Eicosanoids and cancer

Eicosanoids are 20-carbon bioactive lipids derived from the metabolism of polyunsaturated fatty acids, which can modulate various biological processes including cell proliferation, adhesion and migration, angiogenesis, vascular permeability and inflammatory responses. In recent years, studies have shown the importance of eicosanoids in the control of physiological and pathological processes associated with several diseases, including cancer. The polyunsaturated fatty acid predominantly metabolized to generate 2-series eicosanoids is arachidonic acid, which is the major n-6 polyunsaturated fatty acid found in animal fat and in the occidental diet. The three main pathways responsible for metabolizing arachidonic acid and other polyunsaturated fatty acids to generate eicosanoids are the cyclooxygenase, lipoxygenase and P450 epoxygenase pathways. Inflammation plays a decisive role in various stages of tumor development including initiation, promotion, invasion and metastasis. This review will focus on studies that have investigated the role of prostanoids and lipoxygenase-derived eicosanoids in the development and progression of different tumors, highlighting the findings that may provide insights into how these eicosanoids can influence cell proliferation, cell migration and the inflammatory process. A better understanding of the complex role played by eicosanoids in both tumor cells and the tumor microenvironment may provide new markers for diagnostic and prognostic purposes and identify new therapeutic strategies in cancer treatment.

Effect of different commercial fat sources on brain, liver and blood lipid profiles of rats in growth phase

Abstract Purpose: To investigate the fatty acid content of different fat sources and evaluate the effect of them on plasma and hepatic lipids and on the fatty acid profile of the brain tissue of Wistar rats. Methods: Thirty male albino Wistar rats received for 59 days, the following diets: diet added of margarine with low content of polyunsaturated fatty acids (PUFA); diet added of margarine with high content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat; diet added of soybean oil. Fatty acid profile of the lipid sources, blood and hepatic lipids fractions and fatty acid profile of the brain tissue were determined. Results: Margarine consumption of provided different responses as to concentrations of blood and hepatic lipid fractions. Intake of butter and hydrogenated increased LDL-c/HDL-c ratio, being the steepest increase promoted by hydrogenated vegetable fat, which also raised LDL-c levels expressively. All fats used in the treatments reduced the cerebral concentration of docosahexaenoic acid when compared to soybean oil (control). Conclusion: The different fat sources commonly consumed by population provided different responses in vivo. This is particularly relevant considering the role of these lipids in the incidence and prevention of cardiovascular diseases.

Heart Rate Variability Correlates to Functional Aerobic Impairment in Hemodialysis Patients / Variabilidade RR ao Esforço Correlaciona-se com Déficit Funcional Aeróbico em Pacientes em Hemodiálise

Background: Autonomic dysfunction (AD) is highly prevalent in hemodialysis (HD) patients and has been implicated in their increased risk of cardiovascular mortality. Objective: To correlate heart rate variability (HRV) during exercise treadmill test (ETT) with the values obtained when measuring functional aerobic impairment (FAI) in HD patients and controls. Methods: Cross-sectional study involving HD patients and a control group. Clinical examination, blood sampling, transthoracic echocardiogram, 24-hour Holter, and ETT were performed. A symptom-limited ramp treadmill protocol with active recovery was employed. Heart rate variability was evaluated in time domain at exercise and recovery periods. Results: Forty-one HD patients and 41 controls concluded the study. HD patients had higher FAI and lower HRV than controls (p<0.001 for both). A correlation was found between exercise HRV (SDNN) and FAI in both groups. This association was independent of age, sex, smoking, body mass index, diabetes, and clonidine or beta-blocker use, but not of hemoglobin levels. Conclusion: No association was found between FAI and HRV on 24-hour Holter or at the recovery period of ETT. Of note, exercise HRV was inversely correlated with FAI in HD patients and controls. (Arq Bras Cardiol. 2015; [online]. ahead print, PP.0-0) .

