Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking.

Acetaldehyde is a toxic substance common to heavy drinking of alcohol and heavy smoking of cigarettes. It has been implicated thereby in diseases of the cardiovascular, respiratory, and central nervous systems. Protection against acetaldehyde toxicity (i.e. anesthesia and lethality) was studied in rats by oral intubation of test compounds 30-45 minutes prior to oral intubation of a standardized oral LD 90 dose (18 millimoles/kilogram) of acetaldehyde. Animals were monitored for anesthesia (loss of righting reflexes) and lethality for 72 hours. A total of 18 compounds was tested. L-ascorbic acid at 2 millimoles/kilogram (mM/kg) showed moderate protection against anesthesia and marked protection against lethality. Greatest protection against anesthesia and lethality was obtained at 2 m M/kg with each of the following: L-cysteine, N-acetyl-L-cysteine, thiamin-HCl, sodium metabisulfite, and L-cysteic acid. A combination of L-ascorbic acid with L-cysteine, and thiamin-HCl at reduced dose levels (2.0, 1.0 and 0.3 mM/kg, respectively) gave virtually complete protection. A detailed literature review is presented of the rationale and significance of these findings. Our findings could point the way to a possible build-up of natural protection against the chronic body insult of acetaldehyde arising from heavy drinking of alcohol and heavy smoking of cigarettes.