RESUMEN
The modulatory effect of browned yam flour diet, a dietary, staple in south-western Nigeria, on carbon tetrachloride (CCl4)-mediated lipid peroxidation and on the activities of liver microsomal and cytosolic enzymes was studied in male rats. Browned yam flour diet fed at the level of 25% and 50% to rats for 5 weeks significantly reduced the lipid peroxidation induced by CCl4 (0.5 ml/kg/wk) administered two weeks after starting the animals with the diets. The diets elicited 62% and 79% reductions in CCl4-mediated peroxidation, respectively, in the absence of exogenously added oxidants. The activities of microsomal aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), pentoxyresorufin-O-dealkylase (PROD) and cytosolic GSH S-transferase (GST) were increased when rats were fed the 25% or 50% browned yam flour diets. Browned yam flour fed at the level of 25% to rats decreased the CCl4-mediated reduction in the activities of microsomal AH, APD, PROD and GST by 64%, 28%, 58% and 25%, respectively, and by 82%, 48%, 83% and 55% when rats were fed with 50% of the diet. The results suggest that browned yam flour diet could protect against chemically-mediated lipid peroxidation and tissue damage possibly by scavenging chemically generated reactive species and enhancing carcinogen-detoxifying system.
Asunto(s)
Intoxicación por Tetracloruro de Carbono/dietoterapia , Intoxicación por Tetracloruro de Carbono/metabolismo , Citosol/enzimología , Modelos Animales de Enfermedad , Harina , Depuradores de Radicales Libres/uso terapéutico , Liliaceae/química , Peroxidación de Lípido/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Xenobióticos/metabolismo , Xenobióticos/envenenamiento , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Citocromo P-450 CYP2B1/análisis , Citosol/química , Evaluación Preclínica de Medicamentos , Glutatión Transferasa/análisis , Masculino , Microsomas Hepáticos/química , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Aniline hydroxylase from liver microsomes of rainbow trout Salmo gairdneri converted aniline to p-aminophenol, the specific activity being 0.068 nmoles/min/mg protein in potassium phosphate buffer, pH 7.4 at 25 degrees C. The maximal rate of the enzyme reaction was found at aniline concentrations above 5 mM and in the presence of NADPH. Vmax and K(m) were 0.048 nmoles/min/mg and 0.105 mM respectively. The Hill plot showed the Hill constant to be 1.02 indicating one substrate binding site with no cooperativity. Ca2+ and Mg2+ at concentrations ranging between 1-10 mM stimulated the enzyme activity.
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Anilina Hidroxilasa/análisis , Microsomas Hepáticos/enzimología , Animales , Oncorhynchus mykissRESUMEN
Five days after the induction of acute systemic inflammation in greyhounds by intramuscular and subcutaneous injections of Freund's adjuvant, the hepatic concentrations of cytochromes P-450 and b5, the activities of the hepatic microsomal enzymes aniline p-hydroxylase and aminopyrine n-demethylase and the disposition and urinary excretion of phenylbutazone were determined. The mean plasma concentrations of phenylbutazone after intravenous administration were described by the bi-exponential equations: Cp = 144.2e-34.6t + 171.5e-0.104t for five normal greyhounds and Cp = 113.6e-16.13t + 163.1e-0.108t for five febrile greyhounds. The elimination half-lives, total body clearances and apparent volumes of distribution were 6.7 hours, 18.4 ml kg-1 hour-1 and 0.18 litre kg-1, for the normal greyhounds, and 6.4 hours, 19.5 ml kg-1 hour-1 and 0.18 litre kg-1, for the febrile greyhounds. There were no significant differences between the pharmacokinetic parameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydroxyphenylbutazone excreted in the urine. In the febrile greyhounds, there were significant decreases in the hepatic microsomal concentrations of cytochromes P-450 and b5 and in the activities of aniline p-hydroxylase and aminopyrine n-demethylase.
