RESUMO
Changes in different microsomal membrane functions were measured in the liver of rats 3, 6, or 9 weeks following an oral infection with 20 metacercariae of Fasciola hepatica. The parasitic pathology noted at autopsy was accompanied by increased levels in both plasma aspartate aminotransferase (EC 2.6.1.1) and microsomal gamma-glutamyltransferase (EC 2.3.2.2). Heme oxygenase activity of microsomes was significantly decreased by Weeks 3 and 6 postinfection and this decrease correlates with those of total microsomal cytochrome P450 and certain P450-dependent monooxygenase activities, namely, benzphetamine demethylation, ethoxycoumarin deethylation, and benzopyrene hydroxylation. Microsomal epoxide hydrolase (EC 3.3.2.3) was only altered 6 weeks after the infection. During the early stages of the parasitism, there were decreases in both microsomal calcium uptake and calcium ATPphosphohydrolase activity (EC 2.6.1.1), whereas membrane fluidity, estimated by the order parameter S, was lower in the infected rats than that in the controls. These alterations could be related to the already described increase in liver cytosolic calcium or lipid peroxidation which occurs in experimental fascioliasis.
Assuntos
Fasciola hepatica/fisiologia , Fasciolíase/enzimologia , Fígado/parasitologia , Microssomos Hepáticos/enzimologia , Animais , Aspartato Aminotransferases/sangue , Benzopireno Hidroxilase/metabolismo , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Epóxido Hidrolases/metabolismo , Fasciolíase/metabolismo , Fasciolíase/patologia , Heme Oxigenase (Desciclizante)/metabolismo , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/patologia , Masculino , Oxirredutases N-Desmetilantes/metabolismo , Ratos , Ratos Sprague-Dawley , gama-Glutamiltransferase/metabolismoRESUMO
Sprague-Dawley rats were fed for 4 months on a control diet or a polyunsaturated-fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed. Inflammation implied an increase in lipid peroxidation, Fe storage and caeruloplasmin concentration, together with symptoms of anaemia. PUFA deficiency in inflamed rats gave rise to a lower inflammatory response (granuloma weight and prostaglandin E2 concentration) and ethane exhalation. Fe overload potentiated inflammatory and lipid peroxidation processes, whereas Fe deficiency decreased them.
Assuntos
Dieta , Ácidos Graxos Insaturados/administração & dosagem , Granuloma/metabolismo , Ferro/administração & dosagem , Animais , Peso Corporal/fisiologia , Carragenina , Granuloma/induzido quimicamente , Ferro/metabolismo , Masculino , Ratos , Ratos EndogâmicosAssuntos
Ácidos Graxos Essenciais/deficiência , Granuloma/metabolismo , Deficiências de Ferro , Peroxidação de Lipídeos/efeitos dos fármacos , Animais , Ácidos Graxos Essenciais/administração & dosagem , Ácidos Graxos Essenciais/farmacologia , Granuloma/etiologia , Ferro/administração & dosagem , Ferro/farmacologia , Masculino , Ratos , Ratos EndogâmicosAssuntos
Tetracloreto de Carbono/farmacologia , Ácidos Graxos Insaturados/administração & dosagem , Ferro/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Dieta , Ácidos Graxos Insaturados/metabolismo , Ferro/administração & dosagem , Fígado/metabolismo , Masculino , Ratos , Ratos EndogâmicosAssuntos
Cálcio/metabolismo , Membrana Celular/metabolismo , Dieta , Ácidos Graxos Insaturados/administração & dosagem , Lipídeos/deficiência , Microssomos Hepáticos/metabolismo , Animais , Transporte Biológico Ativo , Ácidos Graxos Insaturados/metabolismo , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos EndogâmicosRESUMO
The effect of dietary essential fatty acid (EFA) deficiency on lipid composition, fluidity and important enzyme and transport activities of liver microsomal membrane was studied in weanling rats. After 133 d of EFA deficiency, no difference was noticed in membrane phospholipid, cholesterol and protein levels, but a significant change occurred in the fatty acid composition of bilayer phospholipids. In EFA-deficient rats, linoleic (18:2(n-6] and arachidonic (20:4(n-6] acids were both severely lower while oleic (18:1(n-9], palmitoleic (16:1(n-7] and particularly 5,8,11-eicosatrienoic (20:3(n-9] acids were significantly higher than in controls. The higher level of the latter tended to compensate for the lower level of 20:4(n-6). Membrane fluidity, as estimated by the reciprocal of the order parameter S, was lower in the deficient rats than in the controls, and all the measured microsomal enzyme activities were markedly affected. NADH-Cyt b5 electron transferring system, coupled with the fatty acid desaturation system, was higher than in controls. In contrast, the cytochrome P450 complex activity was lower and some of the important liver detoxifying enzyme activities were lower due to physical-chemical changes in the microsomal membrane. Calcium uptake and Ca2+-ATPase activity were also significantly lower in EFA-deficient rats than in controls. It was concluded that fatty acid composition may be the major factor contributing to membrane fluidity and function and that EFA might play a role in regulating the intrinsic membrane protein activities.
