RESUMEN
Evidence suggests that impaired lipolysis may contribute to fat accumulation. To test whether the lipolytic response to adrenergic stimulation is lower in Pima Indians, a population prone to obesity and type 2 diabetes mellitus, than in Caucasians, 48 healthy, non-diabetic subjects were studied: 27 Pima Indians (12 males and 15 females, 30 +/- 7 yr, 85 +/- 18 kg, 36 +/- 10% body fat; mean +/- SD) and 21 Caucasians (11 males and 10 females, 34 +/- 7 yr, 105 +/- 26 kg, 39 +/- 11% body fat). Lipolysis in the abdominal s.c. adipose tissue was assessed in situ by glycerol concentration in microdialysis samples at baseline and during local infusion of the nonselective beta-adrenergic agonist isoproterenol (10(-6) mol/L), mental stress, and submaximal exercise. The baseline dialysate glycerol concentrations were similar in Pima Indians and Caucasians. Lipolytic response (relative increment in dialysate glycerol concentration, percentage above the baseline) was similar in Pima Indians and Caucasians in response to local isoproterenol infusion (77 +/- 36% and 76 +/- 40%) and exercise (38 +/- 38% and 41 +/- 41%). During mental stress, the dialysate concentration did not change significantly from baseline in either group. Changes in local blood flow, determined by ethanol dilution, did not differ between the two groups. In conclusion, the high propensity for obesity in Pima Indians does not seem to be due to an impaired lipolytic response to stimuli.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Indígenas Norteamericanos , Isoproterenol/farmacología , Lipólisis/efectos de los fármacos , Estrés Psicológico/fisiopatología , Población Blanca , Arizona , Ejercicio Físico/fisiología , Humanos , Modelos Lineales , Lipólisis/fisiología , Obesidad/fisiopatologíaRESUMEN
Hyperinsulinemia is commonly associated with obesity, but it has not been determined which defect comes first. Some have proposed that hyperinsulinemia may precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific Islanders. In contrast, longitudinal studies in adults show that insulin sensitivity and low fasting insulin concentrations are associated with increased weight gain, whereas insulin resistance seems to protect against weight gain. The present study examined whether fasting plasma hyperinsulinemia is a risk factor for weight gain in prepubertal children in the Pima Indian population-a population that is prone to obesity. Fasting plasma insulin concentration was measured in 328 5- to 9-year-old Pima Indian children (147 boys and 181 girls) with normal glucose tolerance. Follow-up weight was obtained an average of 9.3 +/- 1.9 years (means +/- SD) later at age 15-19 years. Fasting plasma insulin concentration correlated with the rate of weight gain per year in both boys (r = 0.42; P < 0.0001) and girls (r = 0.20; P < 0.01) and was associated with the rate of weight gain, independent of known determinants of weight change, i.e., initial relative weight, change in height, age, and sex. Similar relationships were found between fasting plasma insulin concentration and the change in relative weight and in triceps skinfold thickness-two indicators of obesity. In conclusion, fasting hyperinsulinemia may be a risk factor for the development of obesity in young children.
Asunto(s)
Hiperinsulinismo/sangre , Indígenas Norteamericanos/estadística & datos numéricos , Insulina/sangre , Obesidad/etiología , Aumento de Peso/fisiología , Arizona/epidemiología , Glucemia/análisis , Glucemia/metabolismo , Niño , Preescolar , Ayuno , Femenino , Estudios de Seguimiento , Humanos , Hiperinsulinismo/complicaciones , Hiperinsulinismo/metabolismo , Insulina/metabolismo , Modelos Lineales , Estudios Longitudinales , Masculino , Obesidad/epidemiología , Factores de Riesgo , Grosor de los Pliegues CutáneosRESUMEN
A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta 3-adrenoceptor variant, and/or indicate that the beta 3-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis.
