Severity of polymicrobial sepsis modulates mitochondrial function in rat liver

Herminghaus, Anna; Barthel, Franziska; Heinen, André; Beck, Christopher; Vollmer, Christian; Bauer, Inge; Weidinger, Adelheid; Козлов, А. В.; Picker, O.

doi:10.1016/j.mito.2015.08.001

Cited by 13 publications

(15 citation statements)

References 26 publications

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“…Polymicrobial abdominal infection was induced by the implantation of a 14-G stent into the wall of the large intestine to promote faecal leakage into the abdominal cavity (colon ascendens stent peritonitis surgery (CASP)) as previously reported [18, 25].…”

Section: Methodsmentioning

confidence: 99%

“…Multiple studies on hepatic mitochondrial function in sepsis failed to reach a consensus and are therefore controversial [12]. Following septic injury, studies have demonstrated impaired [13–15], unaffected [16, 17, 21], or even improved mitochondrial function [18–20]. Whereas studies on hepatic mitochondria are numerous, studies on mitochondrial function of other organs are lacking.…”

Section: Introductionmentioning

confidence: 99%

“…Even if the colon is not the primary focus of infection, inflammation could be worsened when the barrier function is damaged [23]. We have previously shown that hepatic mitochondrial function depends on the severity of sepsis [18]. Operative stress induced by laparotomy and, to a greater extent, moderate sepsis led to a higher energy coupling within 24 h without affecting the efficacy of oxidative phosphorylation, whereas more severe sepsis did not affect hepatic mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

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Time-related changes in hepatic and colonic mitochondrial oxygen consumption after abdominal infection in rats

Herminghaus

Papenbrock

Eberhardt

et al. 2019

ICMx

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BackgroundEvidence suggests that early adaptive responses of hepatic mitochondria occur in experimentally induced sepsis. Little is known about both colonic mitochondrial function during abdominal infection and long-term changes in mitochondrial function under inflammatory conditions. We hypothesize that hepatic and colonic mitochondrial oxygen consumption changes time-dependently after sterile laparotomy and in the course of abdominal infection. The aim of the present study was to investigate the hepatic and colonic mitochondrial respiration after sterile laparotomy and abdominal infection over up to 96 h.MethodsAfter approval of the local Animal Care and Use Committee, 95 Wistar rats were randomized into 8 groups (n = 11–12): 1–4 sham (laparotomy only) and 5–8 colon ascendens stent peritonitis (CASP). Healthy, unoperated animals served as controls (n = 9). The mitochondrial respiration in colon and liver homogenates was assessed 24, 48, 72, and 96 h after surgery. Mitochondrial oxygen consumption was determined using a Clark-type electrode. State 2 (oxygen consumption in the presence of the substrates for complexes I and II) and state 3 respiration (ADP dependent) were assessed. The respiratory control ratio (RCR state 3/state 2) and ADP/O ratio (ADP added/oxygen consumed) were calculated for both complexes. Data are presented as means ± SD, two-way ANOVA followed by Tukey’s post hoc test.ResultsHepatic RCR was initially (after 24 h) elevated in both operated groups; after 48 h only, the septic group was elevated compared to controls. In CASP groups, the hepatic ADP/O ratio for complex I was elevated after 24 h (vs. controls) and after 48 h (vs. sham) but declined after 72 h (vs. controls). The ADP/O ratio for complex II stayed unchanged over the time period until 96 h.The colonic RCR and ADP/O did not change over time after sham or CASP operation.ConclusionHepatic, but not colonic, mitochondrial respiration is increased in the initial phase (until 48 h) and normalizes in the longer course of time (until 96 h) of abdominal infection.Electronic supplementary materialThe online version of this article (10.1186/s40635-018-0219-9) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Time-related changes in hepatic and colonic mitochondrial oxygen consumption after abdominal infection in rats

Herminghaus

Papenbrock

Eberhardt

et al. 2019

ICMx

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“…Pilot studies indicate that different degrees of sepsis severity and MOSF differently influence the mitochondrial function, intracellular, and extracellular heat shock protein (HSP) concentrations, resistin and adiponectin hormone levels, and thiobarbituric acid‐reactant substances (TBARS), a product of lipid peroxidation, as an index of oxidative stress. Also heme metabolism is affected in sepsis and SIRS .…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino‐Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children

Spanaki

Tavladaki

Dimitriou

et al. 2018

J Parenter Enteral Nutr

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“…10b) in the CLP model. Possibly, polymicrobial sepsis resulted in hypoxic hepatitis [24][25][26]. Under this pathophysiological condition, enzymatic dysfunctions of cytochrome p4502R-1 might fail to hydroxylate the inactive form of vitamin D3 into its intermediate form (i.e., 25-hydroxyvitamin D3) in the liver [27,28].…”

Section: Effects Of Inactive and Active Forms Of Vd3 On Clpinduced Pomentioning

confidence: 99%

Cathelicidin preserves intestinal barrier function in polymicrobial sepsis

Chan

Liang

et al. 2020

Crit Care

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Objectives: The intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.Design: To examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp +/+ ) and knockout (Cnlp −/− ) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model. Results: The ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.Conclusions: Endogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis.

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Severity of polymicrobial sepsis modulates mitochondrial function in rat liver

Cited by 13 publications

References 26 publications

Time-related changes in hepatic and colonic mitochondrial oxygen consumption after abdominal infection in rats

Time-related changes in hepatic and colonic mitochondrial oxygen consumption after abdominal infection in rats

Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino‐Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children

Cathelicidin preserves intestinal barrier function in polymicrobial sepsis

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