#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis


Autoři: Yury Yu Borshchev aff001;  Sarkis M. Minasian aff001;  Inessa Yu Burovenko aff002;  Victor Yu Borshchev aff005;  Egor S. Protsak aff001;  Natalia Yu Semenova aff001;  Olga V. Borshcheva aff001;  Michael M. Galagudza aff001
Působiště autorů: Institute of Experimental Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation aff001;  Scientific Research Center “Probiocode SP”, Moscow, Russian Federation aff002;  Department of Pathophysiology, Saint Petersburg Pavlov State Medical University, Saint Petersburg, Russian Federation aff003;  Department of Physiology and Sanocreatology, Shevchenko Transnistria State University, Tiraspol, Republic of Moldova aff004;  Department of Microelectronics and Biomedical Engineering, Technical University of Moldova, Chisinau, Republic of Moldova aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225185

Souhrn

Background

Recent evidence suggests that antibiotic-induced changes in the composition of intestinal microflora, as well as the systemic immunoendocrine effects that result from them, can modulate myocardial tolerance to ischemia-reperfusion injury. The aim of this study was to investigate the effects of tetracycline (TTC) on myocardial infarct size in the isolated hearts obtained from obese rats with chemically-induced colitis (CIC). The association between TTC-induced changes in infarct size and intestinal microbiome composition as well as plasma levels of cytokines and short-chain fatty acids (SCFAs) was also studied.

Methods

Obesity was induced in Wistar rats by feeding them a high-fat, high-carbohydrate diet for five weeks. A single rectal administration of 3% acetic acid (2 mL) to the rats resulted in CIC. Healthy rats as well as obese rats with CIC received TTC (15 mg daily for 3 days) via gavage. The rats were euthanized, after which isolated heart perfusion with simulated global ischemia and reperfusion was performed. Infarct size was determined histochemically. Lipopolysaccharide (LPS) and cytokine levels in plasma were measured by enzyme-linked immunosorbent assay, whereas SCFA levels in plasma were measured by gas chromatography/mass spectrometry. The intestinal microbiome was analyzed using reverse transcription polymerase chain reaction.

Results

The treatment with TTC resulted in significant infarct size limitation (50 ± 7 vs. 62 ± 4% for the control mice, p < 0.05) in the hearts from intact animals. However, infarct size was not different between the control rats and the obese rats with CIC. Furthermore, infarct size was significantly larger in TTC-treated obese rats with CIC than it was in the control animals (77 ± 5%, p < 0.05). The concentrations of proinflammatory cytokines and LPS in serum were elevated in the obese rats with CIC. Compared to the control rats, the rats with both obesity and CIC had lower counts of Lactobacillus and Bifidobacterium spp. but higher counts of Escherichia coli. The effects of TTC on infarct size were not associated with specific changes in SCFA levels.

Conclusions

TTC reduced infarct size in the healthy rats. However, this effect was reversed in the obese animals with CIC. Additionally, it was associated with specific changes in gut microbiota and significantly elevated levels of cytokines and LPS.

Klíčová slova:

Colitis – Cytokines – Gastrointestinal tract – Ischemia – Microbiome – Obesity – Reperfusion


Zdroje

1. Hoelzer K, Wong N, Thomas J, Talkington K, Jungman E, Coukell A. Antimicrobial drug use in food-producing animals and associated human health risks: what, and how strong, is the evidence? BMC Vet Res. 2017;13:211. doi: 10.1186/s12917-017-1131-3 28676125

2. Danner MC, Robertson A, Behrends V, Reiss J. Antibiotic pollution in surface fresh waters: occurrence and effects. Sci Total Environ. 2019;664:793–804. doi: 10.1016/j.scitotenv.2019.01.406 30763859

3. Gorelik E, Masarwa R, Perlman A, Rotshild V, Abbasi M, Muszkat M, et al. Fluoroquinolones and cardiovascular risk: a systematic review, meta-analysis and network meta-analysis. Drug Saf. 2019;42:529–38. doi: 10.1007/s40264-018-0751-2 30368737

4. Zhang M, Xie M, Li S, Gao Y, Xue S, Huang H, et al. Electrophysiologic studies on the risks and potential mechanism underlying the proarrhythmic nature of azithromycin. Cardiovasc Toxicol. 2017;17:434–40. doi: 10.1007/s12012-017-9401-7 28213753

5. Corremans R, Adao R, De Keulenaer GW, Leite-Moreira AF, Bras-Silva C. Update on pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. Clin Exp Pharmacol Physiol. 2019;46:204–15. doi: 10.1111/1440-1681.13036 30244497