Asunto(s)
Tejido Adiposo/metabolismo , Arginina , Variación Genética , Indígenas Norteamericanos/genética , Isoproterenol/farmacología , Lipólisis , Mutación Puntual , Receptores Adrenérgicos beta/genética , Triptófano , Tejido Adiposo/irrigación sanguínea , Tejido Adiposo/efectos de los fármacos , Adulto , Arizona , Glucemia/metabolismo , Índice de Masa Corporal , Femenino , Glicerol/análisis , Glicerol/sangre , Homocigoto , Humanos , Insulina/sangre , Lipólisis/efectos de los fármacos , Masculino , Microdiálisis , Receptores Adrenérgicos beta 3 , Valores de Referencia , Flujo Sanguíneo Regional/efectos de los fármacos , PielRESUMEN
We discuss evidence indicating how ethanol could generate oxygen free radicals. Recent use of techniques such as spin trapping and EPR spectroscopy have demonstrably confirmed that both acute and chronic alcohol use by laboratory animals would generate free radical intermediates. These radicals are of biological origin and presumably involve lipids. However, an exact identification of the intermediates produced has not been worked out with the currently available methodologies. Also not known is the mechanism whereby ethanol could initiate free radicals. The relationship between generation of free radicals and cell toxicity or carcinogenesis is also not understood. Using a variety of systems that included different species, strains and gender (male Sprague-Dawley and Fisher-344 rats, female C57BL/6 mice, male Syrian golden hamsters) and carcinogens (NMBZA, NNN, NNK, DMBA and LP-BM5 retrovirus) we have shown an association of lipid peroxidation with ethanol tumor promotionability. However, the process of tumor promotion in general is not very clear and the role played by ethanol in this process is still more unclear. Here we are reviewing evidence that could possibly be involved in such promotion processes.
Asunto(s)
Etanol/efectos adversos , Etanol/farmacología , Neoplasias/etiología , Oxígeno/metabolismo , Animales , Carcinógenos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Etanol/metabolismo , Femenino , Radicales Libres/metabolismo , Humanos , Quelantes del Hierro/metabolismo , Peroxidación de Lípido , Masculino , Mitocondrias Hepáticas/metabolismo , NADP/metabolismo , Neoplasias/metabolismo , Xantina Deshidrogenasa/metabolismoRESUMEN
The contribution of moderate ethanol consumption on cocaine induced hepatotoxicity and the role lipid peroxidation plays as a possible mechanism of such increased hepatotoxicity were evaluated. Male C57BL/6 mice were injected interperitoneally (i.p.) with increasing doses of cocaine, from 10 to 50 mg/kg body weight daily and simultaneously fed a liquid diet containing 28% of the calories as ethanol for 5 or 9 weeks. Control mice received saline (i.p.) and an isocaloric carbohydrate diet. Lipid fluorescence and conjugated dienes of extracted lipids and amounts of malondialdehyde (MDA) were evaluated as indices of lipoperoxidation. In addition, serum alanine aminotransferase and aspartate transaminase were measured as indicators of liver injury and cellular death. After 9 weeks, ethanol consumption during cocaine treatment increased hepatic lipid fluorescence, conjugated dienes and MDA about twofold over mice-treated with cocaine alone. Similarly, serum transaminases were 2.8-6-fold greater in mice consuming alcohol and treated with cocaine than in mice treated with cocaine only. Histological examination of livers from mice fed ethanol during treatment with cocaine exhibited increased hepatic injuries and necrosis. The data suggest that ethanol exacerbates cocaine-induced hepatotoxicity via increases in free radical activity and hepatic lipid peroxidation.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cocaína/toxicidad , Etanol/toxicidad , Hepatitis Alcohólica/patología , Animales , Cocaína/farmacocinética , Sinergismo Farmacológico , Etanol/farmacocinética , Peroxidación de Lípido/efectos de los fármacos , Hígado/patología , Pruebas de Función Hepática , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosfolípidos/metabolismoRESUMEN
Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged with N-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Alcoholismo/fisiopatología , División Celular/efectos de los fármacos , Transformación Celular Neoplásica/inducido químicamente , Neoplasias Esofágicas/inducido químicamente , Vitamina E/fisiología , Consumo de Bebidas Alcohólicas/fisiopatología , Animales , Carcinógenos , División Celular/fisiología , Cocarcinogénesis , Dimetilnitrosamina/análogos & derivados , Neoplasias Esofágicas/fisiopatología , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
Tumor appearance can be accelerated in the immunodeficient and immunosuppressed animal. The role of lipid peroxidation and immune dysfunction induced by retrovirus and ethanol treatments on cancer promotion were investigated. Following the initiation of esophageal cancer by methylbenzylnitrosamine, ethanol consumption and retrovirus infection individually and concomitantly increased growth of esophageal tumors. Dietary supplementation with vitamin E reduced the size and frequency of the developed tumors. Tumor growth modifications in the vitamin E supplemented animals may be due to changes in T-cell numbers and functions stimulated by vitamin E. In addition, increased production of free radicals following ethanol treatment and retrovirus infection, and the suppression of these formations lipid peroxide by vitamin E is accompanied by lower incidence and size of tumors. Thus, the mechanisms of tumor enhancement observed in immunocompromised animals may include a combination of immunomodulation and modification of oxidant production by ethanol consumption and retrovirus infection.
