Abstract
1-Methyl-tetrahydro-Β-carboline-3-carboxylic acid (MTCA) may cause eosinophilia-myalgia syndrome (EMS) associated with ingestion ofl-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.
This is a preview of subscription content, log in via an institution to check access.
References
Adachi J, Mizoi Y, Naito T, Ogawa Y, Uetani Y, Ninomiya I (1991a) Identification of tetrahydro-Β-carboline-3-carboxylic acid in foodstuffs, human urine and human milk. J Nutr 121: 646–652
Adachi J, Yamamoto K, Ogawa Y, Ueno Y, Mizoi Y, Tatsuno Y (1991b) Endogenous formation of 1-methyl-1,2,3,4-tetrahydro-Β-carboline-3-carboxylic acid in man as the possible causative substance of eosinophilia-myalgia syndrome associated with ingestion ofl-tryptophan. Arch Toxicol 65: 505–509
Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN, Loegering DA, Dunnette SL, Pirie PL, MacDonald KL, Osterholm MT (1990) An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med 323: 357–365
Brossi A, Focella A, Teitei S (1973) Alkaloids in mammalian tissues. 3. Condensation ofl-tryptophan andl-5-hydroxytryptophan with formaldehyde and acetaldehyde. J Med Chem 16: 418–420
Centers for Disease Control (1989) Eosinophilia-myalgia syndrome. New Mexico MMWR 38: 765–767
Crofford LJ, Rader JI, Dalakas MC, Hill RH, Page SW, Needham LL, Brady LS, Heyes MP, Wilder RL, Gold PW, Illa I, Smith C, Sternberg EM (1990)l-Tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat. J Clin Invest 86: 1757–1763
Ito J, Hosaki Y, Trigoe Y, Sakimoto K (1992) Identification of substances formed by decomposition of peak E substance in tryptophan. Food Chem Toxicol 30: 71–81
Mayeno AN, Lin F, Foote CS, Loegering DA, Ames MM, Hedberg CW, Gleich GJ (1990) Characterization of “peak E”, a novel amino acid associated with eosinophilia-myalgia syndrome. Science 250: 1707–1708
Nagahara A, Kumagai S (1991) Excretion and distribution of nitritetreated or untreated 1-methyl-1,2,3,4-tetrahydro-Β-carboline-3-carboxilic acid in rats. Food Chem Toxicol 29: 243–247
Sakimoto K (1990) The cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med 323: 992
Silver RM, Heyes MP, Maize JC, Quearry B, Vionnet-Fuasset M, Sternberg EM (1990) Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. N Eng J Med 322: 874–881
Smith MJ, Mazzola EP, Farrell TJ, Sphon JA, Page SW, Ashley D, Sirimanne SR, Hill RH, Needham LL (1991) 1,1′-Ethylidenebis (l-tryptophan), structure determination of contaminant “97”-implicated in the eosinophilia-myalgia syndrome (EMS). Tetrahedron Lett 32: 991–994
Yamada S, Akimoto H (1969) Reductive decyanization of α-amino nitriles with NaBH4. A new synthetic approach to isoquinoline- and indole-alkaloids. Tetrahedron Lett 3105–3108
Yamaguchi Y, Tsunoda J, Suda T, Miura Y, Nakano K, Kasahara T (1991) Effect of synthesized constituents in thel-tryptophan product on the differentiation of eosinophils and the induction of IL-6: A possible cause of eosinophilia-myalgia syndrome. Biochem Biophys Res Commun 178: 1008–1013
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogawa, Y., Adachi, J. & Tatsuno, Y. 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. Arch Toxicol 67, 290–293 (1993). https://doi.org/10.1007/BF01974349
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01974349