Fundamento: A disfunção autonômica (DA) é altamente prevalente em pacientes em hemodiálise (HD) e tem sido implicada no risco aumentado de mortalidade cardiovascular. Objetivo: Correlacionar a variabilidade RR (VRR) durante o teste ergométrico (TE) com o déficit funcional aeróbico (FAI) em pacientes em HD e em um grupo controle. Métodos: Trata-se de um estudo transversal no qual as variáveis analisadas foram obtidas através de exame clínico, coleta de sangue, ecocardiograma transtorácico, Holter de 24 horas e TE. Foi realizado TE em esteira pelo protocolo de rampa, limitado por sintomas, com recuperação ativa. A VRR foi avaliada no domínio do tempo no exercício e na recuperação separadamente. Resultados: Quarenta e um pacientes em HD e 41 controles concluíram o estudo. Pacientes em HD tinham maior FAI e menor VRR do que os controles (p <0,001 para ambos). Houve correlação entre FAI e VRR no exercício (SDNN) em ambos os grupos. Esta associação foi independente de idade, sexo, tabagismo, índice de massa corporal, diabetes, clonidina, betabloqueador, mas não dos níveis de hemoglobina. Conclusão: A VRR no exercício foi inversamente correlacionada com o FAI em pacientes em HD e controles. Não foram observadas associações do FAI com VRR no Holter ou no período de recuperação do TE. .

Neurology at Escola Paulista de Medicina (1933-1995). From Fausto Guerner to José Geraldo Camargo Lima / Neurologia na Escola Paulista de Medicina (1933-1995). De Fausto Guerner a José Geraldo Camargo Lima.

Escola Paulista de Medicina (EPM) was founded in 1933 and the first Professor of Neurology was Fausto Guerner, who could not effectively assume the teaching activities due to his premature death in 1938. Professor Guerner had had his neurological training at Paris. Professor Longo was his successor. Longo was one of the founders of Arquivos de Neuro-Psiquiatria the foremost journal of neurosciences in Latin American. Longo died in 1967 and Professor Paulo Pupo succeeded him. Pupo introduced electroencephalography in Brazil. After his death in 1970, Professor Dante Giorgi succeeded him until 1974. Professor José Geraldo Camargo Lima took over the position after Giorgi’s death. He created the Neurological Emergency unit, initiated the Post-Graduation in Neurology and divided the Discipline in specialized units. During the 1980’s and until his retirement in 1995, EPM had become one of most important centers of Brazil training neurologists and researchers in neurological sciences.

A Escola Paulista de Medicina foi fundada em 1933 e o primeiro Professor de Neurologia foi Fausto Guerner, que morreu prematuramente em 1938, antes do início das aulas. O Professor Paulino Longo foi o seu sucessor. Longo, juntamente com outros, fundou os Arquivos de Neuro-Psiquiatria e a Academia Brasileira de Neurologia. Professor Paulo Pupo, seu sucessor, introduziu a eletroencefalografia no Brasil. O Professor José Geraldo Camargo Lima tornou-se chefe da Neurologia em 1974. Criou o Pronto-Socorro de Neurologia, iniciou a Pós-Graduação e dividiu a disciplina em setores especializadas. A partir dos anos 1980, a Neurologia da EPM tornou-se um dos centros acadêmicos mais importantes do Brasil.

New mathematical derivations for calculation of ATP yield due to the complete oxidation of different types of fatty acids.

During the complete oxidation of fatty acids, the electrons removed from fatty acids in different forms (FADH2 and NADH2) pass through the respiratory chain, driving the ATP synthesis. Generally, the ATP yield due to the complete oxidation of fatty acids is calculated by sum total the ATPs obtained due to the oxidation of FADH2 and NADH2 due to lack of any particular method. This calculation is simple for saturated even numbered fatty acids, but in the case of saturated and unsaturated odd numbered fatty acids the calculation of ATP yield is difficult and needs mathematical calculations due to some changes in their β-oxidation pathway when compared to the pathway of saturated even numbered fatty acids. These calculations are made simple by our derivations and following formulae where we require only number of carbon atoms and double bonds present in a fatty acid. Our method is superior and easier in comparison to long mathematical calculations that are in the practice.