6. Stover KR, Farley JM, Kyle PB, Cleary JD. Cardiac toxicity of some echinocandin antifungals. Expert Opin Drug Saf. 2014;13:5–14. doi: 10.1517/14740338.2013.829036 24047086

7. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26: 1727–35. doi: 10.1096/fj.11-197921 22247331

8. Lam V, Su J, Hsu A, Gross GJ, Salzman NH, Baker JE. Intestinal microbial metabolites are linked to severity of myocardial infarction in rats. PLoS ONE 2016;11:e0160840. doi: 10.1371/journal.pone.0160840 27505423

9. Kagawa N, Senbonmatsu TA, Satoh K, Ichihara K, Yamagata N, Hatano O, et al. Tetracycline protects myocardium against ischemic injury. Front Biosci. 2005;10:608–19. doi: 10.2741/1557 15569603

10. Thind GS, Agrawal PR, Hirsh B, Saravolatz L, Chen-Scarabelli C, Narula J, et al. Mechanisms of myocardial ischemia-reperfusion injury and the cytoprotective role of minocycline: scope and limitations. Future Cardiol. 2015;11:61–76. doi: 10.2217/fca.14.76 25606703

11. Li Y, Li T, Qi H, Yuan F. Minocycline protects against hepatic ischemia/reperfusion injury in a rat model. Biomed Rep. 2015;3:19–24. doi: 10.3892/br.2014.381 25469240

12. Naderi Y, Sabetkasaei M, Parvardeh S, Zanjani TM. Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat. Brain Res Bull. 2017;131:207–13. doi: 10.1016/j.brainresbull.2017.04.010 28454931

13. Al-Darraji A, Haydar D, Chelvarajan L, Tripathi H, Levitan B, Gao E, et al. Azithromycin therapy reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction: potential therapeutic targets in ischemic heart disease. PLoS One. 2018;13:e0200474. doi: 10.1371/journal.pone.0200474 30001416

14. Heusch G. Critical issues for the translation of cardioprotection. Circ Res. 2017;120:1477–86. doi: 10.1161/CIRCRESAHA.117.310820 28450365

15. Collins KH, Hart DA, Seerattan RA, Reimer RA, Herzog W. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res. 2018;7:274–81. doi: 10.1302/2046-3758.74.BJR-2017-0201.R2 29922445

16. El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed Pharmacother. 2019;111:841–51. doi: 10.1016/j.biopha.2019.01.001 30616083

17. Minasian SM, Galagudza MM, Dmitriev YV, Kurapeev DI, Vlasov TD. Myocardial protection against global ischemia with Krebs-Henseleit buffer-based cardioplegic solution. J Cardiothorac Surg. 2013;8:60. doi: 10.1186/1749-8090-8-60 23547937

18. Romero-Perez D, Fricovsky E, Yamasaki KG Griffin M, Barraza-Hidalgo M, Dillmann W, et al. Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection. J Am Coll Cardiol. 2008;52:1086–94. doi: 10.1016/j.jacc.2008.06.028 18848143

19. Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem. 2005;94:819–27. doi: 10.1111/j.1471-4159.2005.03219.x 16033424

20. Lee SM, Yune TY, Kim SJ, Kim YC, Oh YJ, Markelonis GJ et al. Minocycline inhibits apoptotic cell death via attenuation of TNF-alpha expression following iNOS/NO induction by lipopolysaccharide in neuron/glia cocultures. J Neurochem. 2004;91:568–78. doi: 10.1111/j.1471-4159.2004.02780.x 15485488

21. Tao R, Kim SH, Honbo N, Karliner JS, Alano CC. Minocycline protects cardiac myocytes against simulated ischemia–reperfusion injury by inhibiting poly(ADPribose) polymerase-1. J Cardiovasc Pharmacol. 2010;56:659–68. doi: 10.1097/FJC.0b013e3181faeaf0 20881608

22. Scarabelli TM, Stephanou A, Pasini E, Gitti G, Townsend P, Lawrence K, et al. Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO. J Am Coll Cardiol. 2004;43:865–74. doi: 10.1016/j.jacc.2003.09.050 14998631

23. Cheung PY, Sawicki G, Wozniak M, Wang W, Radomski MW, Schulz R. Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation. 2000;101(15):1833–9. doi: 10.1161/01.cir.101.15.1833 10769285

24. Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R. Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev. 2014;66:1142–74. doi: 10.1124/pr.113.008300 25261534

25. Sack MN, Murphy E. The role of comorbidities in cardioprotection. J Cardiovasc Pharmacol Ther. 2011;16:267–72. doi: 10.1177/1074248411408313 21821527

