Acetaldehyde-induced formation of 1-methyl-1, 2,3,4-tetrahydro-β-carboline-3-carboxylic acid in rats

Abstract

1-Methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) is one of the metabolites of peak E substance, which, based on epidemiological studies, has been thought to be a possible causative agent of the tryptophan-induced eosinophiua-myalgia syndrome. Acute ethanol and l-tryptophan administration in rats pretreated with cyanamide resulted in the formation of MTCA. Concentrations of MTCA were estimated at 27 ng/g in blood and 33 ng/g in kidneys. Chronic treatment with a liquid diet containing ethanol as 36% of the total calories for 6 weeks increased these levels. MTCA was barely observed in rats that had received acute or chronic ethanol in the absence of cyanamide, or in the cyanamide-tryptophan controls. Cyanamide facilitation of ethanol-dependent MTCA biosynthesis may be due to a potentiation of the blood level of acetaldehyde derived from ethanol. The blood acetaldehyde level in rats that had been acutely treated with cyanamide, ethanol and l-tryptophan was 348 μM, and averaged 503 μM in rats that received the same treatment after chronic consumption of ethanol. In contrast to the above findings, l-tryptophan intake promoted the formation of 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (TCCA) in rats. This is the first report of MTCA in mammalian tissue during tryptophan and ethanol metabolism.