Gene transfer of Chlorella vulgaris n-3 fatty acid desaturase optimizes the fatty acid composition of human breast cancer cells

Chlorella vulgaris has the gene of n-3 fatty acid desaturase (CvFad3), which can synthesize the precursor of n-3 polyunsaturated fatty acids (PUFAs) or convert n-6 to n-3 PUFAs. The objective of the present study was to examine whether the CvFad3 gene from C. vulgaris can be functionally and efficiently expressed in human breast cancer cells and whether its expression can exert a significant effect on cell fatty acid composition. We inserted the CvFad3 gene into the plasmid pEGFP-C3 to construct the eukaryotic expression vector pEGFP-C3-n-3 and to express the n-3 Fad gene in human breast cancer cells (MCF-7 cells). Transfection of MCF-7 cells with the recombinant vector resulted in a high expression of n-3 fatty acid desaturase. Lipid analysis indicated that the ratio of n-6/n-3 PUFAs was decreased from 6:1 in the control cells to about 1:1 in the cells expressing the n-3 fatty acid desaturase. Accordingly, the CvFad3 gene significantly decreased the ratio of n-6/n-3 PUFAs of the MCF-7 cell membrane. The expression of the CvFad3 gene can decrease cell proliferation and promote cell apoptosis. This study demonstrates that the CvFad3 gene can dramatically balance the ratio of n-6/n-3 PUFAs and may provide an effective approach to the modification of the fatty acid composition of mammalian cells, also providing a basis for potential applications of its transfer in experimental and clinical settings.

Ácidos graxos poli-insaturados n-3 e n-6: metabolismo em mamíferos e resposta imune / Omega-3 and omega-6 polyunsaturated fatty acids: metabolism in mammals and immune response

A experimentação animal apresenta uma grande importância para o desenvolvimento da ciência. O uso de camundongos em experimentos ocorre devido à semelhança destes animais com os seres humanos, fácil criação e manutenção e resposta experimental bastante rápida. Esses animais possuem as mesmas enzimas dessaturases e elongases que os humanos, por isso são usados em pesquisas envolvendo incorporação e síntese de ácidos graxos em tecidos. Os ácidos graxos da família ômega-3 e ômega-6 são de suma importância na dieta humana, pois estes não são sintetizados pela síntese de novo e são precursores dos ácidos graxos poli-insaturados de cadeia muito longa, como os ácidos eicosapentaenóico, docosahexaenóico e araquidônico. Estes desempenham funções importantes no organismo, como a síntese de eicosanóides que estão envolvidos diretamente no sistema imune e nas respostas inflamatórias. A razão entre o consumo de ácidos graxos n-6 e n-3 na dieta é um importante fator para determinar a ingestão adequada de ácidos graxos bem como prevenir o aparecimento de doenças. Este artigo tem como objetivo avaliar a incorporação de ácidos graxos em tecidos de animais e discutir a importância dos ácidos da família n-3 e seus metabólitos no sistema imunológico.

Experiments with animals are very important for the improvement of science. The use of mice in experiments is due to their similarity with humans, the easy of raising and maintaining them and their very fast response. These animals have the same desaturase and elongase enzymes as humans and so they are used in research involving the incorporation and synthesis of fatty acids in tissues. The fatty acids omega-3 and omega-6 are extremely important in the human diet because they are not synthesized de novo and are precursors of very long-chain polyunsaturated fatty acids, such as the eicosapentaenoic, docosahexaenoic and arachidonic acids. These acids play important roles in animals, such as precursors of eicosanoids, which are directly involved in the immune system and inflammatory response. The dietary n-3:n-6 intake ratio is important for assessing proper fatty acid intake and for preventing the development of diseases. Thus, this article assessed the incorporation of fatty acids in animal tissues and discussed the importance of n-3 fatty acids and its metabolites for the immune system.

