Synergism between mercaptans and ammonia or fatty acids in the production of coma: a possible role for mercaptans in the pathogenesis of hepatic coma.

Abstract

Abstract The coma-producing properties of methanethiol, ethanethiol, and dimethyl sulfide were studied in rats. Coma occurred in 50 per cent of rats when the air breathed contained 0.16 per cent methanethiol, 3.3 per cent ethanethiol, or 9.6 per cent dimethyl sulfide by volume. The blood concentrations at which coma occurred were: methanethiol 0.5, ethanethiol 200, and dimethyl sulfide 7,000 nanomoles per milliliter. These compounds had a pronounced synergistic effect on the coma-producing potential of ammonium salts and fatty acids. The doses of NH 4 + or octanoate at which rats went into coma were reduced markedly when subcoma doses of mercaptans were given simultaneously. The addition of small subcoma doses of methanethiol to subcoma doses of NH 4 + caused coma in all animals and a substantial rise in blood ammonia. Conversely, the addition of small subcoma doses of NH 4 + or of fatty acid to a small subcoma dose of methanethiol caused coma in all animals and a marked rise in blood methanethiol concentration. At blood (or plasma) levels of methanethiol, ammonia, and free fatty acids such as were found in hepatic coma following acute massive necrosis of the liver, normal rats became comatose. The synergistic action of these 3 toxic substances seemed sufficient to account for the coma of experimental hepatic necrosis. We infer that methanethiol probably plays a role as an augmenter or intensifier of the toxic effects of ammonia and fatty acids in human hepatic failure.