Asunto(s)
Neoplasias Esofágicas/patología , Etanol/toxicidad , Huésped Inmunocomprometido , Peroxidación de Lípido/efectos de los fármacos , Infecciones por Retroviridae/inmunología , Síndrome de Inmunodeficiencia Adquirida/metabolismo , Animales , Femenino , Radicales Libres , Ratones , Ratones Endogámicos C57BL , Vitamina E/farmacologíaRESUMEN
Retrovirally induced immunosuppression may elevate the incidence of chemically induced cancers. A proposed hypothesis to explain this relationship is the increased free radical activity observed during retroviral infection and carcinogen activation. We previously found that vitamin E retarded growth of esophageal tumors accompanied by reductions of free radical products. This study investigated the contribution that retroviral immunosuppression has on esophageal cancer induced by the carcinogen N-nitrosomethylbenzylamine (NMBzA), and the response that increased levels of dietary vitamin E has on this induced carcinogenesis. Female C57BL/6 mice received NMBzA or vehicle (corn oil) i.p. weekly for 3 weeks. Then some of the mice were infected with LP-BM5 murine retrovirus and fed diets containing 30 IU vitamin E or 172 IU vitamin E/kg of diet. As an assessment of free radical activity, exhaled ethane was measured prior to killing the animals at 26 weeks. Esophagi from the various mice groups were assessed for size and frequency of tumors. Livers homogenates were analyzed for vitamins A and E, lipid fluorescence, conjugated dienes and malondialdehyde. Hepatic levels of vitamin A and E were decreased (P < 0.05) and indices of lipid peroxidation were greater (P < 0.05) in NMBzA-treated mice relative to controls. Lipid peroxidation and serum transaminases (ALT and AST) were greatest in mice given NMBzA and infected with the retroviruses. Incidence of esophageal tumors were also greatest in the NMBzA-treated, immunocompromised animals. Mice fed vitamin E-supplemented diets showed increased (P < 0.05) hepatic concentrations of vitamin E and vitamin A, decreased activities of serum transaminases, decreased indices of lipid peroxidation, and decreased size and frequency of esophageal tumors in both the immunocompromised and non-immunocompromised mice. These results suggest that vitamin E plays an antioxidant function that retards the incidence of esophageal cancers in immunocompromised and non-immunocompromised animals.
