Emerging cellular-based therapies in carbon monoxide poisoning.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1563 (Electronic) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE

Original Publication: Bethesda, Md. : American Physiological Society,

Cell- and Tissue-Based Therapy*/methods; Carbon Monoxide/*toxicity ; Carbon Monoxide Poisoning/*drug therapy ; Succinic Acid/*pharmacology; Animals ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Prodrugs/pharmacology

Carbon monoxide (CO) is an odorless and colorless gas with multiple sources that include engine exhaust, faulty furnaces, and other sources of incomplete combustion of carbon compounds such as house fires. The most serious complications for survivors of consequential CO exposure are persistent neurological sequelae occurring in up to 50% of patients. CO inhibits mitochondrial respiration by specifically binding to the heme a 3 in the active site of CIV-like hydrogen sulfide, cyanide, and phosphides. Although hyperbaric oxygen remains the cornerstone for treatment, it has variable efficacy requiring new approaches to treatment. There is a paucity of cellular-based therapies in the area of CO poisoning, and there have been recent advancements that include antioxidants and a mitochondrial substrate prodrug. The succinate prodrugs derived from chemical modification of succinate are endeavored to enhance delivery of succinate to cells, increasing uptake of succinate into the mitochondria, and providing metabolic support for cells. The therapeutic intervention of succinate prodrugs is thus potentially applicable to patients with CO poisoning via metabolic support for fuel oxidation and possibly improving efficacy of HBO therapy.

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R21ES031243 HHS | NIH | National Institute of Environmental Health Sciences (NIEHS); R01 HL141386 United States HL NHLBI NIH HHS; R01HL141386 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R03 HL154232 United States HL NHLBI NIH HHS; P30 ES013508 United States ES NIEHS NIH HHS; K08 HL136858 United States HL NHLBI NIH HHS; R03HL154232 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R21 ES031243 United States ES NIEHS NIH HHS; K08HL136858 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)

Keywords: carbon monoxide; cellular therapies; mitochondria; respiration; succinate prodrug

0 (Prodrugs)
7U1EE4V452 (Carbon Monoxide)
AB6MNQ6J6L (Succinic Acid)

Date Created: 20210616 Date Completed: 20210922 Latest Revision: 20220802

20231215

PMC8424679

10.1152/ajpcell.00022.2021

34133239