Asunto(s)
Antiinflamatorios no Esteroideos/orina , Enfermedades de los Perros/orina , Perros/orina , Fiebre/veterinaria , Fenilbutazona/orina , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Sistema Enzimático del Citocromo P-450/análisis , Enfermedades de los Perros/tratamiento farmacológico , Perros/metabolismo , Femenino , Fiebre/tratamiento farmacológico , Fiebre/orina , Adyuvante de Freund/uso terapéutico , Masculino , Microsomas Hepáticos/enzimología , Oxifenilbutazona/orina , Fenilbutazona/sangre , Fenilbutazona/farmacocinética , Distribución AleatoriaRESUMEN
The vitamin C activity of erythorbic acid (ErA) in ascorbic acid (AsA)-deficient guinea pigs was evaluated. The guinea pigs depleted AsA for 16 days were divided into two groups: one group (control group) was supplemented with 1, 5, or 100 mg/day AsA and the other group (experimental group) was supplemented with 1, 5, 20, or 100 mg/day ErA for 4 days. The contents of AsA and ErA in the tissues of guinea pigs were determined by using HPLC, and the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 were measured. The AsA tissue content of AsA-supplemented guinea pigs was much higher than the ErA tissue content of ErA-supplemented ones, and also, the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 of AsA-supplemented animals were much higher than those of ErA-supplemented animals, even when the supplemented amount of ErA was equal to that of AsA. Based on these results, the vitamin C activity of ErA seems to be much lower than that of AsA in the AsA-deficient guinea pigs. This suggested that the apparent vitamin C activity of ErA was dependent on the AsA tissue levels of guinea pigs.
Asunto(s)
Deficiencia de Ácido Ascórbico/tratamiento farmacológico , Ácido Ascórbico/uso terapéutico , Glándulas Suprarrenales/metabolismo , Fosfatasa Alcalina/sangre , Anilina Hidroxilasa/análisis , Animales , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/fisiología , Deficiencia de Ácido Ascórbico/metabolismo , Deficiencia de Ácido Ascórbico/fisiopatología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Cromatografía Líquida de Alta Presión , Sistema Enzimático del Citocromo P-450/análisis , Cobayas , Hígado/enzimología , Hígado/metabolismo , Masculino , EstereoisomerismoRESUMEN
Studies were carried out to evaluate and relate the rate of alteration in mixed-function oxidase system with the changes of the fatty acid composition of rat microsomes induced by different dietary lipids. Male weanling rats were fed from day 21 to 120 with a commercial rat diet or a semisynthetic diet containing no fat or 10% fat consisting of peanut-rapeseed oil, sunflower oil, or salmon oil. In rats fed a fat-free diet, the cytochrome P-450 concentration and aniline hydroxylase, aminopyrine N-demethylase, and NADPH-cytochrome-c reductase activities of liver microsomes at 120 days were, respectively, 26, 16, 10, and 24% lesser than those of rats fed the control diet. However, cytochrome b5 concentration and NADH-cytochrome-b5 reductase activity were, respectively, 33 and 43% higher than those of the control group at the same time. When rats were fed the sunflower oil diet, the cytochrome P-450 concentration and NADH-cytochrome-b5 reductase activity at 120 days were, respectively, 11 and 23% lesser than those of control group. But the cytochrome b5 concentration was 10% higher than that of the control group. In rats fed the fish oil diet, the cytochrome P-450 concentration and NADPH-cytochrome-c reductase, aniline hydroxylase, and aminopyrine N-demethylase activities at 120 days were, respectively, 30, 48, 41, and 31% higher than those of rats fed the control diet. These enzymes were correlated very well (0.84 < r < 0.93), P < 0.05 with dietary sigma polyunsaturated fatty acids (n-3).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Grasas de la Dieta/metabolismo , Ácidos Grasos/análisis , Microsomas Hepáticos/química , Microsomas Hepáticos/enzimología , Oxigenasas de Función Mixta/análisis , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Sistema Enzimático del Citocromo P-450/análisis , Reductasas del Citocromo/análisis , Citocromo-B(5) Reductasa , Citocromos b5/análisis , Aceites de Pescado/metabolismo , Masculino , NADPH-Ferrihemoproteína Reductasa/análisis , Aceites de Plantas/metabolismo , Ratas , Ratas Sprague-Dawley , DesteteRESUMEN
In the experiment, the age peculiarities of the detoxication system of the liver in burn disease and the effect of enterosgel on them were studied. Decrease in hydroxylase and demethylase activity of hepatic microsomes in relatively stable activity of oxidoreductase as well as increase in activity of aminotransferases, especially that of alanine aminotransferase, which was more pronounced in aged animals, was noted. Under the influence of enterosorption, the increase in functional activity of monooxygenase system of the liver and stabilization of hepatocytic membranes are more pronounced in young animals. This contributed to reduction in lethality, activation of natural mechanisms of detoxication and reparative processes.
