RESUMO
(+)- and (-)-catechin showed opposite effects on glycogen metabolism in isolated rat hepatocytes. Addition of 0.5 mM catechin to hepatocytes from fasted rats resulted in the case of the (+)-isomer in a 90% stimulation and the case of the (-)-isomer in a 90% inhibition of net glycogen production. When 0.5 mM of the two isomers were added to hepatocytes from fed rats, (+)-catechin inhibited glycogenolysis by 33%, whereas the (-)-isomer stimulated the same process by 42%. At equal concentrations, the effects of (-)-catechin were stronger than those of the (+)-isomer. (-)-Epicatechin acted in a manner similar to (+)-catechin; however, the effect was less pronounced. (+)-Catechin antagonized the inhibitory action of suboptimal doses of glucagon on glycogen production whereby no change in basal or glucagon-elevated cyclic AMP level was observed. The activities of glycogen synthase a and glycogen phosphorylase a were changed by (+)- and (-)-catechin in a way corresponding to the changes in glycogen production and breakdown. (-)-Catechin, however, stimulated the activities of both glycogen synthase a and glycogen phosphorylase a in hepatocytes from fed rats. A possible interaction of the flavonoids or of their metabolites with glycogen phosphorylase is discussed.
Assuntos
Benzopiranos/farmacologia , Catequina/farmacologia , Glicogênio Hepático/metabolismo , Fígado/efeitos dos fármacos , Animais , Técnicas In Vitro , Cinética , Masculino , Ratos , Ratos Endogâmicos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Essential antioxidants were determined in plasma of middle-aged men representing 16 European study populations, which differed sixfold in age-specific mortality from ischemic heart disease (IHD). In 12 populations with "common" plasma cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors lacked significant correlations to IHD mortality, whereas absolute levels of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). Evaluating all populations, cholesterol and diastolic blood pressure were moderately associated, but their correlation was inferior to that of vitamin E. In stepwise regression and multiple regression analysis, mortality was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol), and to 87% by all the above parameters plus blood pressure. Thus, in the present study the cross-cultural differences of IDH mortality are primarily attributable to plasma status of vitamin E, which might have protective functions.
Assuntos
Doença das Coronárias/mortalidade , Vitamina E/sangue , Adulto , Pressão Sanguínea , Colesterol/sangue , Estudos de Coortes , Comparação Transcultural , Estudos Transversais , Europa (Continente)/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Fatores de RiscoRESUMO
For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the "Finland-Factor", the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid-standardized vitamin E >> carotene = vitamin C > vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following values: > 27.5-30.0 mumol vitamin E/L, 0.4-0.5 mumol carotene/L, 40-50 mumol vitamin C/L and 2.2-2.8 mumol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants.
Assuntos
Ácido Ascórbico/sangue , Carotenoides/sangue , Colesterol/sangue , Isquemia Miocárdica/sangue , Selênio/sangue , Vitamina E/sangue , Angina Pectoris/sangue , Pressão Sanguínea , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/prevenção & controle , Comparação Transcultural , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/prevenção & controle , Fatores de RiscoRESUMO
The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations. This inflammatory response produces reactive oxygen species and other cytotoxic substances, such as the cytokines. The generation of reactive oxygen species might deplete principal antioxidant micronutrients, that is, vitamins C and E and the carotenoids. Therefore, we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after randomization for previous vitamin E supplementation (300 mg dl-alpha-acetyl-tocopherol 3 times daily for 4 weeks) or placebo. Supplementation with alpha-tocopherol doubled the lipid-standardized plasma vitamin E concentration to 63.7 +/- 14.5 mumol/L when compared with that of the control subjects (31.2 +/- 9.0 mumol/L) before the operation. The plasma concentrations of vitamin C (36.0 +/- 19.0 mumol/L and 44.0 +/- 21.7 mumol/L, respectively) and of the carotenoids were not statistically different between the two groups at baseline. The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass, but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease. The vitamin E concentrations in the erythrocytes did not change either. In contrast, the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70%. Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks. In conclusion, the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations. In contrast, the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations.
