Protection against acetaldehyde toxicity in the rat by L-cysteine, thiamin and L-2-methylthiazolidine-4-carboxylic acid.

Abstract

Acetaldehyde is 10–30 times more toxic than ethanol and has been implicated in alcoholic cardiomyopathy. Its oral LD50 and LD90 Litchfield-Wilcoxon values were found to be 15.0 (14.4–15.6) mM/kg and 18.0 (15.5–20.5) mM/kg, respectively. Protection against acetaldehyde lethality was obtained by oral intubation of test compounds 30–45 minutes prior to oral intubation of 18 mM/kg of acetaldehyde. At 2.0 mM/kg, survival after 24–72 hours withl-cysteine free base(FB)was80%;withl-2-methylthiazolidine-4-carboxylic acid (l-MTCA), 75%; with thiamin·HCl, 90%; and only 10% with saline control. At 0.3 mM/kg, thiamin·HCl gave virtually no protection (13% survival). The combination ofl-cysteine FB plus thiamin·HCl, each at 2.0 mM/kg, gave 100% survival. The oral LD50 dose (Litchfield-Wilcoxon) in mM/kg forl-cysteine FB was 15.6(14.8–16.4); forl-MTCA, 17.9 (17.0–18.8), and for thiamin·HCl, 11.0 (10.4–11.6). The ratio of toxic dose-protective dose of the first two compounds warrants further study of them in combination with thiamin as possible protective agents against the chronic toxicity of acetaldehyde associated with heavy ethanol intake and heavy smoking.