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Quemaduras/fisiopatología , Quemaduras/terapia , Desintoxicación por Sorción , Factores de Edad , Alanina Transaminasa/análisis , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Quemaduras/enzimología , Quemaduras/patología , Membrana Celular , Sistema Enzimático del Citocromo P-450/análisis , Femenino , Geles/uso terapéutico , Pruebas de Función Hepática , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/ultraestructura , Oxidación-Reducción , RatasRESUMEN
Desert sheep experimentally or naturally infected with Fasciola gigantica were used to study the influence of infection on the activities of some drug-metabolizing enzymes found in the liver. The enzymes investigated were aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase. The experimental infection was confirmed histologically by detection of Fasciola eggs in faeces and by measuring the activities of sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Liver specimens from naturally infected sheep were obtained from the slaughter house. The activities of aminopyrine N-demethylase and aniline 4-hydroxylase were significantly decreased in sheep either naturally infected or during the acute stage of experimental fascioliasis (killed 5 weeks post-infection). The activity of UDP-glucuronyltransferase was decreased in naturally infected sheep and those killed 9 or 13 weeks post-experimental infection.
Asunto(s)
Fascioliasis/veterinaria , Hígado/enzimología , Enfermedades de las Ovejas/enzimología , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Fascioliasis/enzimología , Glucuronosiltransferasa/análisis , OvinosRESUMEN
Gossypol, a polyphenolic pigment found in cotton plants, has been implicated as an antifertility agent. This pigment has been shown to alter myriad metabolic pathways. The objective of this study was to determine the effect of gossypol acetic acid on the hepatic microsomal drug metabolizing enzyme system in adult female Fisher 344 rats. Subcutaneous administration in both low (15 mg/kg) and high (30 mg/kg) doses of gossypol acetic acid for five consecutive days significantly (P less than 0.00001) reduced hepatic aniline hydroxylase activity, as well as cytochrome P-450 and b5 levels. Thus, compared to the controls, the low doses of gossypol decreased the hepatic aniline hydroxylase activity and cytochrome P-450 and b5 content by 73, 54, and 43 percent, respectively. The high doses of gossypol decreased the aniline hydroxylase, cytochrome P-450, and b5 levels by 60, 51, and 46 percent, respectively, as compared to controls. These data indicate that alteration of the hepatic metabolizing system may, in part, be responsible for the secondary toxemic effects seen when gossypol is used to provide antifertility action.
Asunto(s)
Gosipol/farmacología , Hígado/efectos de los fármacos , Anilina Hidroxilasa/análisis , Animales , Peso Corporal/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/análisis , Citocromos b5/análisis , Relación Dosis-Respuesta a Droga , Femenino , Gosipol/efectos adversos , Inyecciones Subcutáneas , Hígado/anatomía & histología , Hígado/metabolismo , Microsomas/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344RESUMEN
Quail were fed monensin to determine liver damage, as measured by changes in activities of serum enzymes and liver microsomal enzymes. Monensin fed at a therapeutic level of 110 ppm for 2 weeks produced an increase in cytochrome P-450 and cytochrome b5 and induction of the activities of benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, with no changes in the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). On the other hand, quail fed 110 ppm, 220 ppm, and 330 ppm monensin in feed for 6 weeks showed a significant rise in SDH and AST activities at 330 ppm but not at 110 ppm and 220 ppm. The manifestations of liver toxicity observed at 330 ppm were accompanied by a significant decrease in all the aforementioned hepatic microsomal mixed-function oxidases. In contrast, quail fed monensin at 110 ppm and 220 ppm for 6 weeks produced no change in these parameters except for benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, which were significantly increased in birds fed 220 ppm of monensin.
Asunto(s)
Colinus/metabolismo , Hígado/efectos de los fármacos , Monensina/toxicidad , Administración Oral , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Sistema Enzimático del Citocromo P-450/análisis , Citocromos b5/análisis , Relación Dosis-Respuesta a Droga , Hígado/enzimología , Masculino , Microsomas Hepáticos/química , Monensina/administración & dosificación , Oxidorreductasas N-Desmetilantes/análisisRESUMEN
Microsomes from male rats treated with picloram (100 mg/kg/day) for 7 days showed a 48% decrease in 16 alpha-hydroxylase activity when incubated with (4-14C) androstenedione. These data are consistent with the assertion that picloram decreases the titer of hepatic male specific cytochrome P-450h. Several lines of evidence suggested that picloram is an inducer of hepatic cytochrome P-450 in male rats. First, SDS polyacrylamide gel electrophoresis revealed an intensified hepatic microsomal polypeptide (MW 54,000) following picloram pretreatment. This polypeptide co-migrated with protein bands which were correspondingly intensified after pretreatment with known inducers of cytochrome P-450d (3-methylcholanthrene and isosafrole). Second, no increase in the binding of metyrapone to picloram treated microsomes was noted compared with controls, suggesting no increase in phenobarbital-inducible forms of cytochrome P-450. Third, hepatic microsomes from picloram treated rats activated 2-amino-3-methylimidazo [4,5-f] quinoline (a cytochrome P-450d mediated catalysis) causing a 5-fold increase in the number of induced Salmonella typhimurium TA98 revertant colonies formed compared with control microsomes. Fourth, the binding of n-octylamine to hepatic microsomes from picloram-treated rats showed, like microsomes from 3-methylcholanthrene-treated rats, an increase in the proportion of high-spin cytochrome P-450 present. Cytochrome P-450d is known to be a high spin haemoprotein.
