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Preliminary Research : Application of Non-Invasive Measure of Cytochrome c Oxidase Redox States and Mitochondrial Function in a Porcine Model of Carbon Monoxide Poisoning

Lewis, Alistair T. ; Forti, Rodrigo M. ; Alomaja, Oladunni ; Mesaros, Clementina ; Piel, Sarah LU orcid ; Greenwood, John C. ; Talebi, Fatima M. ; Mavroudis, Constantine D. ; Kelly, Matthew and Kao, Shih Han , et al. (2022) In Journal of Medical Toxicology 18(3). p.214-222
Abstract

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology. Methods: Four pigs (10 kg) were divided into two groups: Sham (n = 2) and CO (n = 2).... (More)

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology. Methods: Four pigs (10 kg) were divided into two groups: Sham (n = 2) and CO (n = 2). Administration of a dose of CO at 2000 ppm to the CO group over 120 minutes followed by 30 minutes of re-oxygenation at room air. The control group received room air for 150 minutes. Non-invasive optical monitoring was used to measure CIV redox states. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. At the end of the exposure, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Snap frozen cortical tissue was also used for ATP concentrations and western blotting. Results: While a preliminary ongoing study, animals in the CO group showed possible early decreases in brain mitochondrial respiration, citrate synthase density, CIV redox changes measured with optics, and an increase in the lactate-to-pyruvate ratio. Conclusions: There is a possible observable phenotype highlighting the important role of mitochondrial function in the injury of CO poisoning.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Basic science, Biomarker, Carbon monoxide, Mitochondria, Optics
in
Journal of Medical Toxicology
volume
18
issue
3
pages
9 pages
publisher
Springer
external identifiers
  • scopus:85129077915
  • pmid:35482181
ISSN
1556-9039
DOI
10.1007/s13181-022-00892-5
project
Mitochondrial dysfunction in drug and chemical toxicity: mechanism, target identification and therapeutic development
language
English
LU publication?
yes
id
74eb92c1-0362-4b82-a838-449c9a795c38
date added to LUP
2022-07-05 12:58:14
date last changed
2024-06-11 19:42:51
@article{74eb92c1-0362-4b82-a838-449c9a795c38,
  abstract     = {{<p>Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology. Methods: Four pigs (10 kg) were divided into two groups: Sham (n = 2) and CO (n = 2). Administration of a dose of CO at 2000 ppm to the CO group over 120 minutes followed by 30 minutes of re-oxygenation at room air. The control group received room air for 150 minutes. Non-invasive optical monitoring was used to measure CIV redox states. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. At the end of the exposure, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Snap frozen cortical tissue was also used for ATP concentrations and western blotting. Results: While a preliminary ongoing study, animals in the CO group showed possible early decreases in brain mitochondrial respiration, citrate synthase density, CIV redox changes measured with optics, and an increase in the lactate-to-pyruvate ratio. Conclusions: There is a possible observable phenotype highlighting the important role of mitochondrial function in the injury of CO poisoning.</p>}},
  author       = {{Lewis, Alistair T. and Forti, Rodrigo M. and Alomaja, Oladunni and Mesaros, Clementina and Piel, Sarah and Greenwood, John C. and Talebi, Fatima M. and Mavroudis, Constantine D. and Kelly, Matthew and Kao, Shih Han and Shofer, Frances S. and Ehinger, Johannes K. and Kilbaugh, Todd J. and Baker, Wesley B. and Jang, David H.}},
  issn         = {{1556-9039}},
  keywords     = {{Basic science; Biomarker; Carbon monoxide; Mitochondria; Optics}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{214--222}},
  publisher    = {{Springer}},
  series       = {{Journal of Medical Toxicology}},
  title        = {{Preliminary Research : Application of Non-Invasive Measure of Cytochrome c Oxidase Redox States and Mitochondrial Function in a Porcine Model of Carbon Monoxide Poisoning}},
  url          = {{http://dx.doi.org/10.1007/s13181-022-00892-5}},
  doi          = {{10.1007/s13181-022-00892-5}},
  volume       = {{18}},
  year         = {{2022}},
}