Interferential Current Electrotherapy is More Effective Thanthan TENS VIF in Cancer Pain Management / Corrente Interferencial é Mais Efetiva para Alívio da Dor Oncológica que a TENS VIF

Cancer diagnosis is increasing rapidly worldwide and pain is a common feature reported by cancer patients. Therapeutical approach on cancer pain is complex where less invasive methods with little side effects have been sought. The aim of this study was to compare transcutaneous electrical nerve stimulation (TENS) and interferential current (IC) therapies effects on cancer pain. Double blind study with 81 cancer pain patients. Subjects were set up into two groups: one treated with TENS VIF (n=42) and other with IC (n=39). Age, gender, duration of pain, tumor site and histology, medications, treatments, Karnofsky score and clinical state were evaluated. Pain was measured by EMADOR and McGill scores. Electroanalgesia was performed for 30 minutes, the equipments used were Neurodyn III Ibramed® and Neurovector generation 2000 Ibramed®. Electrodes were placed where there was higher intensity of pain according to what was shown by the patient through EMADOR, and each one got only one electrotherapy session. Pain intensity was significantly reduced in both groups (p<0.001) soon after and until 6th hour post electrotherapy. IC group had better results at 4th, 5th (p<0.001) and 6th hour (p=0.022). McGill score in TENS VIF group was significant until 4th hour and in the IC group was highly significant in all evaluated times (p<0.001). Analgesic effect of TENS VIF and IC electrotherapy was clinically effective, however, IC did cause better results regarding analgesia duration.(AU)

O diagnóstico de câncer está aumentando rapidamente em todo o mundo e a dor é uma característica comum relatada por pacientes com câncer. A abordagem terapêutica da dor oncológica é complexa onde métodos menos invasivos e com poucos efeitos colaterais têm sido buscados. O objetivo deste estudo foi comparar os efeitos das terapias de estimulação elétrica nervosa transcutânea (TENS) e corrente interferencial (IC) na dor oncológica. Estudo duplo-cego com 81 pacientes com dor oncológica. Os indivíduos foram divididos em dois grupos: um tratado com TENS VIF (n=42) e outro com IC (n=39). Idade, sexo, duração da dor, local do tumor e histologia, medicamentos, tratamentos, pontuação de Karnofsky e estado clínico foram avaliados. A dor foi mensurada pelos escores EMADOR e McGill. A eletroanalgesia foi realizada por 30 minutos, os equipamentos utilizados foram Neurodyn III Ibramed® e Neurovector geração 2000 Ibramed®. Os eletrodos foram colocados onde havia maior intensidade de dor de acordo com o apresentado pelo paciente através da EMADOR. A intensidade da dor foi significativamente reduzida em ambos os grupos (p<0,001) logo após e até a 6ª hora pós-eletroterapia. O grupo CI teve melhores resultados na 4ª, 5ª (p<0,001) e 6ª hora (p=0,022). O escore de McGill no grupo TENS VIF foi significativo até a 4ª hora e no grupo IC foi altamente significativo em todos os tempos avaliados (p<0,001). O efeito analgésico da TENS VIF e da eletroterapia com IC foi clinicamente eficaz, porém a IC trouxe melhores resultados quanto à duração da analgesia.(AU)

Biomarkers of oxidative stress and inflammation in people witha physical disability treated with a standardized extract of Nasturtium officinale: A randomized, double-blind, and placebo-controlled trial.

It is well established that plants from the Brassicaceae family, particularly watercress, have been associated to reduce oxidative DNA damage. Nasturtium officinale R. Br (watercress) contains glucosinolates, with anti-inflammatory action and protective effect on human health against oxidative stress. We aimed to evaluate whether the standardized extract of Nasturtium officinale (SENO) is capable of changing biomarkers of oxidative stress and inflammation in people with physical disabilities. 65 people enrolled this study: as a control group composed by; 15 people with no physical disability assessed once, 25 people with physical disabilities using 750 mg/kg/day of SENO, and 25 people with physical disabilities using 750 mg/kg/day of placebo-control for 5 weeks. Biomarkers of oxidative stress and inflammation were analyzed on day 0 and 36. The results indicated that SENO was associated with decreasing levels of lipid peroxidation, protein carbonyl, catalase, superoxide dismutase, and C-reactive protein. Furthermore, the cytokine kit demonstrated below and out of invertible range, which was impossible to detect the inflammatory process. Despite the cytokine kit was not able to detect the inflammation; these data might provide supportive evidence that SENO, have affected positively people with physical disabilities decreasing their biomarkers of oxidative stress and C-reactive protein. Further studies are required.

