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Abstract:

Acute hepatic porphyrias are human metabolic diseases characterized by the accumulation of heme precursors, such as 5-aminolevulinic acid (ALA). The administration of glucose can prevent the symptomatology of these diseases. The aim of this work was to study the relationship between glucose metabolism disturbances and the development of experimental acute hepatic porphyria, as well as the role of reactive oxygen species (ROS) through assays on hepatic key gluconeogenic and glycogenolytic enzymes; phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP), respectively. Female Wistar rats were treated with three different doses of the porphyrinogenic drug 2-allyl-2-isopropylacetamide (AIA) and with a single dose of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Thus, rats were divided into the following groups: group L (100 mg AIA + 50 mg DDC/kg body wt.); group M (250 mg AIA + 50 mg DDC/kg body wt.) and group H (500 mg AIA + 50 mg DDC/kg body wt.). The control group (group C) only received vehicles (saline solution and corn oil). Acute hepatic porphyria markers ALA-synthase (ALA-S) and ferrochelatase, heme precursors ALA and porphobilinogen (PBG), and oxidative stress markers superoxide dismutase (SOD) and catalase (CAT) were also measured in hepatic tissue. On the other hand, hepatic cytosolic protein carbonyl content, lipid peroxidation and urinary chemiluminescence were determined as in vivo oxidative damage markers. All these parameters were studied in relation to the different doses of AIA/DDC. Results showed that enzymes were affected in a drug-dose-dependent way. PEPCK activity decreased about 30% in group H with respect to groups C and L, whereas GP activity decreased 53 and 38% in group H when compared to groups C and L, respectively. On the other hand, cytosolic protein carbonyl content increased three-fold in group H with respect to group C. A marked increase in urinary chemiluminescence and a definite increase in lipid peroxidation were also detected. The activity of liver antioxidant enzyme SOD showed an induction of about 235% in group H when compared to group C, whereas CAT activity diminished due to heme depletion caused by both drugs. Based on these results, we can speculate that the alterations observed in glucose metabolism enzymes could be partly related to the damage caused by ROS on their enzymatic protein structures, suggesting that they could be also linked to the beneficial role of glucose administration in acute hepatic porphyria cases. © 2005 Elsevier Ireland Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species
Autor:Lelli, S.M.; De Viale, L.C.S.M.; Mazzetti, M.B.
Filiación:Laboratorio de Disturbios Metabólicos Por Xenobióticos, Salud Humana Y Medio Ambiente, Departamento de Química Biológica, Pab. II, Cd. Autónoma de Buenos Aires, Argentina
Palabras clave:Acute porphyria model; Glucose metabolism; Rat liver; Reactive oxygen species; 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester; 5 aminolevulinate synthase; allylisopropylacetamide; aminolevulinic acid; carbonyl derivative; catalase; corn oil; ferrochelatase; glycogen phosphorylase; liver protein; phosphoenolpyruvate carboxykinase (GTP); porphobilinogen; reactive oxygen metabolite; sodium chloride; superoxide dismutase; acute intermittent porphyria; animal experiment; animal model; animal tissue; article; chemoluminescence; controlled study; enzyme activity; enzyme induction; female; glucose metabolism; lipid peroxidation; liver level; nonhuman; oxidative stress; priority journal; rat; Allylisopropylacetamide; Animals; Chemiluminescent Measurements; Dicarbethoxydihydrocollidine; Disease Models, Animal; Female; Glucose; Heme; Lipid Peroxidation; Liver; Porphyria, Acute Intermittent; Rats; Rats, Wistar; Reactive Oxygen Species; Urine; Animalia; Rattus norvegicus; Zea mays
Año:2005
Volumen:216
Número:1
Página de inicio:49
Página de fin:58
DOI: http://dx.doi.org/10.1016/j.tox.2005.07.016
Título revista:Toxicology
Título revista abreviado:Toxicology
ISSN:0300483X
CODEN:TXCYA
CAS:1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester, 12772-36-0, 632-93-9; 5 aminolevulinate synthase, 9037-14-3; allylisopropylacetamide, 299-78-5; aminolevulinic acid, 106-60-5; catalase, 9001-05-2; corn oil, 8001-30-7; ferrochelatase, 9012-93-5; glycogen phosphorylase, 9032-10-4; phosphoenolpyruvate carboxykinase (GTP), 9013-08-5; porphobilinogen, 487-90-1; sodium chloride, 7647-14-5; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; Allylisopropylacetamide, 299-78-5; Dicarbethoxydihydrocollidine, 632-93-9; Glucose, 50-99-7; Heme, 14875-96-8; Reactive Oxygen Species
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0300483X_v216_n1_p49_Lelli

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Citas:

---------- APA ----------
Lelli, S.M., De Viale, L.C.S.M. & Mazzetti, M.B. (2005) . Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species. Toxicology, 216(1), 49-58.
http://dx.doi.org/10.1016/j.tox.2005.07.016
---------- CHICAGO ----------
Lelli, S.M., De Viale, L.C.S.M., Mazzetti, M.B. "Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species" . Toxicology 216, no. 1 (2005) : 49-58.
http://dx.doi.org/10.1016/j.tox.2005.07.016
---------- MLA ----------
Lelli, S.M., De Viale, L.C.S.M., Mazzetti, M.B. "Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species" . Toxicology, vol. 216, no. 1, 2005, pp. 49-58.
http://dx.doi.org/10.1016/j.tox.2005.07.016
---------- VANCOUVER ----------
Lelli, S.M., De Viale, L.C.S.M., Mazzetti, M.B. Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species. Toxicology. 2005;216(1):49-58.
http://dx.doi.org/10.1016/j.tox.2005.07.016