Cytochrome c limits oxidative stress and decreases acidosis in a rat model of hemorrhagic shock and reperfusion injury

Powell, Rebecca D.; Goodenow, Donna; Mixer, Hannah V.; McKillop, Iain H.; Evans, Susan

doi:10.1097/ta.0000000000001257

Cited by 11 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eight healthy BALB/c mice were randomly selected as group N ( n = 8). The rest animals were subjected to the establishment of HS model by cardiac puncture as previously described 7 . Twenty-seven mice were successfully modeled.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Antishock Characteristics of Erythrocyte-mediated Endoplasmic Reticulum Stress in Macrophages in Severe Hemorrhagic Shock Environment Based on TLR9-cGAS-STING-IFN Signal Axis

Kang

Yuan

et al. 2020

Cell Transplant

View full text Add to dashboard Cite

This study aimed to investigate the protective effects of erythrocyte-mediated endoplasmic reticulum (ER) stress in macrophages in hemorrhagic shock. An hemorrhagic shock model was established in male BALB/c mice. Animals were randomly divided into three groups ( n = 8): control group (A), erythrocyte reinfusion group (B), and TLR9 inhibition group (C). Eight healthy BALB/c mice were also included as group N ( n = 8). Mice in group A were not treated, while mice in groups B and C were transfused with red blood cells separated from the blood of mice in group N. Flow cytometry was used to detect the expression of erythrocyte surface protein TLR9 in each group. Immunofluorescence assay was used to analyze the distribution and relative expression of protein STING in macrophages. Flow cytometry was used to analyze the expression of STING, ATF6, and IRE1 in macrophages. Enzyme-linked immunosorbent assay was used to analyze the levels of inflammatory signal molecules, including IFN-α, IFN-β, IL-6, CCL4, CCL5, and IL-6. FITC-Annexin V was used to analyze the apoptosis of immune cells (macrophages) in mouse blood samples and to detect the concentration of calcium ions in erythrocyte cytoplasm. The results showed that the expression of erythrocyte surface protein TLR9; the distribution of STING-positive cells in macrophages; the expressions of STING, ATF6, and IRE1 in macrophages; the levels of inflammatory signal molecules; the apoptosis rate of macrophages; and the intracellular calcium concentration in erythrocytes in group B were higher than those in group A, followed by group C. These results suggest that TLR9 regulates ER stress in macrophages of mice with hemorrhagic shock through the TLR9-cGAS-STING-IFN signaling pathway. Increased expression of TLR9 enhanced macrophage activity, reduced apoptosis, enhanced inflammatory response and immune response, and restored electrolyte level, which might be a therapeutic option for the treatment of hemorrhagic shock.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Flow cytometry was performed in triplicate. (7) The intracytoplasmic calcium concentration in erythrocytes was detected using fluo-3 fluorescence labeling and flow cytometry. Venous blood samples (2 ml) were collected and centrifuged for 10 min at room temperature of 1,000 r/min.…”

Section: Measurementsmentioning

confidence: 99%

Antishock Characteristics of Erythrocyte-mediated Endoplasmic Reticulum Stress in Macrophages in Severe Hemorrhagic Shock Environment Based on TLR9-cGAS-STING-IFN Signal Axis

Kang

Yuan

et al. 2020

Cell Transplant

View full text Add to dashboard Cite

show abstract

“…16 This ROS tsunami can exhaust the endogenous antioxidant mechanisms, leaving the reperfused tissues vulnerable to mitochondrial permeability transition, lipid peroxidation, protein carbonylation and oxidation, and DNA damage. 14,15 Consequently, excessive ROS contribute to cell death and organ failure following hemorrhagic injury.…”

Section: Impact Statementmentioning

confidence: 99%

“…14 Basal physiological production of reactive oxygen species (ROS) is readily managed by endogenous antioxidant enzymes and cofactors. 15 However, severe blood loss, the resultant ischemia of under-perfused tissues, and tissue reperfusion effected by resuscitation, provoke massive ROS overproduction. 16 This ROS tsunami can exhaust the endogenous antioxidant mechanisms, leaving the reperfused tissues vulnerable to mitochondrial permeability transition, lipid peroxidation, protein carbonylation and oxidation, and DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults

Park

Kay

Sprick

et al. 2019

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 ± 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO2) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F2-isoprostanes (F2-IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Δ) in SV, ranged from 27 to 74% (53.5 ± 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 ± 2.6% ( P < 0.001 vs. pre-LBNP baseline). F2-IsoP increased by 28.5 ± 11.6% ( P = 0.05) from baseline (24 ± 2 pg/mL) to presyncope (29 ± 3 pg/mL). The increase in F2-IsoP was not associated with %Δ SV ( r = 0.21, P = 0.46), %Δ MAP ( r = 0.05, P = 0.86), %Δ SmO2 ( r = 0.05, P = 0.90), or the maximum level of LBNP attained ( r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress. Impact statement We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

show abstract

“…Moreover, during hemorrhagic shock, oxidative stress from vascular NOX may cause endothelial dysfunction, leading to platelet activation, increased vascular permeability, and loss of vasoreactivity . Therapies that either provide antioxidants or enhance endogenous antioxidant systems have been shown to decrease free radical damage and improve organ function following HSR …”

Section: Resveratrol and Oxidative Stressmentioning

confidence: 99%

The grapes and wrath: using resveratrol to treat the pathophysiology of hemorrhagic shock

Sims

Baur

2017

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Resveratrol, a naturally occurring polyphenol found in grapes, has been shown to reduce oxidative stress and inflammation in a variety of conditions. Recently, resveratrol has been investigated as a potential adjunct to resuscitation therapy for hemorrhagic shock-a condition characterized by tissue hypoxia, mitochondrial dysfunction, and inflammation. Although standard resuscitation restores tissue perfusion, it can exacerbate oxidative stress and organ damage. In rodent models of severe hemorrhagic shock, resveratrol mitigates reperfusion injury, preserves organ function, and improves survival. While many of these benefits can be attributed to its ability to activate sirtuin 1, resveratrol interacts with many targets that are relevant to ischemia-reperfusion. Here, we explore the probable mechanisms, potential benefits, and possible problems associated with administering resveratrol as an adjunct during resuscitation of hemorrhagic shock.

show abstract

Cytochrome c limits oxidative stress and decreases acidosis in a rat model of hemorrhagic shock and reperfusion injury

Abstract: These studies demonstrate that cyt c reduces markers of physiologic stress, decreases oxidative stress, and lowers levels of circulating mtDNA. The impact of cytochrome c is organ specific. Further studies remain to determine the sum of the effects of cytochrome c on overall outcome.

Cited by 11 publications

References 33 publications

Antishock Characteristics of Erythrocyte-mediated Endoplasmic Reticulum Stress in Macrophages in Severe Hemorrhagic Shock Environment Based on TLR9-cGAS-STING-IFN Signal Axis

Antishock Characteristics of Erythrocyte-mediated Endoplasmic Reticulum Stress in Macrophages in Severe Hemorrhagic Shock Environment Based on TLR9-cGAS-STING-IFN Signal Axis

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults

The grapes and wrath: using resveratrol to treat the pathophysiology of hemorrhagic shock

Contact Info

Product

Resources

About