Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Ácidos Grasos Esenciales/química , Ácidos Grasos Esenciales/uso terapéutico , Neoplasias/química , Animales , Antineoplásicos/toxicidad , Ácidos Grasos Esenciales/toxicidad , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias Experimentales/química , Neoplasias Experimentales/tratamiento farmacológicoRESUMEN
Tumour cell drug resistance is a major problem in cancer chemotherapy. Essential fatty acids have been shown to be cytotoxic to a variety of tumour cells in vitro. But, the effect of these fatty acids on tumour cell drug resistance has not been well characterized. Gamma-linolenic acid (GLA) of the n-6 series and eicosapentaenoic acid (EPA) of the n-3 series potentiated the cytotoxicity of anti-cancer drugs: vincristine, cis-platinum and doxorubicin on human cervical carcinoma (HeLa) cells in vitro. Alpha-linolenic acid (ALA), GLA, EPA and docosahexaenoic acid (DHA) enhanced the uptake of vincristine by HeLa cells. In addition, DHA, EPA, GLA and DGLA were found to be cytotoxic to both vincristine-sensitive (KB-3-1) and -resistant (KB-ChR-8-5) human cervical carcinoma cells in vitro. Pre-incubation of vincristine-resistant cells with sub-optimal doses of fatty acids enhanced the cytotoxic action of vincristine. GLA, DGLA, AA, EPA and DHA enhanced the uptake and inhibited the efflux of vincristine and thus, augmented the intracellular concentration of the anti-cancer drug(s). Fatty acid analysis of KB-3-1 and KB-ChR-8-5 cells showed that the latter contained low amounts of ALA, GLA, 22:5 n-3 and DHA in comparison to the vincristine-sensitive cells. The concentrations of GLA and DHA were increased 10-15 fold in the phospholipid, free fatty acid and ether lipid cellular lipid pools of GLA and DHA treated cells. These results coupled with the observation that various fatty acids can alter the activity of cell membrane bound enzymes such as sodium-potassium-ATPase and 5'-nucleotidase, levels of various anti-oxidants, p53 expression and the concentrations of protein kinase C suggest that essential fatty acids and their metabolites can reverse tumour cell drug-resistance at least in vitro.
Asunto(s)
Resistencia a Medicamentos/fisiología , Ácidos Grasos Esenciales/farmacología , Neoplasias/metabolismo , 5'-Nucleotidasa/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Catalasa/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos/análisis , Ácidos Grasos Esenciales/metabolismo , Ácidos Grasos Esenciales/toxicidad , Ácidos Linolénicos/farmacología , Lípidos/análisis , Proteínas de la Membrana/metabolismo , Proteína Quinasa C/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Células Tumorales Cultivadas , Vincristina/farmacología , Vincristina/toxicidadRESUMEN
Polyunsaturated fatty acids (PUFA) have a selective cytotoxic/cytostatic effect on a number of tumor cell lines in culture. Although this process may be enhanced by the addition of iron there is a minimum level of PUFA necessary for potentiation of cell death. Vitamin E blocks PUFA cytotoxicity when added up to 5 days after fatty acid administration. Levels of thio-barbiturate reactive material (TBARM) in the medium rise in parallel with cell death. However, they are not affected by small alterations in temperature or oxygen tension. Incubating cells with PUFA causes marked alterations in the fatty acid patterns of both neutral and phospholipid fractions. Membrane fluidity is increased and the activity of membrane-bound receptors may be influenced directly or through the actions of eicosanoids derived from the exogenous fatty acid. PUFA may be an effective way of influencing tumor growth and a safe approach for the management of human cancer.
Asunto(s)
Antineoplásicos , Supervivencia Celular/efectos de los fármacos , Citotoxinas/toxicidad , Ácidos Grasos Esenciales/toxicidad , Peroxidación de Lípido/fisiología , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Humanos , Hierro/farmacología , Peroxidación de Lípido/efectos de los fármacos , Fluidez de la Membrana/efectos de los fármacos , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Células Tumorales Cultivadas , Vitamina E/farmacologíaRESUMEN
To compare the atherogenecity of different fats and oils, a total of forty, 40-day-old male Japanese quails were fed one of the following diets for three months: basal diet (control), a diet-containing 15% corn oil (CO) and 2% cholesterol (CH), a diet-containing 15% oleic acid (OL) and 2% CH, a diet-containing 15% perilla oil (PE) and 2% CH, a diet-containing 15% evening [corrected] primrose oil (PR) and 2% CH. A higher plasma cholesterol concentration was found in the birds in the CO and OL groups, whereas the PE and PR groups showed a much lower level of plasma cholesterol than the CO and OL groups. In proportion to the increased plasma cholesterol, both CO and OL groups showed narrowing of the lumen of the ascending aorta and its large branches due to marked lipid-rich intimal thickening. Ultrastructural changes in the ascending aorta and its large branches were correlated with the degree of intimal thickening. The major foam cell types were macrophages and fibroblastic cells. The PE and PR groups showed the fewest lipid-rich intimal thickening lesions in their ascending aorta and its large branches. These findings suggest that the alpha-linolenic acid contained in perilla oil is less atherogenic than oleic and linoleic acid, and gamma-linolenic acid contained in evening [corrected] primrose oil has a tendency to decrease the plasma lipid level.