Asunto(s)
Sistema Enzimático del Citocromo P-450/análisis , Isoenzimas/análisis , Hígado/enzimología , Picloram/farmacología , Ácidos Picolínicos/farmacología , Androstenodiona/metabolismo , Anilina Hidroxilasa/análisis , Animales , Electroforesis en Gel de Poliacrilamida , Femenino , Masculino , Metirapona/metabolismo , Peso Molecular , Mutágenos/metabolismo , Quinolinas/metabolismo , Ratas , Ratas Endogámicas , Factores SexualesRESUMEN
Hepatic microsomal cytochrome P-450j has been studied using the male spontaneously diabetic BB rat as a model for insulin-dependent diabetes. This approach avoids any direct hepatotoxic effects from chemical diabetogenic agents. Both diabetic rats maintained on insulin and nondiabetic littermates were used as controls. Levels of cytochrome P-450j were increased approximately 3-fold in the diabetics 4 days after the cessation of insulin therapy. In addition, cytochrome P-450j-catalyzed enzymatic activities, aniline hydroxylation, and N-nitrosodimethylamine N-demethylation were increased by the diabetic state at this same time period. Cytochrome P-450f remained at control levels in all groups of animals. In order to test the hypothesis that ketone bodies are involved in the increase in cytochrome P-450j in the diabetic state, plasma beta-hydroxybutyrate levels were monitored. Hepatic aniline hydroxylation, N-nitrosodimethylamine N-demethylation, and cytochrome P-450j levels in individual animals were found to correlate with plasma beta-hydroxybutyrate levels (r = 0.59-0.71 p less than 0.001). In contrast, no significant correlation between levels of cytochrome P-450j and plasma glucose, insulin, or cholesterol was observed in individual animals (r = 0.07-0.23, p greater than 0.4). We conclude that cytochrome P-450j is induced in the livers of spontaneously diabetic rats, and that this induction may be associated directly or indirectly with elevated plasma ketone levels.
Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , Diabetes Mellitus Experimental/enzimología , Hígado/enzimología , Ácido 3-Hidroxibutírico , Anilina Hidroxilasa/análisis , Animales , Dimetilnitrosamina/metabolismo , Inducción Enzimática , Hidroxibutiratos/sangre , Insulina/farmacología , Masculino , RatasRESUMEN
The developmental biology of superoxide dismutase and aniline hydroxylase was followed in rat lungs from prenatal stage to 3 months old. Total superoxide dismutase activity as determined by spectrophotometry as well as electrophoresis was high in the prenatal rat lung, decreased in the first 24 hr postpartum, increased within 7 days, and then decreased gradually to adult levels. On polyacrylamide gel electrophoresis only two isozymic forms of superoxide dismutase were located as achromatic zones in the fetal lung. In the adult rat lung, there were three molecular forms of superoxide dismutase, two in the postmitochondrial supernatant and one in the mitochondrial fraction. Unlike superoxide dismutase, aniline hydroxylase was detectable only after 5 days of age and the activity exhibited a gradual increase afterward up to 1 month of age. The developmental pattern of superoxide dismutase and aniline hydroxylase activities in lung may be significant in understanding the mechanism of body defenses and their regulatory modulations in response to toxic air pollutants and environmental stress.