Ácidos grasos con isomería trans I: su origen y los efectos en la salud humana / Isomeric trans fatty acids I: origin and effects in human health

It has been observed that foods with similar amount of starch can generate different glycemic responses. The evidence of a direct link between saturated fat consumption and an increased risk of cardiovascular diseases has led consumers to consider oils derived from vegetables, and industrial products derived from them, as healthier substitutes than animal fats. During the technological manipulation of vegetable oils, in order to transform them into more stable products it is applied the process of hydrogenation. The main side effect of this process is the formation of geometric and positional isomers of the unsaturated fatty acids, primary trans isomers of fatty acids (TFA). Dietary TFA consumption has a biological and industrial origin; the latter found in margarine, shortening, home and industrial cooking oil, bakery goods, and the wide range of' snack foods. Substantial TFA amounts come from the so called "invisible fats", the raw material used to manufacture more complex foods. The current wisdom is that TFA have an adverse effect on cardiovascular health, and its consumption poses a potential risk for increasing the incidence of heart disease.

La evidencia sobre una relación directa entre el consumo de grasas saturadas y el riesgo de enfermedad cardiovascular ha llevado a que los consumidores consideren a los aceites vegetales y a los productos industriales que derivan de ellos, como productos más saludables y sustitutos de las grasas animales. Durante el procesamiento tecnológico de los aceites vegetales, con la finalidad de transformarlos en productos más estables, se aplica el proceso de hidrogenación. El principal efecto lateral de este proceso es la formación de isómeros geométricos y posicionales de los ácidos grasos insaturados, principalmente de isómeros trans (AGT). Los AGT dietarios tienen origen biológico y tecnológico; estos últimos se encuentran en margarinas y mantecas, en aceites de uso doméstico e industrial, en productos de horneo, y en una gran variedad de alimentos del tipo bocadillos. Las grasas utilizadas para la manufactura industrial de alimentos (grasa "invisible") contienen elevadas cantidades de AGT. La visión actual es que los AGT tienen efectos adversos en la salud cardiovascular y que su consumo constituye un riesgo potencial de incrementarlas enfermedades cardíacas.

A importância dos ácidos graxos poliinsaturados de cadeia longa na gestação e lactação / The significance of long chain polyunsaturated fatty acids in pregnancy and lactation

Os ácidos graxos poliinsaturados de cadeia longa (AGPICL), ácido docosahexaenóico (DHA) e ácido araquidônico (AA) são componentes essenciais não só para o desenvolvimento neurológico quanto para a função visual da criança. O objetivo desta revisão foi buscar estudos recentes sobre a importância desses nutrientes no período gestacional e neonatal. A maior necessidade dos AGPICL ocorre durante a vida intra-uterina e nos primeiros meses de vida. A mãe é um fator determinante na oferta desses ácidos graxos para a criança. O leite materno contém todos os nutrientes necessários para o crescimento e desenvolvimento da criança. O bebê não tem capacidade de elongação e dessaturação dos ácidos graxos e dessa maneira as fórmulas infantis devem conter AGPICL pré-formados.

Long chain polyunsaturated fatty acids (LC-PUFAS), docosahexaenoic acid (DHA) and arachinodonic acid (AA) are essential components for both neurological development and visual function of the child. This review focused on recent studies concerning the value of these nutrients during gestational and neonatal periods. The need for (LC-PUFAS) is enhanced during intra-uterine and first months of life. The mother is the principal source of fatty acids to the child. Maternal milk contains all required nutrients for infant's growth and development. Babies do not have the ability to elong and desaturate fatty acids therefore; feeding formulas should contain preformed LC-PUFAS.

