cytochrome-c-t and Carbon-Monoxide-Poisoning

The neurotoxic effects of carbon monoxide (CO) are well known. Brain hypoxia due to the binding of CO to hemoglobin is a recognized cause of CO neurotoxicity, while the direct effect of CO on intracellular targets remains poorly understood. In the present study, we have investigated the pathways leading to neural cell death induced by in vitro exposure to CO using a gas exposure chamber that we have developed. Mouse hippocampal neurons (HT22) and human glial cells (D384) were exposed to concentrations of CO ranging from 300 to 1000 ppm in the presence of 20% oxygen. Cytotoxicity was observed after 48 h exposure to 1000 ppm, corresponding to approximately 1 microM CO in the cultured medium, as measured by gas chromatography. CO induced cell death with characteristic features of apoptosis. Exposed cells exhibited loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, nuclei with chromatin condensation, and exposure of phosphatidyl serine on the external leaflet of the plasma membrane. CO also triggered activation of caspase and calpain proteases. Pre-incubation with either the pancaspase inhibitor Z-VAD-fmk (20 microM) or the calpain inhibitor E64d (25 microM) reduced by 50% the occurrence of apoptosis. When pre-incubating the cells with the two inhibitors together there was an additional reduction in the number of cells with apoptotic nuclei. These data suggest that CO causes apoptosis via activation of parallel proteolytic pathways involving both caspases and calpains. Furthermore, pre-treatment with the antioxidant MnTBAP (100 microM) significantly reduced the number of apoptotic nuclei, pointing to a critical role of oxidative stress in CO toxicity.

Topics: Animals; Annexin A5; Apoptosis; Calpain; Carbon Monoxide Poisoning; Carrier Proteins; Caspase Inhibitors; Caspases; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Nucleus; Culture Media; Cytochromes c; Enzyme Activation; Enzyme Inhibitors; Hippocampus; Humans; Hypoxia, Brain; Immunoblotting; Immunohistochemistry; Membrane Potentials; Mice; Microfilament Proteins; Mitochondria; Neurons; Phosphatidylserines; Propidium; Signal Transduction; Trypan Blue

A 26-year-old woman was admitted to our hospital for the treatment of hyperbaric oxygen therapy to acute carbon monoxide intoxication. The consciousness disturbance improved and she was discharged after 23 times of the hyperbaric oxygen therapy. However, she was readmitted because of dementia and urinary incontinence after 22 days. Diffusion-weighted images showed bright high signal intensities in the periventicular white matter and corpus callosum. The condition was considered to be an interval form of carbon monoxide intoxication. She was treated by 38 times of the hyperbaric oxygen therapy with cytochrome C and fully recovered. MRI images and cerebrospinal fluid abnormality (high protein content and IgG index) became normalized somewhat later than the improvement of the symptoms. By an investigation utilizing diffusion-weighted images, we thought that not only the demyelination which mentioned formerly, but the vasogenic edema was involving in the mechanism of these high signal intensities in the periventicular white matter of the interval form. And in the range which we searched, this is the first report which mentioned the abnormal findings of cerebrospinal fluid in an interval form of carbon monoxide intoxication. So we believe this case is very important for telling us suspected the mechanism and some indications about the treatment of an interval form.

Topics: Adult; Brain; Carbon Monoxide Poisoning; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cytochromes c; Dementia; Diffusion Magnetic Resonance Imaging; Female; Fetal Death; Humans; Hyperbaric Oxygenation; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Urinary Incontinence

Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Pharmacology; Radiation Injuries; Radiation Injuries, Experimental; Rats; Research

Topics: Animals; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Hypoxia; Lagomorpha; Rabbits; Research; Toxicology

Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes c; Electron Transport Complex IV; Energy Metabolism; Humans; Metabolism; Oxygen Consumption

Topics: Acid-Base Equilibrium; Alkalies; Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Guinea Pigs; Humans

Topics: Animals; Carbon Dioxide; Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Humans; Lagomorpha; Metabolism; Oxygen; Oxygen Consumption; Pharmaceutical Preparations; Rabbits

Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Poisoning

Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Heart; Humans; Poisoning

Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Cytochromes; Cytochromes c; Humans