Consumption of latex from Euphorbia tirucalli L. promotes a reduction of tumor growth and cachexia, and immunomodulation in Walker 256 tumor-bearing rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L. is an African plant that grows well in Brazil. Individuals diagnosed with cancer frequently consume latex from E. tirucalli, dissolved in drinking water. In vitro studies confirm the antitumor potential of E. tirucalli latex, but in vivo evaluations are scarce. AIM OF THE STUDY: To evaluate the effect of intake of an aqueous solution of E. tirucalli latex on tumor growth, cachexia, and immune response in Walker 256 tumor-bearing rats. MATERIALS AND METHODS: Latex from E. tirucalli was collected and analyzed by LC-MS. Sixty male Wistar rats (age, 90 days) were randomly divided into four groups: C, control group (without tumor); W, Walker 256 tumor-bearing group; SW1, W animals but treated with 25 µL latex/mL water; and SW2, W animals but treated with 50 µL latex/mL water. Animals received 1 mL of latex solution once a day by gavage. After 15 d, animals were euthanized, tumor mass was determined, and glucose and triacylglycerol serum levels were measured by using commercial kits. Change in the body weight during tumor development was calculated, and proliferation capacity of tumor cells was assessed by the Alamar Blue assay. Phagocytosis and superoxide anion production by peritoneal macrophages and circulating neutrophils were analyzed by enzymatic and colorimetric assays. Data are analyzed by one-way ANOVA followed by Tukey's post-hoc test, with the significance level set at 5%. RESULTS: The analysis of the latex revealed the presence of triterpenes. The ingestion of the latex aqueous solution promoted 40% and 60% reduction of the tumor mass in SW1 and SW2 groups, respectively (p < 0.05). The proliferative capacity of tumor cells from SW2 group was 76% lower than that of cells from W group (p < 0.0001). Animals treated with latex gained, on average, 20 g (SW1) and 8 g (SW2) weight. Glucose and triacylglycerol serum levels in SW1 and SW2 animals were similar to those in C group rats. Peritoneal macrophages and blood neutrophils from SW1 and SW2 animals produced 30-40% less superoxide anions than those from W group animals (p < 0.05), but neutrophils from SW2 group showed an increased phagocytic capacity (20%, vs. W group). CONCLUSIONS: E. tirucalli latex, administered orally for 15 d, efficiently reduced tumor growth and cachexia in Walker 256 tumor-bearing rats. Decreased tumor cell proliferative capacity was one of the mechanisms involved in this effect. Further, the data suggest immunomodulatory properties of E. tirucalli latex. The results agree with folk data on the antitumor effect of latex ingestion, indicating that it may be useful as an adjunct in the treatment of cancer patients. For this, further in vivo studies in animal and human models need to be conducted.

New insights on the regulation of cancer cachexia by N-3 polyunsaturated fatty acids.

Cancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in an intense catabolic state, decreased activity of anabolic pathways, anorexia, and marked weight loss, leading to cachexia development and/or accentuation. Inflammatory mediators appear to be related to the control of a highly regulated process of muscle protein degradation that accelerates the process of cachexia. Several mediators have been postulated to participate in this process, including TNF-α, myostatin, and activated protein degradation pathways. Some interventional therapies have been proposed, including nutritional (dietary, omega-3 fatty acid supplementation), hormonal (insulin), pharmacological (clenbuterol), and nonpharmacological (physical exercise) therapies. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid, are recognized for their anti-inflammatory properties and have been used in therapeutic approaches to treat or attenuate cancer cachexia. In this review, we discuss recent findings on cellular and molecular mechanisms involved in inflammation in the cancer cachexia syndrome and the effectiveness of n-3 PUFAs to attenuate or prevent cancer cachexia.

Immunomodulatory and Antitumoral Properties of Ganoderma lucidum and Agaricus brasiliensis (Agaricomycetes) Medicinal Mushrooms.