Ácidos graxos poliinsaturados ômega-3 e ômega-6: importância e ocorrência em alimentos / Omega-3 and omega-6 polyunsaturated fatty acids: importance and occurrence in foods

Os ácidos graxos poliinsaturados abrangem as famílias de ácidos graxos ômega-3 e ômega-6. Os ácidos graxos de cadeia muito longa, como os ácidos araquidônico e docosaexaenóico, desempenham importantes funções no desenvolvimento e funcionamento do cérebro e da retina. Esse grupo de ácidos graxos não pode ser obtido pela síntese de novo, mas pode ser sintetizado a partir dos ácidos linoléico e alfa-linolênico presentes na dieta. Neste artigo são considerados os principais fatores que podem inibir a atividade das enzimas dessaturases envolvidas na síntese dos ácidos graxos de cadeia muito longa. São apresentadas as recomendações da razão ômega-6/ômega-3 na dieta, propostas em diversos países, sendo verificada a convergência para o intervalo de 4 a 5:1. São relacionados alimentos que podem contribuir para aumentar a ingestão do ácido alfa-linolênico e dos ácidos graxos de cadeia muito longa. A essencialidade dos ácidos graxos de cadeia muito longa é muito dependente do metabolismo do indivíduo, sendo que a razão n-6/n-3 da dieta exerce grande influência nesse sentido.

Polyunsaturated fatty acids include the classes of fatty acids designated as omega-3 and omega-6. Very-long-chain polyunsaturated fatty acids as arachidonic and docosahexaenoic have important roles in the development and functioning of the brain and retina. This group of fatty acids cannot be synthesized by de novo pathway, but can be formed from linoleic and alpha-linolenic acid present in diet. In this article, the main factors that can inhibit desaturase enzymes activity involved in the synthesis of MLC-PUFAs are considered. Recommendations of omega-6/omega-3 ratio in diet proposed in several countries are presented, showing a coverage range from 4 to 5:1. Foods that are sources of alpha-linolenic acid and Very-long-chain are listed. The essentiality of Very-long-chain is very dependent of individual metabolism, and omega-6/omega-3 dietary ratio has a great influence in their health effects.

Effects of elicitor and copper sulfate on grindelic acid production in submerged cultures of Grindelia pulchella

Grindelia pulchella callus and cell suspension cultures were established from seedling leaves. When several phytoregulator supplementations were assayed in solid Murashige and Skoog medium containing 3 percent (w/v) of sucrose (MS medium), combinations of indole-3-butyric acid (IBA) and N6-benzylaminopurine (BA) resulted the most appropriate conditions to generate fast growing friable calli with detectable levels of grindelic acid. Moreover, the same basal media supplemented with 20.0 µM IBA/4.4 µM BA was found to be optimal for cell growth in submerged cultures (µmax = 0.26 days-1) while the addition of 20.0 µM IBA/18.0 µM BA resulted in a relative higher metabolite production (4.55 mg/gDW) when the inocula was 5 percent (v/v). Furthermore, three different stress factors and combinations of them were used to elicit cell suspensions. These experiments demonstrated that the combination of CuSO4 and dimethylsulfoxide (DMSO) increase the grindelic acid production to 2.63 mg/gDW in the elicited essay versus 0.756 mg/gDW in the control, at expense of cell growth. In contrast, the addition of jasmonic acid (JA) alone and combined with DMSO neither affected cell growth nor grindelic acid accumulation.

Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology.

Numerous factors influence male fertility. Among these factors is oxidative stress (OS), which has elicited an enormous interest in researchers in recent period. Reactive oxygen species (ROS) are continuously produced by various metabolic and physiologic processes. OS occurs when the delicate balance between the production of ROS and the inherent antioxidant capacity of the organism is distorted. Spermatozoa are particularly sensitive to ROS as their plasma membrane contains polyunsaturated fatty acids (PUFA), which oxidizes easily. They also lack cytoplasm to generate a robust preventive and repair mechanism against ROS. The transition metal ions that are found in the body have a catalytic effect in the generation of ROS. Lifestyle behaviours such as smoking and alcohol use and environmental pollution further enhance the generation of ROS and thus, cause destructive effects on various cellular organelles like mitochondria, sperm DNA etc. This article analyzes the detrimental effects of OS on male fertility, measurement of OS and effective ways to decrease or eliminate them completely. We have also provided information on oxidative stress in other systems of the body, which may be applied to future research in the field of reproductive biology.

