Alterations in mitochondrial respiration and reactive oxygen species in patients poisoned with carbon monoxide treated with hyperbaric oxygen

Jang, David H.; Khatri, Utsha G.; Shortal, Brenna P.; Kelly, Matthew; Hardy, Kevin R.; Lambert, David S; Eckmann, David M.

doi:10.1186/s40635-018-0169-2

Cited by 26 publications

(29 citation statements)

References 34 publications

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“…We then showed that CO-induced CcO inhibition is partially reversed by treatment Ngb-H64Q-CCC (FIGURE 6). While alterations in complexes I and II have not classically been associated with CO poisoning, decreases in complex I and II activity were recently reported in the peripheral blood mononuclear cells of acutely CO poisoned patients (75)(76)(77). This was similar to our observation of complex activities in heart homogenate from our in vivo CO exposure model.…”

Section: Reversal Of Co-induced Mitochondrial Poisoningsupporting

confidence: 92%

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide–induced mitochondrial poisoning

Rose

Bocian

et al. 2020

Journal of Biological Chemistry

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Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

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Section: Reversal Of Co-induced Mitochondrial Poisoningsupporting

confidence: 92%

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide–induced mitochondrial poisoning

Rose

Bocian

et al. 2020

Journal of Biological Chemistry

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“…In the CO group, mitochondrial respiration was significantly lower at key respiratory states that includes complex IV or cytochrome c oxidase respiration with a resultant decrease in other key respiratory states such as Max respiration and uncoupled CI respiration. The finding that CO results in a decrease in CIV respiration with a decrease in other complex activity is a consistent finding in our previous work as well as others [12,25,34,35]. There were no differences in other respiratory states such as uncoupled CII which is most likely related to our sample size where a larger sample size may detect a significant difference [12,25,34,35].…”

Section: Flowchart Of Peripheral Blood Mononuclear Cell (Pbmc) Isolatsupporting

confidence: 91%

“…We performed a specialized protocol to establish the respiratory capacities at various complexes providing more detailed respiratory activity at complex (C) I, II, III, IV. Our published manuscripts describe these methods in further detail in regard to injections with specific concentrations [12,25,28].…”

Section: Mitochondrial Bioenergetics and Dynamics Methodsmentioning

confidence: 99%

“…The mitochondria play a central role in cellular metabolism where oxygen consumption through the electron transport system (ETS) is tightly coupled to ATP production and regulated by metabolic demands [11]. The mitochondria are also involved in a variety of important cellular processes that include heat dissipation, production of ROS, and regulation of ion gradients which can be measured with the simultaneous measurement of respirometry and select fluorophores demonstrated with our prior work [12].…”

Section: Introductionmentioning

confidence: 96%

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Translational Application of Measuring Mitochondrial Functions in Blood Cells Obtained from Patients with Acute Poisoning

et al. 2018

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It is conservatively estimated that 5,000 deaths per year and 20,000 injuries in the USA are due to poisonings caused by chemical exposures (e.g., carbon monoxide, cyanide, hydrogen sulfide, phosphides) that are cellular inhibitors. These chemical agents result in mitochondrial inhibition resulting in cardiac arrest and/or shock. These cellular inhibitors have multi-organ effects, but cardiovascular collapse is the primary cause of death marked by hypotension, lactic acidosis, and cardiac arrest. The mitochondria play a central role in cellular metabolism where oxygen consumption through the electron transport system is tightly coupled to ATP production and regulated by metabolic demands. There has been increasing use of human blood cells such as peripheral blood mononuclear cells and platelets, as surrogate markers of mitochondrial function in organs due to acute care illnesses. We demonstrate the clinical applicability of measuring mitochondrial bioenergetic and dynamic function in blood cells obtained from patients with acute poisoning using carbon monoxide poisoning as an illustration of our technique. Our methods have potential application to guide therapy and gauge severity of disease in poisoning related to cellular inhibitors of public health concern.

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“…•− (Fukai and Ushio-Fukai 2011). It has been well documented that ROS production increases in HBO conditions, although oxidative susceptibility varies with the cell type, parameters of HBO therapy and number of exposures (Jang et al 2018, Simsek et al 2011. Literature data on SOD activity in HBO-treated subjects frequently document its increase going either in parallel with elevated ROS production and markers of oxidative stress (Simsek et al 2011) or fully compensating for oxidative damage (Sun et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts

Dejmek

Kohoutová²,

Kripnerová³

et al. 2018

Physiol Res

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Hyperbaric oxygen (HBO) therapy, i.e. breathing pure oxygen under increased environmental pressures serves as a treatment for diverse medical conditions. However, elevated oxygen concentration can be detrimental to central nervous system or lungs. Our study aimed to evaluate the effects of repeated exposure to HBO on mitochondrial respiration assessed by high-resolution respirometry (HRR), cell viability estimated by PrestoBlue® reaction, morphology analyzed by routine phase contrast and fluorescent microscopy, and superoxide dismutase (SOD) and citrate synthase (CS) activities using human lung fibroblasts. The cells were exposed to HBO for 2 h per day for 5 consecutive days. One day after the last exposure, HBO cells displayed significantly smaller area and perimeter, compromised viability and elevated SOD activity. No changes were detected in CS activity or quality of mitochondrial network. HRR revealed impaired mitochondrial oxygen consumption manifested by increased leak respiration, decreased activity of complex II and compromised ATP-related oxygen consumption when fatty acids were oxidized. Our findings document that in conditions mimicking chronic intermittent exposure to HBO, lung fibroblasts suffer from compromised mitochondrial respiration linked to complex II and impaired cellular growth in spite of increased antioxidant defense. Underlying mechanism of this HBO-induced mitochondrial dysfunction should be further explored.

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Alterations in mitochondrial respiration and reactive oxygen species in patients poisoned with carbon monoxide treated with hyperbaric oxygen

Cited by 26 publications

References 34 publications

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide–induced mitochondrial poisoning

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide–induced mitochondrial poisoning

Translational Application of Measuring Mitochondrial Functions in Blood Cells Obtained from Patients with Acute Poisoning

Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts

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