Medicinal mushrooms are used in popular medicine largely as health promoters, mainly because of their antitumor and immunomodulatory activities. Ganoderma lucidum (lingzhi or reishi) and Agaricus brasiliensis are mushrooms that have long been used for medicinal purposes. This study evaluated their immunomodulatory and antitumor effects on mice fed a diet supplemented with G. lucidum and A. brasiliensis mycelia obtained from solid-state fermentation. For 14 weeks the mice were fed chow containing 50% A. brasiliensis and G. lucidum mycelia, using ground wheat as an excipient. The consumption of the supplemented diet inhibited Sarcoma 180 tumor growth and caused important changes in the immune system. The pattern of immune response shifted, increasing CD4+ and CD8+ and decreasing CD19+ cell populations. The restoration of a proper balance between cellular and humoral immunity is an essential process for restraining tumor growth. These results suggest that polysaccharides, such as ß-glucans and other mushroom metabolites, possibly promote the T-cell dominance that is imperative to restrain tumor growth.

Fish Oil Supplementation Enhances Pulmonary Strength and Endurance in Women Undergoing Chemotherapy.

We investigated the effect of fish oil (FO) supplementation, at 4 g/day, on the respiratory performance and blood lipid profile of 32 patients with breast cancer at the beginning of chemotherapy. They were randomized into two groups: control (C) and FO supplemented (S). Both groups underwent three respiratory evaluations and blood harvest (before chemotherapy-Day 0, and 30 and 60 days after supplementation). The S group showed a significant increase in the maximal inspiratory and expiratory pressure (P ≤ 0.05 vs. Day 0) and in the maximum voluntary ventilation (P ≤ 0.05). In the treadmill 6-min-walk test, the S group had a significant increase in the walked distance (P ≤ 0.05). Blood lactate concentration was significantly lower in the S group after 60 days, at rest, when compared to C (P ≤ 0.05). Plasma high-density lipoprotein (HDL) cholesterol concentration remained the same after 60 days of supplementation, while in the C group, it decreased significantly (P ≤ 0.05 Day 0 vs. Day 60). Triacylglycerol (TAG) plasma concentration in the S group was lower when compared to the C group (P ≤ 0.05 Day 60S vs. Day 60). Supplementation with FO caused improvement in the respiratory muscle strength and endurance, ameliorated functional performance, and kept TAG, HDL cholesterol, and lactate plasma concentration at normal levels.

Fish oil administration mediates apoptosis of Walker 256 tumor cells by modulation of p53, Bcl-2, caspase-7 and caspase-3 protein expression.

BACKGROUND: Several studies have been shown pro-apoptotic effects of fish oil (FO), rich in n-3 polyunsaturated fatty acids (n-3 PUFA) on cancer cells. Nevertheless, few in vivo experiments have provided data of its ability on apoptosis protein expression in tumor tissue. Thus, in this study we investigate the effect of FO supplementation on apoptosis protein expression in Walker 256 tumor bearing rats. Male Wistar rats were randomly assigned to three groups: fed with regular chow (W); fed regular chow supplemented with FO (WFO) or coconut fat (WCO) (1 g/kg body weight/daily). After thirty days, all animals were inoculated subcutaneously with Walker 256 tumor cells. FINDINGS: Protein expression was done by western blotting in Walker 256 tumor tissue samples. FO decreased the Bcl-2/Bax ratio (p < 0.05) and increased the p53 (p < 0.05), cleaved caspase-7 (p < 0.05) and cleaved caspase-3 (p < 0.05) in Walker 256 tumor tissue. CONCLUSIONS: Our data suggest that the pro-apoptotic effect of FO in Walker 256 tumor is related with specifics cleaved caspases.

Influence of fish oil supplementation and strength training on some functional aspects of immune cells in healthy elderly women.

