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: 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

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