Muscarinic receptors in cardioprotection and vascular tone regulation // Physiol Res. 2024. Vol. 73, N Suppl 1. P. S389–S400. doi: 10.33549/physiolres.935270

RIGHTS & PERMISSIONS

Eco-Vector

AI Summary AI Mindmap
PDF

103

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/