Immune function changes with ageing and is influenced by physical activity (strength training, ST) and diet (fish oil, FO). The present study investigated the effect of FO and ST on the immune system of elderly women. Forty-five women (64 (sd 1.4) years) were assigned to ST for 90 d (ST; n 15), ST plus 2 g/d FO for 90 d (ST90; n 15) or 2 g/d FO for 60 d followed by ST plus FO for 90 d (ST150; n 15). Training was performed three times per week, for 12 weeks. A number of innate (zymosan phagocytosis, lysosomal volume, superoxide anion, peroxide of hydrogen) and adaptive (cluster of differentiation 4 (CD4), CD8, TNF-α, interferon-γ (IFN-γ), IL-2, IL-6 and IL-10 produced by lymphocytes) immune parameters were assessed before supplementation (base), before (pre-) and after (post-) training. ST induced no immune changes. FO supplementation caused increased phagocytosis (48 %), lysosomal volume (100 %) and the production of superoxide anion (32 %) and H2O2(70 %) in the ST90. Additional FO supplementation (ST150) caused no additive influence on the immune system, as ST150 and ST90 did not differ, but caused greater changes when compared to the ST (P< 0·05). FO increased CD4+ and CD8+ lymphocytes in the ST150, which remained unchanged when training was introduced. The combination of ST and FO reduced TNF-α in the ST150 from base to post-test. FO supplementation (ST150, base-pre) when combined with exercise (ST150, pre-post) increased IFN-γ, IL-2, IL-6 and IL-10 production. The immune parameters improved in response to FO supplementation; however, ST alone did not enhance the immune system.

Antitumor and anti-cachectic effects of shark liver oil and fish oil: comparison between independent or associative chronic supplementation in Walker 256 tumor-bearing rats.

BACKGROUND: Shark liver oil (SLOil) and fish oil (FOil), which are respectively rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are able to reduce the growth of some tumors and the burden of cachexia. It is known that FOil is able to reduce proliferation rate and increase apoptotic cells and lipid peroxidation of tumor cells efficiently. However, there are few reports revealing the influence of SLOil on these parameters. In the current study, effects of FOil chronic supplementation on tumor growth and cachexia were taken as reference to compare the results obtained with SLOil supplementation. Also, we evaluated if the association of SLOil and FOil was able to promote additive effects. METHODS: Weanling male Wistar rats were divided into 4 groups: fed regular chow (C), supplemented (1 g/kg body weight) with SLOil (CSLO), FOil (CFO) and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker 256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG composition of tumor and oils were obtained by high performance liquid chromatography and gas chromatography - mass spectrometry, respectively. Statistical analysis was performed by unpaired t-test and one-way ANOVA followed by a post hoc Tukey test. RESULTS: Fourteen days after inoculation, SLOil was able to restore cachexia parameters to control levels, similarly to FOil. WSLO rats presented significantly lower tumor weight (40%), greater tumor cell apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed more potent effects. Supplementation with SLOil + FOil did not promote additive effects. Additionally, chromatographic results suggested a potential incorporation competition between the n-3 fatty acids and the AKGs in the tumor cells' membranes. CONCLUSIONS: SLOil is another marine source of lipids with similar FOil anti-cachectic capacity. Furthermore, despite being less potent than FOil, SLOil presented significant in vivo antitumor effects. These results suggest that the chronic supplementation with SLOil may be adjuvant of the anti-cancer therapy.

Relationship between acute phase proteins and serum fatty acid composition in morbidly obese patients.

BACKGROUND: Obesity is considered a low-grade inflammatory state and has been associated with increased acute phase proteins as well as changes in serum fatty acids. Few studies have assessed associations between acute phase proteins and serum fatty acids in morbidly obese patients. OBJECTIVE: To investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid, and Albumin) and serum fatty acids in morbidly obese patients. METHODS: Twenty-two morbidly obese patients were enrolled in this study. Biochemical and clinical data were obtained before bariatric surgery, and fatty acids measured in preoperative serum. RESULTS: Orosomucoid was negatively correlated with lauric acid (P = 0.027) and eicosapentaenoic acid (EPA) (P = 0.037) and positively with arachidonic acid (AA) (P = 0.035), AA/EPA ratio (P = 0.005), and n-6/n-3 polyunsaturated fatty acids ratio (P = 0.035). C-Reactive Protein (CRP) was negatively correlated with lauric acid (P = 0.048), and both CRP and CRP/Albumin ratio were negatively correlated with margaric acid (P = 0.010, P = 0.008, resp.). Albumin was positively correlated with EPA (P = 0.027) and margaric acid (P = 0.008). Other correlations were not statistically significant. CONCLUSION: Our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients.