Assuntos
Ácidos Graxos Essenciais/deficiência , Membranas Intracelulares/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Peso Corporal , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Fluidez de Membrana , Lipídeos de Membrana/metabolismo , Fosfolipídeos/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Changes in the activity of liver microsomal Ca2+-ATPase were studied in the presence of two series of lipophilic compounds: four flavouring substances derived from methoxybenzene and four n-aliphatic alcohols. With each compound the activity was stimulated at lower concentrations and inhibited at higher concentrations. The linear relationship between equiactive concentrations of the compounds and their partition coefficients showed that the enzyme activity was modulated by perturbation of membrane hydrophobic interactions. Measurements carried out by electron-spin resonance (ESR) showed evidence of a decrease in the membrane order induced by these compounds. However, results obtained with the methoxybenzene derivatives showed that the modification in ATPase activity cannot be directly related to the decrease in membrane order. This decrease did not only reflect perturbation of hydrophobic interactions.
Assuntos
Álcoois/farmacologia , Derivados de Benzeno/farmacologia , ATPases Transportadoras de Cálcio/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Animais , Espectroscopia de Ressonância de Spin Eletrônica , Técnicas In Vitro , Masculino , Microssomos Hepáticos/enzimologia , Ratos , Ratos EndogâmicosAssuntos
Tetracloreto de Carbono/metabolismo , Feto/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Biotransformação , Cálcio/metabolismo , Sistema Enzimático do Citocromo P-450/análise , Espectroscopia de Ressonância de Spin Eletrônica , Feminino , Feto/efeitos dos fármacos , Radicais Livres , Técnicas In Vitro , Peróxidos Lipídicos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , NADP/metabolismo , Gravidez , Ratos , Ratos EndogâmicosRESUMO
The importance of the hydrophobic effect of exogenous substances and of modifications of membrane order on D-glucose uptake are still poorly defined. Our results show that the concentrative Na+ -coupled D-glucose uptake of rat enterocyte brush border membrane vesicles is inhibited by N-phenylcarbamates increase the membrane order. However, since the concentrations required for membrane order increase are much greater than those active on D-glucose uptake, the effects on lipid order cannot be responsible for the inhibition of D-glucose uptake. Measurements of D-glucose uptake under conditions of Na+ equilibrium show that these carbamates do not act directly on the carrier but indirectly by favouring the dissipation of the Na+ gradient.
Assuntos
Carbamatos/farmacologia , Glucose/metabolismo , Intestino Delgado/metabolismo , Bicamadas Lipídicas , Fenilcarbamatos , Sódio/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Clorprofam/farmacologia , Intestino Delgado/efeitos dos fármacos , Cinética , Fluidez de Membrana/efeitos dos fármacos , Microvilosidades/metabolismo , RatosRESUMO
The purpose of the present work is to establish to what extent the calcium uptake of foetal liver microsomes can be modified, as in the adult, by classical hepatotoxins. The administration of liver toxins (BrCCl3, CCl4) to the pregnant rat or their addition to foetal and maternal liver microsome preparations causes a decrease in the level of cytochrome P-450 and a drop in the calcium storage capacity of microsomes. Lipid peroxidation of membrane phospholipids is observed in the mother but not in the foetus. On the 20th day of gestation, the foetal liver shows cytochrome P-450 dependent metabolic activity and constitutes a good model illustrating the hypothesis of calcium pump inhibition by .CCl3 radicals without lipoperoxidation.