Asunto(s)
Dimetilnitrosamina/análogos & derivados , Neoplasias Esofágicas/prevención & control , Huésped Inmunocomprometido/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Infecciones por Retroviridae/inmunología , Vitamina E/uso terapéutico , Animales , Carcinógenos , Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Esofágicas/inducido químicamente , Neoplasias Esofágicas/microbiología , Femenino , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/metabolismo , Ganglios Linfáticos/anatomía & histología , Ganglios Linfáticos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Síndrome de Inmunodeficiencia Adquirida del Murino/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Infecciones por Retroviridae/complicaciones , Bazo/anatomía & histología , Bazo/efectos de los fármacos , Vitamina A/metabolismo , Vitamina E/metabolismoAsunto(s)
Anticarcinógenos/farmacología , Carcinógenos/toxicidad , Dimetilnitrosamina/análogos & derivados , Neoplasias Esofágicas/prevención & control , Etanol/toxicidad , Vitamina E/farmacología , Animales , Dimetilnitrosamina/toxicidad , Neoplasias Esofágicas/inducido químicamente , Neoplasias Esofágicas/patología , Femenino , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Vitamina A/metabolismo , Vitamina E/metabolismoAsunto(s)
Anticarcinógenos/farmacología , Neoplasias Esofágicas/patología , Síndrome de Inmunodeficiencia Adquirida del Murino/complicaciones , Vitamina E/farmacología , Animales , Anticarcinógenos/administración & dosificación , Carcinógenos/toxicidad , Dimetilnitrosamina/análogos & derivados , Dimetilnitrosamina/toxicidad , Neoplasias Esofágicas/inducido químicamente , Neoplasias Esofágicas/prevención & control , Femenino , Alimentos Fortificados , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Vitamina E/administración & dosificaciónRESUMEN
The antitumorigenic effects of carotenoids, in addition to their immuno-enhancing effects, may occur by their direct action on growing tumor cells. To test this hypothesis the direct inhibitory effect of various concentrations of canthaxanthin (CX; 4,4'-diketo-beta-carotene), a non-provitamin A carotenoid, was tested on the in vitro growth of JB/MS, B16F10 melanomas and PYB6 fibrosarcoma and murine non-transformed NIH-3T3 (ATCC CRL 1658) cells. At concentrations of 1 x 10(-8) M up to 1 x 10(-4) M, CX significantly reduced the overall number of tumor cells. The greatest inhibition was observed at a CX concentration of 1 x 10(-4) M after 72 h and 96 h of incubation. However, CX had no inhibitory effect on the growth of the non-transformed NIH-3T3 cell line; rather it significantly enhanced growth of this cell line (P less than 0.05) after 96 h of incubation. Thus, the inhibitory action of CX on growing tumor cells appears to be due to its direct actions on tumor cells and not via its conversion to vitamin A or its immuno-enhancing effects.
Asunto(s)
Cantaxantina/farmacología , División Celular/efectos de los fármacos , Fibrosarcoma/patología , Melanoma Experimental/patología , Sarcoma Experimental/patología , 9,10-Dimetil-1,2-benzantraceno , Análisis de Varianza , Animales , Cantaxantina/uso terapéutico , Línea Celular Transformada , Células Cultivadas , Fibrosarcoma/inducido químicamente , Fibrosarcoma/tratamiento farmacológico , Melanoma Experimental/inducido químicamente , Melanoma Experimental/tratamiento farmacológico , Ratones , Sarcoma Experimental/inducido químicamente , Sarcoma Experimental/tratamiento farmacológico , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The relatively high incidence of infectious disease in alcoholics is attributed to the immunosuppressive effects of alcohol. The potential role of alcohol as cofactor in HIV infection and in the development and expression of AIDS is suggested but unknown. In order to understand better the contribution of alcohol to immune dysfunction following HIV infection, we assessed the presence of specific markers on thymus and spleen cells in C57B1/6 mice infected with LP-BM5 murine leukemia virus and fed ethanol-containing diets. In the first experiments, mice were fed diets containing 0, 4.5, 5.5, and 6% (v/v) ethanol for 14 weeks. High ethanol exposure (6%) resulted in severe dehydration and death after 7 weeks. Although moderately low intakes of ethanol did not significantly modify percentages of T and B cells, they increased the absolute number of mature T, B, and CD4+ cells and decreased percentages of Thy 1.2+ cells. In the second experiment, mice were infected with LP-BM5 murine leukemia retrovirus and fed diets containing 5% ethanol in a regimen of 5 days of ethanol diet and 2 days of diet without alcohol for 12 weeks. Ethanol exposure in the retrovirally infected mice showed a marked decrease in Thy 1.2+ (P < 0.05). Moderate decreases in percentages of CD4+, CD8+, CD5+ cells and an increase in Ia+ cells were also observed in the retrovirus/infected ethanol-treated mice. Moderate ethanol consumption during retroviral infection induced mild/moderate changes on lymphoid cells. Ethanol consumption may accelerate the progression of murine AIDS through such changes in the lymphoid cells of the spleen.
