Accumulation of 1-methyl-tetrahydro-Β-carboline-3-carboxylic acid in blood and organs of rat. A possible causative substance of eosinophilia-myalgia syndrome associated with ingestion ofl-tryptophan

Abstract

1-Methyl-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) may cause eosinophilia-myalgia syndrome (EMS) associated with ingestion of L-tryptophan. The distribution and excretion of MTCA were studied in rats which had received perorally a single 1.6 mg/kg dose of MTCA. MTCA concentrations in blood, kidney, liver, brain, heart, spleen, lung and gastrocnemius muscle were measured by HPLC combined with fluorometric detection. The concentration of MTCA in each organ reached a maximum at 1 h and then gradually declined. However, a significant level of MTCA still remained at 5 h, when 52% of ingested MTCA remained in the contents of the large intestine. Twenty-nine percent of the ingested MTCA was excreted in urine over the course of 24 h. A higher dose (10 mg/kg) of MTCA resulted in significant elevations in the concentrations and amounts of MTCA in the various organs. In addition, chronic treatment with a 10 mg/kg dose of MTCA for 6 weeks further increased the concentrations and amounts of MTCA in each organ. However, no histological changes were observed in any of the organs after chronic treatment. This is the first report which demonstrates accumulation of MTCA in the blood and various organs, including muscle, of rats.

Tetrahydro-β-carboline Alkaloids that Occur in Foods and Biological Systems Act as Radical Scavengers and Antioxidants in the ABTS Assay

“…Nevertheless, it has been reported that THbCs might be absorbed and accumulated in tissues. [31] Then, dietary sources rich in THbCs likely contribute to increase the amount of these compounds occurring in biological tissues and fluids, [2] where they might have a significant contribution by acting as radical scavengers. Foods containing high level of these compounds such as soy sauces and seasoning, wines, vinegars and fruit products (juices, jams, etc.…”

Tetrahydro-beta-carboline-3-carboxylic acid compounds in fish and meat: possible precursors of co-mutagenic beta-carbolines norharman and harman in cooked foods

“…Consequently, the diet along with a possible accumulation could explain their presence in tissues and biological¯uids. In this regard, experiments in rats have shown absorption and accumulation of TH C-3-COOHs in organs (Ogawa et al 1993). Although some research has already been accomplished on the biological signi® cance of TH Cs and Cs, further additional work is needed for its complete elucidation.…”

β-Carbolines That Accumulate in Human Tissues May Serve a Protective Role against Oxidative Stress

“…␤-Carbolines formed between hexulose, xylose, furan-2-carboxaldehyde, acetaldehyde, and glucose on the one hand and amino acids such as lysine, glycine, proline, arginine, histidine, and tryptophan on the other have been reported (5)(6)(7)(8)(9)(10). They are formed endogenously in plants and animals (for example, harmane, structure I in Fig.…”

“…On the other hand, there have been reports (14 -16) that some of these Maillard products are antioxidative in nature. ␤-Carbolines are found ubiquitously in a variety of foods: grain flour, soy sauce and soy protein, milk, beer, and wine, and perhaps as a consequence, in animal fluids and tissues such as blood, milk, urine, kidney, liver, and brain (10,17). Several reports have appeared in recent literature of the presence of ␤-carbolines in human tissues.…”