RESUMEN
Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs) of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization
Asunto(s)
Humanos , Ácidos Grasos/fisiología , Sistema Inmunológico/fisiología , Leucocitos/fisiologíaRESUMEN
Human and animal immune functions present sex dimorphism that seems to be mainly regulated by sex hormones. In the present study, the activities of the antioxidant enzymes total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in intraperitoneal resident macrophages from adult male and female rats. In addition to comparing males and females, we also examined the regulation of these enzyme activities in macrophages by sex steroids. GSH-Px activity did not differ between male and female macrophages. However, both total SOD and CAT activities were markedly higher in females than in males (83 and 180 percent). Removal of the gonads in both males and females (comparison between castrated groups) increased the difference in SOD activity from 83 to 138 percent and reduced the difference in CAT activity from 180 to 86 percent. Castration and testosterone administration did not significantly modify the activities of the antioxidant enzymes in male macrophages. Ovariectomy did not affect SOD or GSH-Px activity but markedly reduced (48 percent) CAT activity. This latter change was fully reversed by estrogen administration, whereas progesterone had a smaller effect. These results led us to conclude that differences in the SOD and CAT activities may partially explain some of the differences in immune function reported for males and females. Also, estrogen is a potent regulator of CAT in macrophages and therefore this enzyme activity in macrophages may vary considerably during the menstrual cycle
Asunto(s)
Animales , Femenino , Ratas , Antioxidantes/metabolismo , Hormonas Esteroides Gonadales/farmacología , Peroxidación de Lípido/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Oxidorreductasas/metabolismo , Castración , Catalasa/metabolismo , Estrógenos/farmacología , Glutatión Peroxidasa/metabolismo , Macrófagos Peritoneales/enzimología , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Caracteres Sexuales , Superóxido Dismutasa/metabolismo , Testosterona/farmacologíaRESUMEN
The effect of free cholesterol on the fatty acid composition and growth of rat fetal enterocytes was investigated in the absence and presence of 10 percent (v/v) fetal calf serum. Cholesterol caused a significant reduction of cell number after 6 and 12 h in culture. The fatty acid composition of enterocytes cultured in the presence of serum was also changed by the presence of 20 æM cholesterol. The fatty acid profile was determined by HPLC using fluorescence detection (325 nm excitation and 395 nm emission). Cholesterol (20 æM) increased the proportion (given in percentage of the total fatty acids) of the following fatty acids in cultured cells: lauric (by 42 percent), oleic (by 34 percent), linoleic (by 44 percent) and gamma-linolenic (by 20 percent) acids and reduced the proportion of palmitic (by 12 percent), stearic (by 20 percent), arachidonic (by 21 percent) and docosahexaenoic (by 44 percent) acids. In addition to modifying the content of individual fatty acids, cholesterol increased the polyunsaturated/saturated fatty acid ratio from 0.48 to 0.67 and the unsaturation index from 67.12 to 75.30. This is the first evidence that cholesterol modifies fatty acid composition possibly via de novo fatty acid synthesis and desaturation
Asunto(s)
Animales , Masculino , Femenino , Embarazo , Ratas , Colesterol , Enterocitos , Ácidos Grasos , División Celular , Cromatografía Líquida de Alta Presión , Enterocitos , Ácidos Grasos , Ratas WistarRESUMEN
The aim of the present study was to investigate the effects of daily intragastric administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil), corresponding to 0.4 percent of body weight for four weeks, on fatty acid composition and oxidative stress (lipid peroxidation and catalase activity) in mouse liver. The activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), biomarkers of tissue injury, were determined in liver homogenates and serum. The proportions of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37 to 60 percent) in the total fatty acid content were increased in the liver of the bullfrog oil-treated group (P < 0.05) compared to control. At the same time, a significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated fatty acids, from 49 to 25 percent) was observed. The hepatic content of thiobarbituric acid reactive substances (TBARS) was increased from 2.3 ± 0.2 to 12.3 ± 0.3 nmol TBA-MDA/mg protein and catalase activity was increased from 840 ± 32 to 1110 ± 45 æmol reduced H2O2 min-1 mg protein-1 in the treated group. Bullfrog oil administration increased AST and ALP activities in the liver (from 234.10 ± 0.12 to 342.84 ± 0.13 and 9.38 ± 0.60 to 20.06 ± 0.27 U/g, respectively) and in serum (from 95.41 ± 6.13 to 120.32 ± 3.15 and 234.75 ± 11.5 to 254.41 ± 2.73 U/l, respectively), suggesting that this treatment induced tissue damage. ALT activity was increased from 287.28 ± 0.29 to 315.98 ± 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT activity was not affected by bullfrog oil treatment. Therefore, despite the interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use requires care since some adverse effects were observed in liver.