Protection by disulfiram and diethyldithiocarbamate against hypoxia-induced lethality in mice. 1993

T Masukawa, and K Nakanishi
Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.

The effects of disulfiram (DS) and its major metabolite, diethyldithiocarbamate (DEDC), on the survival time under normobaric and hypobaric hypoxia were examined in mice. At an ambient temperature of 24 degrees C, DS at 0.5-3.0 mmol/kg (i.p.) caused a marked dose-dependent prolongation of the survival time in mice subjected to both types of hypoxia. DEDC also prolonged the survival time, but the effect was less at its higher doses with decreased brain superoxide dismutase. The maximum effects of DS and DEDC were found at 3 hr and 1 hr after injection, respectively. Of the metabolites of DEDC, the copper complex with DEDC caused a significant effect, whereas neither diethylamine nor carbon disulfide did. Furthermore, DS, DEDC and copper complex caused marked hypothermia, and the time course changes of hypothermia by DS and DEDC closely paralleled those of the degree of anti-hypoxic effects, respectively. At an ambient temperature of 36 degrees C, in which the body temperature was maintained near the normal level, both DS and DEDC still exhibited a weak anti-hypoxic effect. These results suggest that DEDC itself, formed as a metabolite of DS, and partly the copper complex produced the anti-hypoxic effect, which could not be explained by concomitant hypothermia alone.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D009942 Organometallic Compounds A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed) Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D001831 Body Temperature The measure of the level of heat of a human or animal. Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003300 Copper A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55. Copper-63,Copper 63
D004050 Ditiocarb A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM. Diethyldithiocarbamate,Diethylcarbamodithioic Acid,Diethyldithiocarbamic Acid,Dithiocarb,Ditiocarb Sodium,Ditiocarb, Ammonium Salt,Ditiocarb, Bismuth Salt,Ditiocarb, Lead Salt,Ditiocarb, Potassium Salt,Ditiocarb, Sodium Salt,Ditiocarb, Sodium Salt, Trihydrate,Ditiocarb, Tin(4+) Salt,Ditiocarb, Zinc Salt,Imuthiol,Sodium Diethyldithiocarbamate,Thiocarb,Zinc Diethyldithiocarbamate,Ammonium Salt Ditiocarb,Bismuth Salt Ditiocarb,Diethyldithiocarbamate, Sodium,Diethyldithiocarbamate, Zinc,Lead Salt Ditiocarb,Potassium Salt Ditiocarb,Sodium Salt Ditiocarb,Sodium, Ditiocarb,Zinc Salt Ditiocarb
D004221 Disulfiram A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. Tetraethylthiuram Disulfide,Alcophobin,Antabus,Antabuse,Anticol,Bis(diethylthiocarbamoyl) Disulfide,Dicupral,Esperal,Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2,Teturam,Disulfide, Tetraethylthiuram
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies

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