Asunto(s)
Anilina Hidroxilasa/análisis , Animales Recién Nacidos/metabolismo , Hidrocarburo de Aril Hidroxilasas/análisis , Feto/enzimología , Pulmón/enzimología , Superóxido Dismutasa/análisis , Animales , Radicales Libres , Isoenzimas/análisis , Ratas , Superóxidos/metabolismoAsunto(s)
Diabetes Mellitus Experimental/metabolismo , Hígado/metabolismo , Preparaciones Farmacéuticas/metabolismo , Anilina Hidroxilasa/análisis , Animales , Benzopireno Hidroxilasa/análisis , Sistema Enzimático del Citocromo P-450/análisis , Masculino , NADPH-Ferrihemoproteína Reductasa/análisis , ConejosRESUMEN
The mutagenic potential of seven carcinogenic N-nitrosopropylamines was examined by means of Ames' preincubation assay using liver 9000 g superanatant (S9) fractions from rats, hamsters, mice, rabbits, monkeys and humans for metabolic activation. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), N-nitrosobis(2-oxopropyl)amine (BOP), N-nitrosobis(2-acetoxypropyl)amine (BAP), N-nitroso-2,6-dimethylmorpholine, N-nitrosomethyl(2-hydroxypropyl)amine (MHP) and N-nitrosomethyl(2-oxopropyl)amine all showed positive mutagenicity in strain TA100 in the presence of liver S9 from each of the uninduced animals, but N-nitrosobis(2-hydroxypropyl)amine was negative. The mutagenic activity of MHP was highest with liver S9 from the hamster, but that of BAP was lowest with hamster liver S9. With regard to the activities of the other N-nitrosopropylamines, there were no significant differences among five animal species. In the presence of liver S9 from humans, HPOP, BOP and MHP showed positive mutagenicity. With the exception of HPOP and BOP, the animal or human liver S9-mediated mutagenicity of these N-nitrosopropylamines was almost completely lost upon removal of NADP+ from the assay system, preincubation in an atmosphere of carbon monoxide, or addition of cytochrome c to the S9 mixture. metyrapone decreased the activities of five compounds (except for BOP) by between 29 and 71%, whereas 7,8-benzoflavone was totally lacking in this effect. These results demonstrated that the phenobarbital-inducible major cytochrome P-450 in animal and human livers is involved in the mutagenic activation of the N-nitrosopropylamines.
Asunto(s)
Carcinógenos/metabolismo , Sistema Enzimático del Citocromo P-450/fisiología , Hígado/metabolismo , Mutágenos/metabolismo , Nitrosaminas/metabolismo , Adulto , Anilina Hidroxilasa/análisis , Animales , Benzoflavonas/farmacología , Biotransformación , Cricetinae , Citocromo P-450 CYP1A2 , Citocromos/fisiología , ADN/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Macaca fascicularis , Macaca mulatta , Masculino , Mesocricetus , Metilación , Metilcolantreno/farmacología , Metirapona/farmacología , Ratones , Ratones Endogámicos , Fenobarbital/farmacología , Conejos , Ratas , Ratas Endogámicas , Especificidad de la EspecieAsunto(s)
Amoníaco/toxicidad , Microsomas Hepáticos/efectos de los fármacos , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Peso Corporal/efectos de los fármacos , Hexobarbital/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Microsomas Hepáticos/enzimología , Sueño/efectos de los fármacosRESUMEN
Male Donryu rats and B6C3F1 mice were treated with dietary 3-methoxy-4-aminoazobenzene (3-MeO-AAB) (0.06% or 0.09%), and subcellular fractions of the liver were examined for ability to mutagenically activate 3-MeO-AAB and 2 amino acid pyrolysate components using Salmonella typhimurium TA 98 as a tester strain. The treatment resulted in striking induction of enzyme(s) for the mutagenic activation of these aromatic amines in rats, but the effect was smaller in mice. The enzyme(s) involved in the reaction was characterized as an isotype of microsomal cytochrome P-448.