Angiotensin-II behaves as an endogenous pro-inflammatory molecule.

Angiotensin-II regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NF-kappaB, increases oxidant stress, and suppresses nitric oxide synthesis, and thus, it functions as an inflammatory molecule. Since ACE is present in many tissues, this suggests that angiotensin-II may play a significant role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is an aetiopathogenic factor. Thus, ACE inhibitors and/or angiotensin-II receptor blockers could be of benefit in these conditions. Furthermore, structural analogues of ACE inhibitors and angiotensin-II receptor blockers could be developed that possess anti-inflammatory actions without significant action on the cardiovascular system.

In vitro effects of organophosphate pesticides on rat erythrocytes.

In vitro effects of various organophosphate pesticides (dimethoate, chlorpyrifos, ethion and monocrotophos) were studied on hemolysis, K+ leakage and lipid peroxidation in rat erythrocytes. All the four pesticides increased hemolysis and K+ leakage from erythrocytes, that was concentration and time dependent. On the contrary, there was decrease in lipid peroxidation in erythrocyte membrane. Effect of pesticides on lipid peroxidation could be due to pesticide itself abstracting protons or interacting with free radicals rather than polyunsaturated fatty acids (PUFA), thereby protecting the latter against peroxidation.

Relación entre la ingesta de ácidos grasos, la oxidación de substratos energéticos y la respuesta insulínica / Dietary fatty acids and its relationship with energy substrates oxidation and insulin response

La presente revisión analiza los roles de los ácidos grasos dietarios; en primer lugar a nivel celular en lo que respecta a la diferenciación adipocítica, expresión génica de enzimas y la síntesis de proteínas involucradas en el metabolismo energético. En segundo lugar, se analiza los efectos de los ácidos grasos en el mejoramiento de la sensibilidad o de la resistencia insulínica, en particular sobre la relevancia de los ácidos grasos saturados versus los poliinsaturados. Finalmente, se describen los efectos de las distintas calidades de ácidos grasos sobre el metabolismo oxidativo de sustratos energéticos. En la actualidad se conoce que la mayoría de estos efectos pueden ser modulados a través de modificaciones dietéticas simples como por ejemplo la variación en el tipo de aceite ingerido. La relevancia de estos procesos en relación a la obesidad y sus alteraciones metabólicas se enfatizan de manera específica.

Modulação da composição de ácidos graxos polinsaturados ômega 3 de ovos e tecidos de galinhas poedeiras, através da dieta. I. Estabilidade oxidativa / Modulation of composition of the polyunsaturated fatty acids omega 3 in eggs and tissues of chicken laying, by diets. I. Oxidative stability

O objetivo deste estudo foi avaliar a influência de dietas suplementadas com semente de linhaça (ricas em ácido (ALFA)-linolênico, LNA, ômega 3) e antioxidantes naturais, provenientes do orégano e do alecrim, sobre o nível de incorporação dos ácidos graxos polinsaturados ômega 3 (PUFA ômega 3) em ovos e tecidos de aves. Para isto, 192 galinhas poedeiras da linhagem comercial Babcock de 22 semanas, foram alimentadas durante 30 dias com dietas constituídas de 0 (zero) e 5 por cento de óleo de linhaça. Foram definidos 8 tratamentos: 4 grupos com 5 por cento de óleo linhaça (controle/sem antioxidante; BHA+BHT, 100+100 ppm; orégano, 200ppm; alecrim, 200ppm) e 4 grupos sem óleo de linhaça, mas utilizando os mesmos antioxidantes...

