Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study

Tang

2021

Sci Rep

We investigated the impact of aerobic exercise (AE) on multiple organ dysfunction syndrome (MODS), aortic injury, pathoglycemia, and death during sepsis. ICR mice were randomized into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Mice were trained with low-intensity for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ morphology and damage. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, and bronchoalveolar lavage fluid (BALF) cell count, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, serum insulin levels, plasma high-mobility group box 1 (HMGB1) levels, glucose transporter 1 (Glut1) and HMGB1, silent information regulator 1 (Sirt-1), and nuclear factor erythroid 2-related factor 2 (Nrf-2) mRNA expression levels in lung tissue. AE improved sepsis-associated multiple organ dysfunction syndrome (MODS), aortic injury, hypoglycemia, and death. AE prominently decreased pulmonary inflammation, pulmonary edema, and modulated redox balance during sepsis. AE prominently decreased neutrophil content in organ. AE prominently downregulated CXCL-1, CXCL-8, IL-6, TNF-α, Glu1, and HMGB1 mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung during sepsis. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels and serum insulin levels during sepsis. A 4-week AE improves sepsis-associated MODS, aortic injury, pathoglycemia, and death. AE impairs LPS-induced lactate and HMGB1 release partly because AE increases serum insulin levels and decreases the levels of Glut1. AE is a novel therapeutic strategy for sepsis targeting aerobic glycolysis.

Section: Introductionmentioning

confidence: 99%

Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice

Tang

2021

Sci Rep

“…Previous studies have found that the oxidant/antioxidant balance played a prominent role in the pathogenesis of sepsis and LPS administration led to oxidative stress injury [5]. In the present study, we identified the antioxidant effects of exercise.…”

Section: Discussionmentioning

confidence: 73%

“…Sepsis, which has many complications, such as MODS, hypotension, and hypoglycemia, exhibits a high mortality rate stemming from a systemic infection that involves alterations in inflammatory parameters and oxidative status [1][2][3]. The pathogenesis of sepsis is complex and inflammation and oxidative stress play critical roles in the pathogenesis of sepsis [4,5]. Sepsis is characterized by an uncontrolled inflammatory response involving inflammatory mediators, including IL-1RN, IL-6, IL-10, and TNF-α, and effector cells, among which neutrophils play a key role [6,7].…”

Section: Introductionmentioning

confidence: 99%

Aerobic Exercise Improves Sepsis via Impairing LPS-induced Lactate and HMGB1 Release in Mice

Tang

2021

Preprint

Purpose: In the present study, we attempted to investigate whether aerobic exercise (AE) could prevent sepsis and its complications and explored the related mechanisms. Methods: Forty ICR mice were divided into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Ex and Ex + LPS mice were performed with low-intensity AE for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ injury. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, and plasma high-mobility group box 1 (HMGB1) levels, and bronchoalveolar lavage fluid (BALF) cell count. Sixty mice were used to perform survival rate analysis. Results: AE improved survival rates, MODS, and aortic injury in mice with sepsis. AE decreased LPS-induced oxidative stress injury in lung tissue. AE reduced the infiltration of neutrophils in the lung, liver, kidney, and heart tissues. AE suppressed CXCL-1, CXCL-8, IL-6, and TNF-α mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels during sepsis. Conclusions: AE improves sepsis-associated lung, liver, kidney, heart, and aortic injury and death. AE modulates the inflammatory-anti-inflammatory and oxidative-antioxidative balance in the lung. AE, which can regulate the Warburg effect and impair LPS-induced lactate and HMGB1 release, is a novel therapeutic strategy for sepsis targeting aerobic glycolysis.

“…Oxidative stress has been implicated in the pathogenesis of sepsis [36, 37]. Taurine can enhance the ability of the antioxidant defence system by protecting antioxidant enzymes [38].…”

Section: Discussionmentioning

confidence: 99%

Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A ¹H NMR-Based Metabolomics Analysis

Zheng

Mediators of Inflammation

et al. 2019

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.