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.