Role of 3-ethylthiopropionate in ethionine metabolism and toxicity in rats.
The potential role of the pathway for ethionine catabolism involving the intermediate formation of 3-ethylthiopropionate in the etiology of ethionine hepatotoxicity was studied in rats. Rats were fed diets containing graded levels of 3-ethyl-thiopropionate, an intermediate of this pathway, for three weeks. A dietary level as low as 0.4% was toxic to rats, resulting in depressed growth and food intake, decreased blood hemoglobin levels and darkened and enlarged spleens. All animals fed 3-ethylthiopropionate expired a volatile sulfur compound that was identified as ethanethiol by gas chromatography using both a general flame ionization detector and a sulfur specific flame photometric detector. Rats fed diets containing either 0.8% ethionine or 3-ethylthiopropionate exhibited an 80% decrease in body weight gain over a three-week period compared to controls. Spleens were markedly darkened and enlarged and spleen iron content was 6-fold and 1.5-fold higher than controls in 3-ethylthiopropionate-fed and ethionine-fed rats, respectively. Liver concentrations of reduced and total glutathione were 30% higher than controls in ethionine-fed rats. There results document the marked toxicity of 3-ethylthiopropionate and ethionine and suggest that this pathway for ethionine catabolism may be involved in some of the numerous reported metabolic aberrations as a result of acute or chronic ingestion of ethionine.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005001:Ethionine / Q000633:toxicity*; D006454:Hemoglobins / Q000032:analysis; D008099:Liver / Q000187:drug effects; D008297:Male; D008715:Methionine / Q000633:toxicity; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects
D006454:Hemoglobins; D011422:Propionates; C021188:3-ethylthiopropionate; D008715:Methionine; D005001:Ethionine