Asunto(s)
Alcoholismo/inmunología , Subgrupos de Linfocitos B/efectos de los fármacos , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Animales , Subgrupos de Linfocitos B/inmunología , Relación CD4-CD8 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Etanol/farmacocinética , Etanol/farmacología , Femenino , Recuento de Leucocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Subgrupos de Linfocitos T/inmunologíaRESUMEN
The effect of caloreen (glucose polymer) supplementation on indicators of iron status during protein-energy malnutrition was studied. Sixty-four children with moderate protein energy malnutrition (PEM) were fed diets supplemented with caloreen or starch (control) for 14 days, following which iron status as packed cell volume (PCV), haemoglobin (Hb), serum iron, total iron binding capacity (TIBC), serum ferritin, and urinary iron levels were determined. Caloreen supplementation significantly increased (P less than 0.05). PCV, serum iron and serum ferritin and decreased (P less than 0.05) TIBC. Also, there was a tendency for Hb to increase and urinary iron to decrease in this group, but these changes were not statistically significant. Such changes were not observed in the starch-placebo-supplemented group. It is concluded that caloreen supplementation to PEM children increases body iron status. These increases in the indices of iron status may contribute to an early recovery of anaemia associated with PEM. Prolonged supplementation of a regular diet with glucose early in the development of PEM may retard the development and severity of anaemia in children.
Asunto(s)
Dextrinas/farmacología , Hierro/sangre , Desnutrición Proteico-Calórica/dietoterapia , Niño , Preescolar , Dextrinas/uso terapéutico , Ferritinas/sangre , Hematócrito , Hemoglobinas/análisis , Hospitales Universitarios , Humanos , Hierro/orina , Masculino , Nigeria , Desnutrición Proteico-Calórica/sangre , Desnutrición Proteico-Calórica/orinaRESUMEN
Effects of cocaine administration on lipid peroxidation and liver damage in immunocompromised mice fed different levels of dietary proteins were investigated. Indices of lipid peroxidation and serum aminotransferases as evidence of free radical attack and liver damage were compared in mice fed a low protein (4%) or regular protein diet (20% protein) for 3 weeks and then infected with murine leukemia virus and given daily intraperitoneal injections of increasing progressive doses of 5-45 mg.kg-1.day-1 of cocaine for 11 weeks. Cocaine administration significantly increased hepatic triglycerides, serum aminotransaminases, conjugated dienes, lipid fluorescence, and malondialdehyde levels. These changes were exacerbated by retroviral infection and also by protein undernutrition. Retroviral infection additively increased indices of cocaine-induced lipid peroxidation and hepatic damage. Significant increases in indices of lipid peroxidation and greater liver injury were also detected in similarly treated mice that received the low protein diet compared with well-nourished mice. These results show that immunocompromised mice fed low levels of dietary protein form significantly increased immunogenic lipid peroxidation adducts during cocaine treatment.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Cocaína/toxicidad , Desnutrición Proteico-Calórica/complicaciones , Infecciones por Retroviridae/complicaciones , Animales , Peso Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Femenino , Virus de la Leucemia Murina , Leucemia Experimental/complicaciones , Leucemia Experimental/fisiopatología , Metabolismo de los Lípidos , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Esteatitis/inducido químicamente , Esteatitis/metabolismo , Transaminasas/sangre , Triglicéridos/metabolismoRESUMEN
The severe hepatic disorders in patients with acquired immune deficiency syndrome (AIDS) is often attributed to a variety of other factors which could affect hepatic function. To evaluate the mechanism of liver damage in murine AIDS-induced immune-suppressed animal, a murine model of AIDS (MAIDS), caused by infection with LP-BM5 murine leukemia virus was used at a late stage of the disease. Retroviral infection significantly increased hepatic cholesterol, triacylgycerol and the cholesterol/phospholipid ratio. Similarly, the proportions of palmitic, palmitoleic, linoleic, ratios of linoleic to arachidonic and saturated to unsaturated fatty acids were significantly lower while the proportion of oleic, docosatetraenoic and docosahexenoic fatty acids were significantly increased in the retrovirus infected mice. Hepatic dysfunction as evidence by increased serum transaminase levels were also observed in the retrovirus infected animals. The data suggest that the liver damage in murine AIDS is induced by retroviral infection and the desaturase enzymes system necessary to maintain regular balance of the fatty acids in the cells may be affected during retroviral infection.
