Alterations of the redox state, pentose pathway and glutathione metabolism in an acute porphyria model. their impact on heme pathway

A classical acute porphyria model in rats consists of combined treatment with 2-allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). The present work describes the effects of this treatment on the pentose phosphate (PP) pathway, glutahione metabolism and redox state...

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Autor principal: Faut, M.
Otros Autores: Paiz, A., de Viale, L.C.S.M, Mazzetti, M.B
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2013
Acceso en línea:Registro en Scopus
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Registro en la Biblioteca Digital
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024 7 |2 cas  |a 5 aminolevulinate synthase, 9037-14-3; glucose, 50-99-7, 84778-64-3; glucose 6 phosphate dehydrogenase, 37259-83-9, 9001-40-5; glutathione, 70-18-8; glutathione disulfide, 27025-41-8; glutathione peroxidase, 9013-66-5; glutathione reductase, 9001-48-3; glutathione transferase, 50812-37-8; heme, 14875-96-8; phosphogluconate dehydrogenase, 9001-82-5; 3,5-diethoxycarbonyl-1,4-dihydrocollidine; Allylisopropylacetamide, 299-78-5; Glucose, 50-99-7; Glucosephosphate Dehydrogenase, 1.1.1.49; Glutathione, 70-18-8; Glutathione Disulfide, 27025-41-8; Glutathione Peroxidase, 1.11.1.9; Glutathione Reductase, 1.8.1.7; Glutathione Transferase, 2.5.1.18; Heme, 14875-96-8; NADP, 53-59-8; Pyridines; Reactive Oxygen Species 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a EBMMB 
100 1 |a Faut, M. 
245 1 0 |a Alterations of the redox state, pentose pathway and glutathione metabolism in an acute porphyria model. their impact on heme pathway 
260 |c 2013 
270 1 0 |m Mazzetti, M. B.; Laboratorio de Disturbios Metabólicos por Xenobióticos, Salud Humana y Medio Ambiente, Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, 4to Piso, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina; email: mazzetti@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a A classical acute porphyria model in rats consists of combined treatment with 2-allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). The present work describes the effects of this treatment on the pentose phosphate (PP) pathway, glutahione metabolism and redox state and how they contribute to alter the glucose pool of hepatocytes and modulate porphyria, in Wistar rat livers. Our approach is based on the fact that glucose is a repressor of 5-aminolevulinic synthase (ALA-S), the rate-limiting enzyme of the heme pathway, and treatment with AIA/DCC causes oxidative stress. Different doses of the xenobiotcs were used. The results show that AIA (500 mg/kg body weight [BW])/ DDC (50 mg/kg [BW]) treatment increased glutathione peroxidase (GPx) activity by 46%, decreased both glutathione reductase (GR) and glutathione S-transferase (GST) activity by 69% and 52%, respectively, and reduced by 51% reduced glutathione (GSH) and increased by 100% glutathione disulfide (GSSG) concentrations, therefore lowering by four-fold the GSH/GSSG ratio. The activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of PP-pathway, was increased by 129% as well as that of 6-phosphogluconate dehydrogenase. NADPH and the NADPH/NADP+ ratio were increased by 14% and 28%, respectively. These effects could be attributed to the generation of reactive oxygen species (ROS) elicited by the porphyrinogenic treatment, shown by enhanced DNA damage and ROS production. G6PD stimulation would decrease hepatic glucose concentrations and consequently exacerbate the porphyria. A decrease in glucose could stimulate ALA-S and this would add to the effect of drug-induced heme depletion. Since the key role of GST is to inactivate toxic compounds, the drastic fall in its activity together with the accumulation of ALA would account for the symptoms of this hepatic disease model. The present findings show the high metabolic interplay between pathways and constitute a relevant contribution to achieve a better treatment of acute human porphyria. © 2013 by the Society for Experimental Biology and Medicine.  |l eng 
593 |a Laboratorio de Disturbios Metabólicos por Xenobióticos, Salud Humana y Medio Ambiente, Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, 4to Piso, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina 
690 1 0 |a GLUCOSE-6-PHOSPHATE DEHYDROGENASE 
690 1 0 |a GLUTATHIONE METABOLISM 
690 1 0 |a PENTOSE PHOSPHATE PATHWAY 
690 1 0 |a PORPHYRIA 
690 1 0 |a RAT LIVER 
690 1 0 |a REACTIVE OXYGEN SPECIES 
690 1 0 |a 5 AMINOLEVULINATE SYNTHASE 
690 1 0 |a GLUCOSE 
690 1 0 |a GLUCOSE 6 PHOSPHATE DEHYDROGENASE 
690 1 0 |a GLUTATHIONE 
690 1 0 |a GLUTATHIONE DISULFIDE 
690 1 0 |a GLUTATHIONE PEROXIDASE 
690 1 0 |a GLUTATHIONE REDUCTASE 
690 1 0 |a GLUTATHIONE TRANSFERASE 
690 1 0 |a HEME 
690 1 0 |a PHOSPHOGLUCONATE DEHYDROGENASE 
690 1 0 |a PYRIDINE NUCLEOTIDE 
690 1 0 |a REACTIVE OXYGEN METABOLITE 
690 1 0 |a ACUTE INTERMITTENT PORPHYRIA 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ARTICLE 
690 1 0 |a BLOOD SAMPLING 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DNA DAMAGE 
690 1 0 |a ENZYME LINKED IMMUNOSORBENT ASSAY 
690 1 0 |a FEMALE 
690 1 0 |a GLUTATHIONE METABOLISM 
690 1 0 |a NONHUMAN 
690 1 0 |a OXIDATION REDUCTION STATE 
690 1 0 |a OXIDATIVE STRESS 
690 1 0 |a PENTOSE PHOSPHATE CYCLE 
690 1 0 |a PROTEIN DETERMINATION 
690 1 0 |a RAT 
690 1 0 |a SPECTROPHOTOMETRY 
690 1 0 |a URINALYSIS 
690 1 0 |a ALLYLISOPROPYLACETAMIDE 
690 1 0 |a ANIMALS 
690 1 0 |a DISEASE MODELS, ANIMAL 
690 1 0 |a GLUCOSE 
690 1 0 |a GLUCOSEPHOSPHATE DEHYDROGENASE 
690 1 0 |a GLUTATHIONE 
690 1 0 |a GLUTATHIONE DISULFIDE 
690 1 0 |a GLUTATHIONE PEROXIDASE 
690 1 0 |a GLUTATHIONE REDUCTASE 
690 1 0 |a GLUTATHIONE TRANSFERASE 
690 1 0 |a HEME 
690 1 0 |a LIVER 
690 1 0 |a NADP 
690 1 0 |a OXIDATION-REDUCTION 
690 1 0 |a OXIDATIVE STRESS 
690 1 0 |a PENTOSE PHOSPHATE PATHWAY 
690 1 0 |a PORPHYRIA, ACUTE INTERMITTENT 
690 1 0 |a PYRIDINES 
690 1 0 |a RATS 
690 1 0 |a REACTIVE OXYGEN SPECIES 
700 1 |a Paiz, A. 
700 1 |a de Viale, L.C.S.M. 
700 1 |a Mazzetti, M.B. 
773 0 |d 2013  |g v. 238  |h pp. 133-143  |k n. 2  |p Exp. Biol. Med.  |x 15353702  |t Experimental Biology and Medicine 
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