Asunto(s)
Compuestos Azo/metabolismo , Carcinógenos/metabolismo , Mutágenos/metabolismo , p-Aminoazobenceno/metabolismo , Aminopirina N-Demetilasa/análisis , Anilina Hidroxilasa/análisis , Animales , Biotransformación , Peso Corporal/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/análisis , Inducción Enzimática/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos , Tamaño de los Órganos/efectos de los fármacos , Ratas , Especificidad de la Especie , p-Aminoazobenceno/toxicidadRESUMEN
The influence of age on hepatic microsomal drug metabolism was determined in male and female Syrian hamsters fed purified diet or commercial ration. Data from hamsters are reported on hepatic contents of microsomal protein and cytochrome P450, as well as activities of arylhydrocarbon hydroxylase and aniline hydroxylase measured at 4, 10, 22, 34, and 64 weeks of age. Hepatic microsomal protein increased at 34 and 64 weeks in hamsters fed purified diet and at 64 weeks in those fed commercial diet. Cytochrome P450 liver content, based on microsomal protein, was highest at 10 weeks in hamsters given purified diets. Peak values were less with the commercial diet and did not differ between 10, 22, and 34 weeks. When expressed on a body weight basis, cytochrome P450 values increased between 4 and 10 weeks in all groups, except in males fed purified diet, in which values increased up to 34 weeks. Arylhydrocarbon hydroxylase activity increased between 4 and 10, 22 or 34 weeks and declined by 64 weeks in every group when based on microsomal protein content or body weight. Aniline hydroxylase activity, based on microsomal protein, increased between 4 and 10 or 22 weeks and then declined by 64 weeks in every group, except in females fed commercial diet, in which no increase occurred. Changes in aniline hydroxylase, based on body weight, were not consistent with these patterns. Maximum values occurred at 4 weeks for females and at 22 weeks for males fed purified diet, but at 10 weeks in males given commercial diet. Declines in drug metabolism between maturity and senescence were greater when data were expressed on the basis of microsomal protein content, when compared with data on a body weight basis.
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Hígado/metabolismo , Preparaciones Farmacéuticas/metabolismo , Factores de Edad , Anilina Hidroxilasa/análisis , Animales , Hidrocarburo de Aril Hidroxilasas/análisis , Cricetinae , Sistema Enzimático del Citocromo P-450/análisis , Dieta , Femenino , Masculino , Mesocricetus , Tamaño de los Órganos , Factores SexualesRESUMEN
Adriamycin treatment in vivo or addition to incubation mixtures in vitro inhibits hepatic drug metabolism. It has been suggested that adriamycin-induced membrane lipid peroxidation may be a mechanism responsible for this activity in vitro. To determine if similar mechanisms operate in vivo, adriamycin inhibition of drug metabolism was compared in rats whose tissue lipid peroxidizability was altered by manipulating dietary levels of vitamin E. Weanling rats maintained on vitamin E deficient (0 ppm) or supplemented (10 or 100 ppm) diets for 12 weeks were given either adriamycin, 5 mg/kg/week, or equal volumes of the saline vehicle for 3 weeks intraperitoneally. Vitamin E deficiency alone (0 ppm, saline pretreatment) produced a 37% increase in hepatic lipid peroxidation without any appreciable alteration in hepatic aniline hydroxylase, ethylmorphine N-demethylase or aryl hydrocarbon hydroxylase activities. Adriamycin pretreatment altered hepatic lipid peroxidizability over corresponding saline pretreated controls dependent on dietary vitamin E. No increase was seen in the 100 ppm group, while 44% and 500% increases occurred at 10 and 0 ppm vitamin E, respectively. Adriamycin pretreatment decreased drug-metabolizing enzyme activity by an average of 32% for aniline hydroxylase, 26% for ethylmorphine N-demethylase and 63% for aryl hydrocarbon hydroxylase. Statistically, decreases in drug metabolism were independent of dietary vitamin E and did not correlate with lipid peroxidizability. These data would suggest that in vivo adriamycin-induced depression of hepatic drug-metabolizing enzymes is not mediated by elevated lipid peroxidation.
Asunto(s)
Doxorrubicina/farmacología , Peróxidos Lipídicos/metabolismo , Hígado/efectos de los fármacos , Deficiencia de Vitamina E/metabolismo , Anilina Hidroxilasa/análisis , Animales , Hidrocarburo de Aril Hidroxilasas/análisis , Hígado/metabolismo , Masculino , Ratas , Ratas EndogámicasRESUMEN
The mutagenic activities of N-nitrosobis(2-hydroxypropyl)amine (BHP) and its related compounds were studied in Salmonella typhimurium TA100 and TA98 strains by Ames's liquid incubation assay in the presence or absence of lung and liver S9 of rats treated with polychlorinated biphenyl (PCB). BHP and its related compounds, N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), N-nitrosobis(2-oxopropyl)amine (BOP), N-nitrosobis(2-acetoxypropyl)amine (BAP), and N-nitroso-2,6-dimethylmorpholine (NDMM) showed negative mutagenicity in the absence of lung and liver S9 in TA100 and TA98 strains while those compounds showed positive in the presence of liver S9 in TA100 strain. HPOP and BOP showed positive mutagenic activity in the presence of lung S9 in TA100 strain. HPOP showed the strongest mutagenic activity in the presence of lung and liver S9.