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Role of 3-Ethylthiopropionate in Ethionine Metabolism and Toxicity in Rats¹

Department of Nutrition, Rutgers University, New Brunswick, NJ 08903

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-ethylthiopropionate, 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. These 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.

KEY WORDS: • ethionine • 3-ethylthiopropionate • hepatotoxicity • ethanethiol

¹ Supported by the New Jersey Agricultural Experiment Station, project 14422, and The Nutrition Foundation, Inc. This is a paper of the Journal Series, New Jersey Agricultural Experimental Station.

Manuscript received 20 July 1981.