Assuntos
Bromotriclorometano/toxicidade , Cálcio/metabolismo , Tetracloreto de Carbono/toxicidade , Clorofórmio/análogos & derivados , Feto/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/análise , Feminino , Peróxidos Lipídicos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Gravidez , Ratos , Ratos EndogâmicosRESUMO
The aim of our work is to show the importance of the role of hydrophobic bonds in maintaining Mg2+-ATPase or sucrase activity and Na+-coupled D-glucose uptake normal for the brush border of rat enterocytes. The activity of the two enzymes and the D-glucose uptake were therefore measured under the action of n-aliphatic alcohols and related to the fluidity determined by ESR. Three concentrations were used for the first eight alcohols, those of octanol being about 1500-times lower than those of methanol. For each alcohol the D-glucose uptake and the fluidity were linear functions of the logarithm of the concentration, the linear regressions being practically parallel and equidistant. The concentrations (C) of the eight alcohols inhibiting the D-glucose uptake by 80% were similar to those increasing the membrane fluidity by 3%. The linear relationship which existed in both cases between log 1/C and log P, P being octanol/water partition coefficients of the alcohols, was evidence of great sensitivity to the hydrophobic effect of the alcohols. Only the first alcohols, however, produced any notable inhibition of Mg2+-ATPase and sucrase. Hydrophobic bonds are thus shown to have little influence in maintaining the activity of Mg2+-ATPase and sucrase, but they modulate the Na+-coupled D-glucose uptake.
Assuntos
Adenosina Trifosfatases/metabolismo , Álcoois/farmacologia , Glucose/metabolismo , Intestino Delgado/ultraestrutura , Sódio/metabolismo , Sacarase/metabolismo , Animais , ATPase de Ca(2+) e Mg(2+) , Espectroscopia de Ressonância de Spin Eletrônica , Masculino , Fluidez de Membrana/efeitos dos fármacos , Microvilosidades/enzimologia , Ratos , Ratos EndogâmicosAssuntos
Cálcio/metabolismo , Fígado/crescimento & desenvolvimento , Microssomos Hepáticos/metabolismo , Animais , Bromotriclorometano/farmacologia , Feminino , Compostos Ferrosos/farmacologia , Malondialdeído/biossíntese , Microssomos Hepáticos/efeitos dos fármacos , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Oxythioquinox, administered in solution in the dietary lipids at 400 mg/kg fresh food for 21 days, caused liver hypertrophy with severe steatosis. The levels of liver triglycerides increased 40-fold, phospholipids 2-fold and cholesterol 7-fold respectively. The steatosis was thought to be due to the effect of oxythioquinox on cell energy metabolism. The results demonstrate the variation of oxythioquinox toxicity with its degree of solubilisation in the vehicle of administration.
Assuntos
Fígado Gorduroso/induzido quimicamente , Fungicidas Industriais/toxicidade , Quinoxalinas/toxicidade , Animais , Hepatomegalia/induzido quimicamente , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos Endogâmicos , Vitaminas/farmacologiaRESUMO
The blood kinetics of carbaryl were followed over 24 h after oral administration of 14C-carbaryl at 20 mg kg (0.17 mu Ci mg-1) in control animals and in animals with an altered liver function (70% hepatectomy or tranylcypromine treatment). The variations in the primary toxicity of carbaryl were assessed by measuring the inhibition of the plasma and erythrocyte cholinesterases and by evaluation of the lethal doses. The 14C radioactivity in the blood and, in parallel, cholinesterase inhibition were maintained at a higher level in animals with an altered hepatic function. A study of acute toxicity also showed a decrease of the LD50 (91 mg kg-1 with tranylcypromine, 342 mg kg-1 in the hepatectomized group) in the treated animals, with respect to the controls (585 mg kg-1). In all cases, tranylcypromine had a greater effect on blood kinetics, cholinesterase inhibition and LD50 than did 70% hepatectomy.
Assuntos
Carbaril/toxicidade , Animais , Carbaril/sangue , Inibidores da Colinesterase/sangue , Feminino , Hepatectomia , Cinética , Dose Letal Mediana , Ratos , Ratos Endogâmicos , Tranilcipromina/farmacologiaRESUMO
The blood kinetics of carbaryl and the inhibition of plasma acetylcholinesterases were followed for 24 h after administration of 20 mg/kg [14C]carbaryl (0.17 microCi/mg). The kinetics of the radioactivity attributed to unaltered carbaryl is bi-exponential whereas that of the total 14C activity is tri-exponential. The kinetics were treated with open 2- and 3-compartment models respectively. The exchange rate constants between the various compartments as well as the elimination constant (expressed in h-1) were found to be: k12 = 1.93, k21 = 1.18 and k10 = 2.46 (2-compartment model) and k'12 = 18.65, k'21 = 13.90, k'13 = 1.14 k'31 = 0.125 and k'10 = 0.672 (3-compartment model). The 3-compartment model demonstrates the persistence in the blood of 14C activity which correlated with plasma acetylcholinesterase inhibition.