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

<h4>Background</h4>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 i...

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Main Authors: Yury Yu Borshchev, Sarkis M Minasian, Inessa Yu Burovenko, Victor Yu Borshchev, Egor S Protsak, Natalia Yu Semenova, Olga V Borshcheva, Michael M Galagudza
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0225185
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author Yury Yu Borshchev
Sarkis M Minasian
Inessa Yu Burovenko
Victor Yu Borshchev
Egor S Protsak
Natalia Yu Semenova
Olga V Borshcheva
Michael M Galagudza
author_facet Yury Yu Borshchev
Sarkis M Minasian
Inessa Yu Burovenko
Victor Yu Borshchev
Egor S Protsak
Natalia Yu Semenova
Olga V Borshcheva
Michael M Galagudza
author_sort Yury Yu Borshchev
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
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spelling doaj.art-2a06bf2e61ad4b42ae4008f809a674d62022-12-21T18:27:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011411e022518510.1371/journal.pone.0225185Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.Yury Yu BorshchevSarkis M MinasianInessa Yu BurovenkoVictor Yu BorshchevEgor S ProtsakNatalia Yu SemenovaOlga V BorshchevaMichael M Galagudza<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0225185
spellingShingle Yury Yu Borshchev
Sarkis M Minasian
Inessa Yu Burovenko
Victor Yu Borshchev
Egor S Protsak
Natalia Yu Semenova
Olga V Borshcheva
Michael M Galagudza
Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
PLoS ONE
title Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
title_full Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
title_fullStr Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
title_full_unstemmed Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
title_short Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis.
title_sort effects of tetracycline on myocardial infarct size in obese rats with chemically induced colitis
url https://doi.org/10.1371/journal.pone.0225185
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