Asunto(s)
Metabolismo de los Lípidos , Hígado/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Murino/metabolismo , Animales , Colesterol/metabolismo , Modelos Animales de Enfermedad , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos/metabolismo , Femenino , Hígado/enzimología , Ratones , Ratones Endogámicos C57BL , Fosfolípidos/metabolismo , Transaminasas/sangre , Triglicéridos/metabolismoRESUMEN
Promotion of chemically induced esophageal cancer by ethanol may include the generation of highly reactive free radicals and thus may be preventable by the antioxidant vitamin E. In the present study, female C57BL/6 mice received N-nitrosomethylbenzylamine (NMBzA, 0.2 mg/kg ig) three times a week for three weeks. After this esophageal carcinogenic treatment, mice were fed a nutritionally adequate liquid diet with 30% of the calories supplied by ethanol or an isocaloric carbohydrate with or without supplemental alpha-tocopherol (142 mg/kg diet). As a marker of in vivo lipid peroxidation, exhaled ethane was collected and measured 24 hours "before" the mice were killed after 20 weeks of dietary treatment. Hepatic malondialdehyde, lipid fluorescence, and conjugated dienes were determined as markers of products of lipid peroxidation and serum aminotransferases as indexes of liver toxicity. Hepatic liver concentrations of vitamins A and E and the size and frequency of esophageal tumors were also assessed. Ethanol consumption after NMBzA administration significantly increased (p less than 0.05) the size and frequency of esophageal tumors. These ethanol-promoted effects were accompanied by increases in indexes of in vivo and accumulated products of lipid peroxidation. Similarly treated animals that received supplemental dietary vitamin E showed significant reductions (p less than 0.05) in mean tumor size and frequency of tumors as well as a decrease in the indexes of hepatic lipid peroxidation. The results suggest that promotion of NMBzA-induced esophageal tumors by ethanol may in part result from increased lipid peroxidation and that vitamin E reduces carcinogenicity of NMBzA or ethanol promoter effects by inhibiting lipid peroxidation.
Asunto(s)
Anticarcinógenos/farmacología , Neoplasias Esofágicas/prevención & control , Etanol/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Vitamina E/farmacología , Animales , Peso Corporal/efectos de los fármacos , Dimetilnitrosamina/análogos & derivados , Ingestión de Alimentos/efectos de los fármacos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/inducido químicamente , Neoplasias Esofágicas/patología , Etano/análisis , Etanol/antagonistas & inhibidores , Etanol/sangre , Femenino , Radicales Libres , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/análisis , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Vitamina A/metabolismo , Vitamina E/sangreRESUMEN
The purpose of this study was to investigate the effects of vitamin E supplementation on ethanol- and cod liver oil-induced lipid peroxidation. Adult male rats received diets containing ethanol, cod liver oil and supplemented with vitamin E for 28 days. Following treatment, hepatic conjugated dienes, lipid fluorescence, and exhalation of ethane were measured as indices of lipid peroxidation. Ethane expiration over a 3-hour period was reduced by 96% in rats fed ethanol supplemented with vitamin E. Exhalation of ethane was increased by CLO feeding but was reduced 89% in the CLO-fed rats supplemented with vitamin E. In addition, ethane production was elevated in rats fed ethanol plus CLO compared to rats fed diets containing CLO supplemented with vitamin E. Supplementation of the CLO diet with vitamin E also significantly decreased hepatic conjugated fatty acid dienes levels. Levels of hepatic conjugated fatty acid dienes from rats fed ethanol plus vitamin E were reduced 91% compared to rats fed ethanol diets. Additionally, hepatic lipid fluorescence expressed as per mg of hepatic phospholipid basis was also significantly increased in rat groups fed vitamin E, ethanol, and cod liver oil diets. Where vitamin E was added to these same diets a significant decrease of hepatic lipid peroxidation products occurred. The observed reduction in lipid peroxidation by vitamin E may be useful to retard lipid peroxides derived materials involved in the development of alcoholic liver diseases.
