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Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis

INTRODUCTION: In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H(2)S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefor...

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Autores principales: Schulz, Jan, Kramer, Sandra, Kanatli, Yasin, Kuebart, Anne, Bauer, Inge, Picker, Olaf, Vollmer, Christian, Truse, Richard, Herminghaus, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215355/
https://www.ncbi.nlm.nih.gov/pubmed/34163476
http://dx.doi.org/10.3389/fimmu.2021.671935
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author Schulz, Jan
Kramer, Sandra
Kanatli, Yasin
Kuebart, Anne
Bauer, Inge
Picker, Olaf
Vollmer, Christian
Truse, Richard
Herminghaus, Anna
author_facet Schulz, Jan
Kramer, Sandra
Kanatli, Yasin
Kuebart, Anne
Bauer, Inge
Picker, Olaf
Vollmer, Christian
Truse, Richard
Herminghaus, Anna
author_sort Schulz, Jan
collection PubMed
description INTRODUCTION: In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H(2)S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H(2)S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis. METHODS: In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg(-1) i.p., 2: glibenclamide (GL) 5 mg • kg(-1) i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO(2)) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn’s multiple comparison test (mitochondria). p < 0.05 was considered significant. RESULTS: STS increased µHbO(2) (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO(2) and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO(2) and µflow (µHbO(2) 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO(2) and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO(2) or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered. CONCLUSION: The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.
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spelling pubmed-82153552021-06-22 Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis Schulz, Jan Kramer, Sandra Kanatli, Yasin Kuebart, Anne Bauer, Inge Picker, Olaf Vollmer, Christian Truse, Richard Herminghaus, Anna Front Immunol Immunology INTRODUCTION: In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H(2)S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H(2)S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis. METHODS: In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg(-1) i.p., 2: glibenclamide (GL) 5 mg • kg(-1) i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO(2)) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn’s multiple comparison test (mitochondria). p < 0.05 was considered significant. RESULTS: STS increased µHbO(2) (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO(2) and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO(2) and µflow (µHbO(2) 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO(2) and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO(2) or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered. CONCLUSION: The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8215355/ /pubmed/34163476 http://dx.doi.org/10.3389/fimmu.2021.671935 Text en Copyright © 2021 Schulz, Kramer, Kanatli, Kuebart, Bauer, Picker, Vollmer, Truse and Herminghaus https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Schulz, Jan
Kramer, Sandra
Kanatli, Yasin
Kuebart, Anne
Bauer, Inge
Picker, Olaf
Vollmer, Christian
Truse, Richard
Herminghaus, Anna
Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title_full Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title_fullStr Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title_full_unstemmed Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title_short Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
title_sort sodium thiosulfate improves intestinal and hepatic microcirculation without affecting mitochondrial function in experimental sepsis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215355/
https://www.ncbi.nlm.nih.gov/pubmed/34163476
http://dx.doi.org/10.3389/fimmu.2021.671935
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