Assuntos
Ácido Ascórbico/sangue , Ponte Cardiopulmonar , Vitamina E/sangue , Procedimentos Cirúrgicos Cardíacos , Carotenoides/sangue , Eritrócitos/química , Humanos , Pessoa de Meia-Idade , Pré-Medicação , Vitamina E/administração & dosagemRESUMO
A rapid method is described for the isolation of small volumes of plasma low density lipoprotein (LDL) free of plasma protein contaminants using the TL-100 Tabletop Ultracentrifuge (Beckman). The isolation of LDL was achieved by a 25 min discontinuous gradient density centrifugation between the density range of 1.006 and 1.21 g/ml, recovery of LDL by tube slicing followed by a 90 min flotation step (d = 1.12 g/ml). The purity of LDL and apolipoprotein B100 (apo B100) were monitored by agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), radial immunodiffusion and micropreparative fast protein liquid chromatography (FPLC). The ability of LDL oxidation was assessed by following absorbance at 234 nm after addition of copper ions. The functional integrity of the isolated LDL was checked by clearance kinetics after injection of [125I]-labelled LDL in estrogen-treated rats. The additional purification step led to LDL fractions free of protein contamination and left apo B100, alpha-tocopherol and beta-carotene intact. The LDL prepared in this way was free of albumin, as evident from analytic tests and from its enhanced oxidative modification by copper ions. Used for analytical purposes, this method allows LDL preparations from plasma volumes up to 570 microliters. This method is also convenient for metabolic studies in small animals, especially those relating to the determination of kinetic parameters of LDL in which LDL-apo B100 has to be specifically radiolabelled.
Assuntos
Lipoproteínas LDL/sangue , Lipoproteínas LDL/isolamento & purificação , Ultracentrifugação/métodos , Animais , Apolipoproteínas B/sangue , Carotenoides/sangue , Centrifugação com Gradiente de Concentração , Cromatografia Líquida/métodos , Cobre , Eletroforese em Gel de Ágar , Eletroforese em Gel de Poliacrilamida , Humanos , Imunodifusão , Lipoproteínas LDL/metabolismo , Oxirredução , Ratos , Vitamina E/sangue , beta CarotenoAssuntos
Antraquinonas/farmacologia , Antifúngicos/farmacologia , Mitocôndrias Hepáticas/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Animais , Antimicina A/farmacologia , Transporte de Elétrons , Ferricianetos , Hidroxibutiratos/metabolismo , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , NAD/metabolismo , Penicillium , Ratos , Succinatos/metabolismoAssuntos
Córtex Suprarrenal/metabolismo , Ácido Ascórbico/farmacologia , Hidrocortisona/metabolismo , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Córtex Suprarrenal/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Animais , Calcitriol/farmacologia , Células Cultivadas , Osteoblastos/efeitos dos fármacos , Ratos , SuínosRESUMO
In hepatocytes from starved rats, 10mM-glucose suppressed in incorporation of 2mM labelled alanine into glucose+glycogen by more than 40%, whereas no inhibition was observed with labelled lactate as substrate. Addition of glycerol instead of glucose did not show this inhibition. The inhibitory effect could also be demonstrated in label-free experiments.
Assuntos
Alanina/metabolismo , Carboidratos/biossíntese , Glucose/farmacologia , Lactatos/metabolismo , Fígado/metabolismo , Animais , Depressão Química , Glicerol/farmacologia , Técnicas In Vitro , Fígado/efeitos dos fármacos , Masculino , Ratos , Inanição/metabolismoRESUMO
D-Fructose 1,6-bisphosphate 1-phosphohydrolase (EC 3.1.3.11) was isolated from rat liver in two forms: "A," isolated in the presence, and "B," isolated in the absence of dithiothreitol. Both forms had an apparently identical molecular weight of approximately 37,000/subunit and the same Km for fructose 1,6-bisphosphate of 2 microM. However, the Ki of the AMP inhibition of form A was 140 microM and of form B, 370 microM. With form B the same inhibition as with form A was reached by incubating the enzyme with dithiothreitol. The two forms of the enzyme differed in their total, as well as in their number of fast reacting thiol groups. Form A was the more reduced form, exhibiting 22.4 thiol groups/molecule, 2.5 of them fast reacting with 5,5'-dithiobis-(2-nitrobenzoic acid). Only 0.5 fast reacting groups and a total of 19.2 were found with form B. The fast reacting thiol groups disappeared when assayed in the presence of AMP. It is suggested that a redox reaction alters a site that influences the inhibitory action of AMP, so as to regulate the activity of fructose 1,6-bisphosphatase.