title: The effectiveness of oxygen therapy in carbon monoxide poisoning is pressure- and time-dependent: a study on cultured astrocytes.
abstract: Carbon monoxide (CO) poisoning causes neuronal and glial apoptosis that can result in delayed neurological symptoms. The damage of brain cells can be prevented by oxygen therapy. Based on the central role of astrocytes in maintaining neuronal function and viability we investigated the toxic effects of 3000ppm CO in air followed by 24h of normoxia and evaluated the possible protective influence of 100% normobaric oxygen or 100% oxygen at a pressure of 3bar (hyperbaric) against CO poisoning in these cells. CO/normoxia caused a progressive decline of viability, increase in reactive oxygen species and decline of mitochondrial membrane potential and intracellular ATP levels in cultured rat astrocytes. Increased caspase-9, caspase-8 and calpain activity converged in activation of caspase-3/7. 1h treatment with oxygen disclosed pressure- and time-dependent efficacy in restoring astrocytic mitochondrial function and the prevention of apoptosis. The protective effect was most evident when the astrocytes were exposed to hyperbaric oxygen, but not normobaric oxygen, 1-5h after exposure to CO.
authors.affiliation: Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, Ljubljana, Slovenia. Electronic address: damijana-mojca.juric@mf.uni-lj.si.
authors.forename: Damijana M
authors.initials: DM
authors.lastname: Jurič
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, Ljubljana, Slovenia. Electronic address: finderle@mf.uni-lj.si.
authors.forename: Žarko
authors.initials: Ž
authors.lastname: Finderle
authors.affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, Ljubljana, Slovenia. Electronic address: dusan.suput@mf.uni-lj.si.
authors.forename: Dušan
authors.initials: D
authors.lastname: Šuput
authors.affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, Ljubljana, Slovenia; Poison Control Centre, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, Ljubljana, Slovenia. Electronic address: miran.brvar@kclj.si.
authors.forename: Miran
authors.initials: M
authors.lastname: Brvar
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D002249:Carbon Monoxide Poisoning / Q000628:therapy*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D006931:Hyperbaric Oxygenation; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D009457:Neuroglia; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002154:Calpain; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: Apoptosis; Astrocytes; Carbon monoxide; Hyperbaric oxygen; Normobaric oxygen