Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate.
1. The lethal, hypoglycaemic and hypothermic effects of hypoglycin in fasted rats are prevented if the rats had been fed on a diet containing clofibrate (0.5% w/w). 2. Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria [Tanaka (1972) J. Biol. Chem. 247, 7465-7478]. 3. Rats maintained on a diet containing clofibrate appeared normal after injection of hypoglycin, but had a marked dicarboxylic aciduria which was less than that induced in rats on a normal diet. 4. After administration of hypoglycin, butyryl-CoA and decanoyl-CoA, but not palmitoyl-CoA, dehydrogenase activities were strongly inhibited (80-95%) in the livers of animals on a standard diet. 5. Clofibrate feeding decreased the inhibition of these dehydrogenases to about 40-60%. 6. It was concluded that although clofibrate protects against the toxic effects of hypoglycin, some enzyme inhibitions as indicated by dicarboxylic aciduria are only partly prevented.
Department of Pharmacological Sciences, Medical School, University of Newcastle upon Tyne, U.K.
R K
RK
Veitch
H S
HS
Sherratt
K
K
Bartlett
D000818:Animals; D002849:Chromatography, Gas; D002994:Clofibrate / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000506:poisoning*; D003998:Dicarboxylic Acids / Q000652:urine*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D007005:Hypoglycins / Q000506:poisoning*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010939:Plant Poisoning / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D003521:Cyclopropanes; D003998:Dicarboxylic Acids; D007005:Hypoglycins; C041757:hypoglycin; D044943:Fatty Acid Desaturases; D002994:Clofibrate