Asunto(s)
Enfermedades de la Aorta/metabolismo , Arteriosclerosis/metabolismo , Grasas de la Dieta/toxicidad , Lípidos/análisis , Hígado/metabolismo , Aceites de Plantas/toxicidad , Animales , Aorta/química , Aorta/patología , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Arteriosclerosis/etiología , Arteriosclerosis/patología , Ésteres del Colesterol/sangre , Aceite de Maíz/toxicidad , Coturnix , Grasas de la Dieta/farmacocinética , Grasas Insaturadas en la Dieta/efectos adversos , Endotelio Vascular/ultraestructura , Ácidos Grasos Esenciales/toxicidad , Ácidos Linoleicos , Masculino , Microscopía Electrónica , Músculo Liso Vascular/ultraestructura , Oenothera biennis , Tamaño de los Órganos , Triglicéridos/sangre , Ácido alfa-Linolénico/toxicidad , Ácido gammalinolénicoRESUMEN
The paper summarizes the major morphological signs of nutritional lipid pathologies which have been reported in farmed fish, including nutritional pathologies arising from dietary essential fatty acid (EFA) deficiencies, nutritional pathologies resulting from dietary fatty acid toxicities and imbalances, and nutritional pathologies resulting from the dietary intake of oxidized lipids.
Asunto(s)
Carpas/fisiología , Enfermedades Carenciales/veterinaria , Enfermedades de los Peces/fisiopatología , Metabolismo de los Lípidos , Animales , Carpas/metabolismo , Enfermedades Carenciales/metabolismo , Enfermedades Carenciales/fisiopatología , Ácidos Grasos Esenciales/deficiencia , Ácidos Grasos Esenciales/toxicidad , Enfermedades de los Peces/metabolismo , Explotaciones Pesqueras , Italia , Peroxidación de Lípido , Lípidos/efectos adversosRESUMEN
The ingestion of high levels of fats, especially unsaturated fats, has been shown to enhance carcinogenesis in a variety of experimental model systems. Recently attention has focused upon the unsaturated linoleic fatty acid (18:2 omega 6) as a key component for this postinitiation enhancement. We have investigated the dose-effect relationship of this essential fatty acid (EFA), in a well-characterized experimental model of pancreatic cancer. Male Lewis rats were given injections i.p. of azaserine (30 mg/ kg) at 14 days of age. The pups were weaned to test diets that contained 20% total dietary fat with EFA compositions varying from 0.5 to 11.5% of the diet. After 4 months of feeding these 20% fat diets, the pancreases were evaluated in situ for grossly visible tumors and microscopically for the number and size of the azaserine-induced, putative preneoplastic lesions (foci). Grossly visible tumors increased significantly in number as the EFA content of the diet increased. Two populations of microscopic foci were observed in these azaserine-initiated rats; namely, acidophilic foci and basophilic foci. Quantitative stereological analyses of these foci revealed that the acidophilic population of foci increased in both number and size as the EFA content of the diet increased. This increase was particularly apparent from 4.4 to 8.5% dietary EFA content. The basophilic population showed no similar response to increasing dietary EFA. These results indicate that the minimum dietary EFA required for enhancement of azaserine-induced, pancreatic carcinogenesis by a high fat diet lies in the range of 4 to 8%.
Asunto(s)
Grasas de la Dieta/efectos adversos , Ácidos Grasos Esenciales/toxicidad , Neoplasias Pancreáticas/inducido químicamente , Animales , Azaserina/toxicidad , Basófilos/patología , Cocarcinogénesis , Relación Dosis-Respuesta a Droga , Masculino , Páncreas/patología , Neoplasias Pancreáticas/patología , Ratas , Ratas Endogámicas LewRESUMEN
In an attempt to determine the requirement of essential fatty acid for dimethylbenz(a)anthracene-induced mammary tumorigenesis, rats were fed diets containing different levels of linoleate: 0.5, 1.1, 1.7, 2.2, 3.5, 4.4, 8.5, or 11.5%. Each diet contained 20% of fat by weight, with varying amounts of coconut oil and corn oil added to achieve the desired levels of linoleate. Mammary tumorigenesis was very sensitive to linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary linoleate. Regression analysis indicated that a breakpoint occurred at 4.4%, beyond which there was a very poor linear relationship, suggesting the possibility of a plateau. From the intersection of the regression lines in both the upper and lower ranges, the level of linoleate required to elicit the maximal tumorigenic response was estimated to be around 4%. The differences in tumor yield could not be correlated with changes in prostaglandin E concentration in the mammary fat pads of normal animals maintained on similar diets, suggesting that linoleate may act by some other mechanism to stimulate mammary tumorigenesis.