26. Iliodromitis EK, Zoga A, Vrettou A, Andreadou I, Paraskevaidis IA, Kaklamanis L et al. The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits. Atherosclerosis. 2006;188:356–62. doi: 10.1016/j.atherosclerosis.2005.11.023 16376892

27. Przyklenk K, Maynard M, Greiner DL, Whittaker P. Cardioprotection with postconditioning: loss of efficacy in murine models of type-2 and type-1 diabetes. Antioxid Redox Signal. 2011;14:781–90. doi: 10.1089/ars.2010.3343 20578962

28. Hausenloy DJ, Garcia-Dorado D, Botker HE, Davidson SM, Downey J, Engel FB, et al. Novel targets and future strategies for acute cardioprotection: position paper of the European Society of Cardiology working group on cellular biology of the heart. Cardiovasc Res. 2017;113:564–85. doi: 10.1093/cvr/cvx049 28453734

29. Meng F, Li D, Song B, Li L. Impaired myocardial MIF/AMPK activation aggravates myocardial ischemia reperfusion injury in high-fat diet-induced obesity. Endocr Metab Immune Disord Drug Targets. 2019 Mar 26. doi: 10.2174/1871530319666190326143254 30914037

30. Salie R, Huisamen B, Lochner A. High carbohydrate and high fat diets protect the heart against ischaemia/reperfusion injury. Cardiovasc Diabetol. 2014;13:109. doi: 10.1186/s12933-014-0109-8 25197961

31. Inserte J, Aluja D, Barba I, Ruiz-Meana M, Miro E, Poncelas M, et al. High-fat diet improves tolerance to myocardial ischemia by delaying normalization of intracellular PH at reperfusion. J Mol Cell Cardiol. 2019;133:164–73. doi: 10.1016/j.yjmcc.2019.06.001 31194987

32. Behr C, Kamp H, Fabian E, Krennrich G, Mellert W, Peter E, et al. Gut microbiome-related metabolic changes in plasma of antibiotic-treated rats. Arch Toxicol. 2017;91:3439–54. doi: 10.1007/s00204-017-1949-2 28337503

33. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189–200. doi: 10.1080/19490976.2015.1134082 26963409

34. Mujico JR, Baccan GC, Gheorghe A, Diaz LE, Marcos A. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr. 2013;110:711–20. doi: 10.1017/S0007114512005612 23302605

35. Kain V, Van Der Pol W, Mariappan N, Ahmad A, Eipers P, Gibson DL, et al. Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure. FASEB J. 2019;33:6456–69. doi: 10.1096/fj.201802477R 30768364

36. Netto Candido TL, Bressan J, Alfenas RCG. Dysbiosis and metabolic endotoxemia induced by high-fat diet. Nutr Hosp. 2018;35:1432–40. doi: 10.20960/nh.1792 30525859

37. Sturgeon C, Lan J, Fasano A. Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model. Ann N Y Acad Sci. 2017;1397:130–42. doi: 10.1111/nyas.13343 28423466

38. Wu T, Jiang N, Ji Z, Shi G. The IRE1 signaling pathway is involved in the protective effect of low-dose LPS on myocardial ischemia-reperfusion injury. Life Sci. 2019 Jun 13. doi: 10.1016/j.lfs.2019.116569 31202841

39. Ha T, Hua F, Liu X, Ma J, McMullen JR, Shioi T, et al. Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovasc Res. 2008;78:546–53. doi: 10.1093/cvr/cvn037 18267957

40. Nader ND, Asgeri M, Davari-Farid S, Pourafkari L, Ahmadpour F, Porhomayon J, et al. The effect of lipopolysaccharide on ischemic-reperfusion injury of heart: a double hit model of myocardial ischemia and endotoxemia. J Cardiovasc Thorac Res. 2015;7:81–6. doi: 10.15171/jcvtr.2015.19 26430494

41. Hoshida S., Yamashita N., Otsu K., Hori M. Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats. J Am Coll Cardiol. 2002;40:826–31. doi: 10.1016/s0735-1097(02)02001-6 12204517

42. Hoshida S., Yamashita N., Otsu K., Hori M. The importance of manganese superoxide dismutase in delayed preconditioning: involvement of reactive oxygen species and cytokines. Cardiovasc Res. 2002;55:495–505. doi: 10.1016/s0008-6363(02)00337-1 12160946

43. Asgeri M, Pourafkari L, Kundra A, Javadzadegan H, Negargar S, Nader ND. Dual effects of tumor necrosis factor alpha on myocardial injury following prolonged hypoperfusion of the heart. Immunol Invest. 2015;44:23–35. doi: 10.3109/08820139.2014.921689 24949667


Článek vyšel v časopise

PLOS One


2019 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#