Efeito antioxidante dos compostos fenólicos de especiarias sobre os ácidos graxos das séries OMEGA 3 E OMEGA 6 / Antioxidant effect of phenolic compounds of spices on the OMEGA 3 and OMEGA 6

Dentro da perspectiva da utilização de compostos fenólicos como antioxidantes naturais para minimizar os efeitos in vitro e in vivo do processo oxidativo dos lípides insaturados, foi realizada a monitoração dietética de duas dietas ricas em lípides das séries "OMEGA"3 e "OMEGA"6 e a suplementação de um chá de uma mistura de especiarias, em ratos Wistar, com o objetivo de verificar a influência dos compostos fenólicos, presentes nas especiarias, sobre o metabolismo de ácidos graxos das séries "OMEGA"3 e "OMEGA"6. Extratos e frações das especiarias mostarda, canela e erva doce foram obtidos e tiveram suas atividades antioxidantes testadas em sitemas aquoso (co-oxidação de sustratos com o uso de ácido linoléico/"BETA"-caroteno)...

Effect of methyl-prednisone and cyclosporine on the lipid pattern and polyunsaturated fatty acid biosynthesis in the rat

The hyperlipidemia posttransplant has been largely attributed to immunosuppressant agents. In the present work we evaluated the effect of oral administration of cyclosporine (5 mg/kg/day) and/or methyl1-prednisone (1 mg/kg/day) on lipid composition and polyunsaturated fatty acid biosynthesis in normal adult male rats. The results obtained showed that both agents produced a delay on the growth together with a significant loss of body weight. In liver microssomal fraction from rats treated with methyl1-prednisone, a depression in delta 6 and delta 5 desaturation activited, was observed. This effect was corroborated in the fatty acid pattern through the enhancement of linoleic and dihomo-gamma-linolenic acids, and a depression of arachidonic acid. Similar results were noticed in those rats treated with both drugs when compared to the controls. No changes were observed either in the amount of liver microsomal total lipids or in the fatty acid composition of kidney and testis microsomes, as well as in erythrocyte membranes, among the different groups studied. Cyclosporine alone produced a significant depression in plasma triglycerides and showed no modifications in the other lipid parameters studied compared to the controls. Fluorescence anisotropy measured in the different membranes was not modified by the several treatments used. In view of the aforementioned data, in can be stated that methyl-prednisone would be the responsible for many of the lipid disorders that can be observed in posttransplant patients when they are subjected to the combined immunotherapy with cyclosporine.

Dietary polyunsaturated fatty acids, and tissue oxidative stress: the effect of d,l-Ó-tocopherol

The effects of feeding young and aged rats with high doses of polyunsaturated fatty acids from marine oil on the susceptibility of erythrocyte membranes to the induction of oxidative stress, on the level of reduced glutathione of different tissues, and on the antioxidant capacity of blood plasma were studied. The protective effect of the supplementation of the oil with d,l-alpha-tocopherol was also assayed. d,l-alpha-Tocopherol supplementation protects erythrocyte membranes from young rats against the induction of oxidative stress, being unable to protect the membranes from the aged ones. The tripeptide glutathione shows a different behavior depending on the tissue. Blood glutathione is not affected by fish oil ingestion and by the d,l- alpha-tocopherol supplementation either in the young or in the aged animals. Liver glutathione is reduced by fish oil feeding in the aged animals only. Brain glutathione is not affected by the fish oil feeding. The supplementation with d,l-alpha-tocopherol restores the hepatic levels of glutathione and increases the brain level of the tripeptide over the controls, this effect being observed for young and the aged rats. The antioxidant capacity of blood plasma in response to the fish oil feeding increases in the young rats only. This capacity is not affected by the suplementation with d,l-alpha-tocopherol. These metabolic changes are ascribed to possible adaptative responses from the animals to the potential risk of oxidative stress induced by fish oil ingestion. We suggest that metabolic risks may be associated with the consumption of high doses of polyunsaturated fatty acids.