Document Detail


Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.
MedLine Citation:
PMID:  15337580     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.
Authors:
Jury Ju Ivnitsky; Timur V Schäfer; Vladimir N Malakhovsky; Vladimir L Rejniuk
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology     Volume:  202     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-08-31     Completed Date:  2004-10-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  165-72     Citation Subset:  IM    
Affiliation:
Military Toxicology and Medical Protection, Military Medical Academy, ul. Lebedeva 6, 194044 St. Petersburg, Russia. neugierig@mail.ru
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amobarbital / administration & dosage,  poisoning
Animals
Antidotes / administration & dosage,  therapeutic use*
Body Temperature / drug effects
Citric Acid Cycle / physiology*
Coma / chemically induced,  prevention & control
Female
Hypnotics and Sedatives / administration & dosage,  poisoning
Hypothermia / physiopathology,  prevention & control*
Injections, Intraperitoneal
Oxygen Consumption / drug effects*,  physiology
Poisoning / complications,  metabolism*,  prevention & control
Rats
Succinic Acid / metabolism,  therapeutic use
Thiobarbiturates / administration & dosage,  poisoning*
Thiopental / administration & dosage,  poisoning
Chemical
Reg. No./Substance:
0/Antidotes; 0/Hypnotics and Sedatives; 0/Thiobarbiturates; 110-15-6/Succinic Acid; 57-43-2/Amobarbital; 76-75-5/Thiopental

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of a novel organophosphorus pesticide (RPR-V) on extra hepatic detoxifying enzymes after rep...
Next Document:  Fumonisin B1-induced toxicity and oxidative damage in U-118MG glioblastoma cells.