2004 Fiscal Year Final Research Report Summary
Study on carbon monoxide toxicity independent of hypoxia
| Project/Area Number |
15590590
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
HARA Shuichi Tokyo Medical University, Medicine, Assistant Professor, 医学部, 講師 (70208651)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Carbon monoxide / Hydroxyl radical / Hypoxia / Glutamate / Calcium ion / Rat striatum / pO_2 / Blood flow |
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| Research Abstract |
1. Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min stimulated hydroxyl radical (・OH) generation in rat striatum.
(1) The CO-induced ・OH generation was suppressed by a voltage-dependent Na^+ channel blocker, tetrodotoxin (TTX).
(2) CO poisoning increased the extracellular glutamate (Glu) level, but Glu receptor antagonists (MK-801 and NBQX) had no effect on the ・OH generation.
(3) α-Methyl-p-tyrosine, clorgyline (Inhibitors of DA synthesis and oxidative metabolism, respectively) and dexamethazone 21-phosphate (a phospholipase A2 inhibitor) had no effect on the CO-induced ・OH generation.
(4) Nitric oxide (NO) synthase inhibitors and an NO precursor, L-arginine (L-Arg), and its enantiomer, D-Arg, had complex effects on the CO-induced ・OH generation. (This might be at least partly due to the nature of the striatum that may have a low ability to enhance NO production by utilising exogenous L-Arg.)
(5) The CO-induced ・OH generation was more slowly induced by the CO poisoning in the absence of extracellular Cat than in the presence of extracellular Ca^<2+>. The ・OH generation in the absence of extracellular Ca^<2+> was suppressed by dantrolene (an inhibitor of Ca^<2+> release from sarcoplasmic reticulum).
(6) Hypoxic hypoxia (HH; 5% O_2 for 40 min) stimulated ・OH generation in the striatum, though more wearly than the CO poisoning.
2. CO (3000 ppm for 40 min) and HH (5% O_2 for 40 min) induced similar changes in O_2 contents and oxyhemoglobin levels, but not pO_2, in arterial blood and extracellular amino acids (Glu, taurine and alanine), the blood flow and pO_2 in the striatum.
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