Differential inhibition of mitochondrial respiratory complexes by inhalation of combustion smoke and carbon monoxide, in vivo, in the rat brain

Heung M. Lee, Lance M. Hallberg, George H. Greeley, Ella Englander

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Combustion smoke contains gases and particulates, which act via hypoxia and cytotoxicity producing mechanisms to injure cells and tissues. While carbon monoxide (CO) is the major toxicant in smoke, its toxicity is exacerbated in the presence of other compounds. Here, we examined modulations of mitochondrial and cytosolic energy metabolism by inhalation of combustion smoke versus CO, in vivo, in the rat brain. Measurements revealed reduced activities of respiratory chain (RC) complexes, with greater inhibition by smoke than equivalent CO in ambient air. In the case of RC complex IV, inhibition by CO and smoke was similarsuggesting that complex IV inhibition is primarily by the action of CO. In contrast, inhibition of complexes I and III was greater by smoke. Increases in cytosolic lactate dehydrogenase and pyruvate kinase activities accompanied inhibition of RC complexes, likely reflecting compensatory increases in cytosolic energy production. Together, the data provide new insights into the mechanisms of smoke inhalation-induced perturbations of brain energetics, which impact neuronal function and contribute to the development of neuropathologies in survivors of exposures to CO and combustion smoke.

Original languageEnglish (US)
Pages (from-to)770-777
Number of pages8
JournalInhalation Toxicology
Volume22
Issue number9
DOIs
StatePublished - 2010

Fingerprint

Carbon Monoxide
Smoke
Inhalation
Rats
Brain
Electron Transport
Pyruvate Kinase
Cytotoxicity
L-Lactate Dehydrogenase
Energy Metabolism
Toxicity
Gases
Air
Modulation
Tissue

Keywords

  • Brain
  • carbon monoxide
  • combustion smoke
  • energetics
  • mitochondria
  • respiratory chain complexes

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Differential inhibition of mitochondrial respiratory complexes by inhalation of combustion smoke and carbon monoxide, in vivo, in the rat brain. / Lee, Heung M.; Hallberg, Lance M.; Greeley, George H.; Englander, Ella.

In: Inhalation Toxicology, Vol. 22, No. 9, 2010, p. 770-777.

Research output: Contribution to journalArticle

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