Asunto(s)
Aceite de Hígado de Bacalao/farmacología , Etanol/farmacología , Peroxidación de Lípido/efectos de los fármacos , Vitamina E/farmacología , Animales , Etano/metabolismo , Etanol/metabolismo , Fluorescencia , Radicales Libres , Masculino , Ratas , Ratas EndogámicasRESUMEN
Mice consume high levels of alcohol for a short period of time resulting in increased toxicity and lethality. The effects of lower doses that could be consumed without death for prolonged periods were studied. The effects of moderate doses of ethanol on indices of lipid peroxidation (LP), liver lipid accumulation and hepatotoxicity were studied in C57BL/6 mice. Three groups of mice were fed diets in which ethanol provided 0, 25 or 30% of the total calories for 3, 7, 10 and 13 weeks. Increased hepatic cholesterol, phospholipid and triglycerides, indicative of changes in liver lipid metabolism; and increased levels of hepatic malondialdehyde, conjugated dienes, lipid fluorescence, serum alanine aminotransferase and minimal changes in liver architecture indicative of LP and liver damages, were observed in mice fed the alcoholic diets. Such increases were time and dose dependent. These results suggest that continuous ingestion of lower levels of dietary ethanol in mice produces biochemical and hepatotoxic responses which are indicative of the health risk often associated with high alcohol intake.
Asunto(s)
Consumo de Bebidas Alcohólicas/patología , Alcoholismo/patología , Metabolismo de los Lípidos , Hepatopatías Alcohólicas/patología , Hígado/patología , Alanina Transaminasa/metabolismo , Animales , Colesterol/metabolismo , Ácidos Grasos/metabolismo , Femenino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosfolípidos/metabolismo , Triglicéridos/metabolismoRESUMEN
Eight groups of 5 rats were fed 8 differing liquid diets with and without ethanol, cod liver oil and/or increased levels of vitamin E. Hepatic levels of vitamins A and E were determined following the 28-day feeding time. Ethanol consumption decreased the levels of hepatic vitamin E (p less than 0.05), vitamin A (p less than 0.05) and the ratio of vitamin A/E (p less than 0.05). Hepatic levels of vitamins A and E were unaffected in rats fed cod liver oil. Supplementation of the normal dietary level of 30 IU of vitamin E per kg diet, with an additional 142 IU alpha tocopherol/kg diet, restored hepatic concentrations of vitamin E to normal levels in alcohol-fed rats. The hepatic levels of vitamin A in rats fed ethanol diets supplemented with vitamin E were less than that of control rats but were 4.3 times greater than that of rats on ethanol diets unsupplemented with vitamin E. However, the vitamin A and E ratio was equal to normal in this group of rats. The vitamin A/E ratio was reduced in liver of rats fed non-alcoholic diets supplemented with vitamin E due to increased levels of hepatic vitamin E. Additionally, rats fed cod liver oil diets containing ethanol also indicated decreased hepatic vitamin A and E levels. However, these levels were greater than that of rats fed only alcoholic diets suggesting that these vitamins are replaced by the vitamin A and E content in the cod liver oil.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Alcoholismo/metabolismo , Aceite de Hígado de Bacalao/administración & dosificación , Hígado/efectos de los fármacos , Vitamina A/metabolismo , Vitamina E/administración & dosificación , Animales , Antioxidantes , Ingestión de Alimentos , Alimentos Fortificados , Peroxidación de Lípido , Hígado/metabolismo , Masculino , Ratas , Ratas Endogámicas , Vitamina E/metabolismoRESUMEN
The literature is briefly summarized as to immunologic modifications caused by the human acquired immune deficiency syndrome (AIDS), immunocompetence at various nutritional states of vitamin E, and the immunoenhancing properties of vitamin E. The abnormalities of immune components present in AIDS are similar to those that are stimulated or restored by intake of high doses of vitamin E. Dietary supplementation of vitamin E with an adequate nutrition support or concomitant use of this vitamin with current drug therapies [For example, Zidovudine (AZT)] may increase the therapeutic efficiency of drugs and enhance immune resistance to opportunistic infections associated with AIDS. Supplementation with vitamin E may also decrease the progression of the disease to AIDS. Unlike many pharmacological agents which are toxic at low levels, vitamin E is non-toxic over a wide range of intakes. A moderately high dose may be used to target and stimulate some specific immune cells destroyed by HIV infection. However, further interdisciplinary studies are much needed to relate various levels of intake of this vitamin as a supplement to clinical outcomes during HIV infection and establish the role for this vitamin in human immunity during AIDS.