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Abstract:

One of the three pathways for the metabolisation of dietary tryptophan is the formation of serotonin. Tryptophan hydroxylase catalyses the formation of 5-hydroxytryptophan, the first and regulatory step of this biosynthesis. The aim of the present work is to study alterations in this tryptophan metabolism in rats with experimental Porphyria Cutanea Tarda induced by hexachlorobenzene. With this purpose, the content of tryptophan and its metabolites related to the serotonin pathway are determined by HPLC techniques, in tissues (brain, liver and gut) and in fluids (blood, plasma and urine) of controls and hexachlorobenzene-porphyric rats. In these experimental-porphyric animals, we determine a significant increase in the excretion of 5-hydroxyindole acetic acid in urine and a decrease in the content of serotonin in small gut, respect to controls. Significant increases in contents of serotonin in 24-hr urine and tryptophan in liver are also found. No other significant variations for the different metabolites are detected in any of the tissues and fluids studied. Brain and liver activities of the rate-limiting enzyme tryptophan hydroxylase can only be measured in porphyric rats. Our results agree with an increased turnover of gastrointestinal serotonin derived from dietary tryptophan and its excretion as urinary 5-hydroxyindole acetic acid, which is formed in liver. An increased serotonin pathway in porphyric livers is confirmed by the measured increase in the activity of hepatic tryptophan hydroxylase. The absence of neurological symptoms in patients with Porphyria Cutanea Tarda could be related to the absence of a statistically significant variation in serotonin content shown in brain. © 2003 Elsevier Science Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria
Autor:Llambías, E.B.C.; Aldonatti, C.; San Martín De Viale, L.C.
Filiación:Depto. de Quím. Biol., Fac. de Ciencias Exactas y Naturales, Pabellón II, 1428 Buenos Aires, Argentina
O'Higgins 4332, 1429 Buenos Aires, Argentina
Palabras clave:Experimental hepatic porphyria; Hexachlorobenzene; Metabolites of tryptophan pathway via serotonin; Porphyria Cutanea Tarda; Tryptophan; Tryptophan hydroxylase; 5 hydroxyindoleacetic acid; 5 hydroxytryptophan; hexachlorobenzene; serotonin; tryptophan; tryptophan hydroxylase; amino acid blood level; amino acid urine level; animal experiment; animal model; animal tissue; article; controlled study; enzyme activity; female; high performance liquid chromatography; nonhuman; porphyria cutanea tarda; priority journal; protein metabolism; rat; regulatory mechanism; tissue level; tryptophan brain level; tryptophan metabolism; urinary excretion
Año:2003
Volumen:66
Número:1
Página de inicio:35
Página de fin:42
DOI: http://dx.doi.org/10.1016/S0006-2952(03)00241-7
Título revista:Biochemical Pharmacology
Título revista abreviado:Biochem. Pharmacol.
ISSN:00062952
CODEN:BCPCA
CAS:5 hydroxyindoleacetic acid, 1321-73-9, 54-16-0; 5 hydroxytryptophan, 4350-09-8, 56-69-9; hexachlorobenzene, 118-74-1, 55600-34-5; serotonin, 50-67-9; tryptophan, 6912-86-3, 73-22-3; tryptophan hydroxylase, 9037-21-2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v66_n1_p35_Llambias

Referencias:

  • De Matteis, F., Prior, B.E., Rimington, C., Nervous and biochemical disturbances following hexachlorobenzene intoxication (1961) Nature, 191, pp. 363-366
  • San Martín de Viale, L.C., Viale, A., Nacht, S., Grinstein, M., Experimental porphyria induced in rats by hexachlorobenzene. A study of the porphyrins excreted by urine (1970) Clin. Chim. Acta, 28, pp. 13-23
  • Wainstok de Calmanovici, R., Rios de Molina, M.C., Taira de Yamasato, M.C., Tomio, J.M., San Martín de Viale, L.C., Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment (1984) Biochem. J., 218, pp. 753-763
  • Smith, A.G., De Matteis, F., Drugs and the hepatic porphyrias (1980) Clin. Haematol., 9, pp. 399-425
  • De Salamanca, R.E., Batlle A.M. del, C., Chinarro, S., Stella, A.M., Wider, E.A., Estudio comparativo de la porfiria experimental inducida por hexaclorobenceno y la porfiria cutanea tarda humana (1985) Ann. Med. Int., 2, pp. 319-329
  • Elder, G.H., Porphyria Cutanea Tarda (1998) Semin. Liver Dis., 18, pp. 67-75
  • Bleavins, M.R., Bursian, S.J., Brewster, J.S., Aulerich, R.J., Effects of dietary hexachlorobenzene exposure on regional brain biogenic amine concentrations in mink and European ferrets (1984) J. Toxicol. Environ. Health, 14, pp. 363-377
  • Jackson, A.H., Jenkins, R.T., Grinstein, M., Ferramola de Sancovich, A.M., Sancovich, H.A., The isolation and identification of indigoid pigments from urine (1988) Clin. Chim. Acta, 172, pp. 245-252
  • Diesbach, H., Wiederkehr, F.X., Indirubine et indileucine (1945) Helv. Chim. Acta, 28, pp. 690-700
  • Rimington, C., Holiday, E.R., Jope, E.M., Indigoid pigments derived from pathological urine (1948) Biochem. J., 40, pp. 669-677
  • Bearcroft, C.P., Farthing, M.J.G., Perrett, D., Determination of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and tryptophan in plasma and urine by HPLC with fluorimetric detection (1995) Biomed. Chromatogr., 9, pp. 23-27
  • Badawy, A.A.B., Evans, M., The regulation of rat liver tryptophan pyrrolase by its cofactor haem. Experiments with haematin and 5-aminolaevulinate and comparison with the substrate and hormonal mechanisms (1975) Biochem. J., 150, pp. 511-520
  • Goke, B., Richter, G., Grebe, A., Keim, V., Arnold, R., Tryptophan rich diet as a new approach to study the serotoninergic enteropancreatic axis (1987) Gut, 51, pp. 203-205
  • Alexander, B., Aslam, M., Nobin, A., Benjamin, I.S., Differentiation between the effects of unprocessed portal blood and reduced liver function on brain indole amine metabolism in the portacaval shunted rat (1998) Metab. Brain Dis., 13, pp. 137-146
  • Bortolozzi, A.A., Sartorio, C., Duffard, R.O., Evangelista de Duffard, A.M., Peripheral serotoninergic system alterations in rats exposed during different periods of their life to neurotoxic 2,4-dichlorophenoxyacetic acid (1998) Biogenic Amines, 14, pp. 667-689
  • Billi de Cattabi, S.C., Aldonatti, C., San Martín de Viale, L.C., Heme metabolism after discontinued hexachlorobenzene administration in rats: Possible irreversible changes and biomarkers for hexachlorobenzene persistence (2000) Comp. Biochem. Physiol. Part C, 127, pp. 165-175
  • Xiao, R., Beck, O., Hjemdahl, P., On the accurate measurement of serotonin in whole blood (1998) Scand. J. Clin. Lab. Invest., 58, pp. 505-510
  • Wolf, W.A., Kuhn, D.M., Simultaneous determination of 5-hydroxytryptamine, its amino acid precursors and acid metabolite in discrete brain regions by high-performance liquid chromatography with fluorescence detection (1983) J. Chromatogr., 275, pp. 1-9
  • Moran, G.R., Fitzpatrick, P.F., A continuous fluorescence assay for tryptophan hydroxylase (1999) Anal. Biochem., 266, pp. 148-152
  • Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with the Folin phenol reagent (1951) J. Biol. Chem., 193, pp. 265-275
  • Bearcroft, C.P., Perrett, D., Farthing, M.J.G., Postprandial plasma 5-hydroxytryptamine in diarrhea predominant irritable bowel syndrome: A pilot study (1998) Gut, 42, pp. 42-46
  • Alfieri, A.B., Cubeddu, L.X., Effect of inhibition of serotonin synthesis on 5-hydroxyindole acetic acid excretion, in healthy subjects (1994) J. Clin. Pharmacol., 34, pp. 153-157
  • Tyce, G.M., Biochemistry of serotonin (1995) Serotonin and the Cardiovascular System, pp. 1-13. , Vanhoutte PM, editor. New York: Raven Press
  • Weber, L.W.D., Stahl, B.V., Rozman, K., Are serotoninergic mechanisms involved in the acute toxicity of chlorinated dibenzo-p-dioxins (CDDs) (1992) Chemosphere, 25, pp. 161-164
  • Billi de Catabbi, S., Sterin-Speziale, N., Fernández, M.C., Minutolo, C., Aldonatti, C., San Martín de Viale, L.C., Time course of hexachlorobenzene-induced alterations of lipid metabolism and their relation to porphyria (1997) Int. J. Biochem. Cell Biol., 29, pp. 335-344
  • Mazzetti, M., Taira, C., Lelli, S., Dascal, E., Karabatas, L., San Martín de Viale, L.C., Alterations of glucose metabolism in hexachlorobenzene porphyria model Proceedings of Millenium Meeting on Porphyrins and Porphyrias 2000, , Institut Pasteur, Paris, France, September 10-13, 2000. Université Paris VII: Centre Français des Porphyries, Hôpital Louis Mourier (AP-HP), Inserm U 409, UFR Xavier Bichart; 2000. p. 30 [Abstract 066]
  • Cochon, A.C., González, N., San Martín de Viale, L.C., Effects of the porphyrinogenic compounds hexachlorobenzene and 3,5-diethoxycarbonyl-1,4-dihydrocollidine on polyamine metabolism (2002) Toxicology, 176, pp. 209-219

Citas:

---------- APA ----------
Llambías, E.B.C., Aldonatti, C. & San Martín De Viale, L.C. (2003) . Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria. Biochemical Pharmacology, 66(1), 35-42.
http://dx.doi.org/10.1016/S0006-2952(03)00241-7
---------- CHICAGO ----------
Llambías, E.B.C., Aldonatti, C., San Martín De Viale, L.C. "Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria" . Biochemical Pharmacology 66, no. 1 (2003) : 35-42.
http://dx.doi.org/10.1016/S0006-2952(03)00241-7
---------- MLA ----------
Llambías, E.B.C., Aldonatti, C., San Martín De Viale, L.C. "Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria" . Biochemical Pharmacology, vol. 66, no. 1, 2003, pp. 35-42.
http://dx.doi.org/10.1016/S0006-2952(03)00241-7
---------- VANCOUVER ----------
Llambías, E.B.C., Aldonatti, C., San Martín De Viale, L.C. Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria. Biochem. Pharmacol. 2003;66(1):35-42.
http://dx.doi.org/10.1016/S0006-2952(03)00241-7