The effect of naftidrofuryl on cyanide-induced hypoxic damage to glucose and energy metabolism in brain cortex of rats.
Increasing life expectancy increases diseases of old age. Dementia is a highly age-related brain disease in which the metabolic rates of oxygen and glucose are predominantly disturbed. However, related changes in metabolism at the molecular level are rather little known. Knowledge on pharmacotherapeutic modification of the metabolic variations in the brains of demented people is also scanty. Since the vascular type of primary dementia is found to be associated with metabolic variations which resemble that of a cerebral hypoxia, hypoxic brain damage was produced by means of a sublethal dosage of cyanide in two-year-old rats. The cyanide-induced damage in brain metabolism was characterized by an increase of the tricarboxylic acid cycle intermediates succinate, fumarate and malate. This indicates disturbances of NAD+- and FAD+-dependent redox reactions also including pyruvate oxidation. Lactate production was found to be increased, and creatine phosphate formation reduced. Application of 3 mg/kg naftidrofuryl after cyanide damage produced a normalizing effect on the cyanide-induced changes in glucose and energy metabolism of brain cortex of rats. The tentative conclusion may thus be drawn that naftidrofuryl may have a beneficial effect on cyanide-induced hypoxic brain damage. Whether this drug might be useful in other brain hypoxic conditions remains to be investigated.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003486:Cyanides; D004734:Energy Metabolism / Q000187:drug effects*; D005663:Furans / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000378:metabolism*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009257:Nafronyl / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003486:Cyanides; D005663:Furans; D006454:Hemoglobins; D007773:Lactates; D002245:Carbon Dioxide; D019344:Lactic Acid; D009257:Nafronyl; D005947:Glucose