Fish oil supplementation reduces cachexia and tumor growth while improving renal function in tumor-bearing rats.

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FE(Na+)) of FO rats was similar to C. Proximal Na(+) reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B(2) (TXB(2)) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats.

We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

BACKGROUND: Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. METHODS: Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. RESULTS: Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. CONCLUSIONS: Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Medicinal mushroom Ganoderma lucidum (Leyss: Fr) Karst. triggers immunomodulatory effects and reduces nitric oxide synthesis in mice.

This study investigated the effect of Ganoderma lucidum supplementation on lymphocytes and peritoneal macrophages from mice. Our results show that G. lucidum in vivo was able to increase interferon-gamma (IFN-gamma) concentration but reduced CD3(+) and CD8(+) spleen lymphocytes. Ex vivo, IFN-gamma; and interleukin-10 levels were increased and the tumor necrosis factor-alpha (TNF-alpha) level was reduced by peritoneal macrophages from mice fed with G. lucidum. In the absence of stimuli nitric oxide production was reduced in mice fed with G. lucidum, and with lipopolysaccharide stimulation nitric oxide production was increased but was lower than control values (P < .05). G. lucidum was grown by solid-state culture in wheat grain, and a chow containing 10% G. lucidum mycelium was formulated (G10). Swiss male mice were divided into two groups, termed G10 and control groups according to the diet, and were fed for 3 months. Peritoneal macrophages were obtained and investigated with regard to phagocytosis, lysosomal volume, hydrogen peroxide, superoxide anion, and cytokines ex vivo. In the plasma we investigated concentrations of cytokines, and in the spleen we determined subsets of CD3(+), CD4(+), CD8(+), and CD19(+) lymphocytes.

Effect of chronic supplementation with shark liver oil on immune responses of exercise-trained rats.

Previous studies have reported that chronic supplementation with shark liver oil (SLO) improves immune response of lymphocyte, macrophage and neutrophil in animal models and humans. In a similar manner, exercise training also stimulates the immune system. However, we are not aware of any study about the association of exercise and SLO supplementation on immune response. Thus, our main goal was to investigate the effect of chronic supplementation with SLO on immune responses of exercise-trained rats. Male Wistar rats were divided into four groups: sedentary with no supplementation (SED, n = 20), sedentary with SLO supplementation (SEDslo, n = 20), exercised (EX, n = 17) and exercised supplemented with SLO (EXslo, n = 19). Rats swam for 6 weeks, 1.5 h/day, in water at 32 +/- 1 degrees C, with a load of 6.0% body weight attached to the thorax of rat. Animals were killed 48 h after the last exercise session. SLO supplementation did not change phagocytosis, lysosomal volume, superoxide anion and hydrogen peroxide production by peritoneal macrophages and blood neutrophils. Thymus and spleen lymphocyte proliferation were significantly higher in SEDslo, EX, and EXslo groups compared with SED group (P < 0.05). Gut-associated lymphocyte proliferation, on the other hand, was similar between the four experimental groups. Our findings show that SLO and EX indeed are able to increase lymphocyte proliferation, but their association did not induce further stimulation in the adaptive immune response and also did not modify innate immunity.

Atualizações sobre beta-hidroxi-beta-metilbutirato: suplementação e efeitos sobre o catabolismo de proteínas / New findings on beta-hydroxy-beta-methylbutyirate: supplementation and effects on the protein catabolism

O beta-hidroxi-beta-metilbutirato, metabólito do aminoácido leucina, vem sendo utilizado como suplemento alimentar, em situações específicas, com o intuito de aumentar ou manter a massa isenta de gordura. Os relatos dos efeitos do beta-hidroxi-beta-metilbutirato em estudos recentes fizeram crescer as expectativas sobre sua utilização em casos patológicos. Também foram demonstrados melhores resultados, quando da sua ingestão, no treinamento de força em indivíduos iniciantes e em idosos. Em humanos o beta-hidroxi-beta-metilbutirato tem sido usado como agente anti-catabólico, e em modelos animais foi demonstrado ser eficaz em inibir a atividade de vias proteolíticas em células musculares de indivíduos caquéticos in vitro e in vivo. Os mecanismos participantes desses processos envolvem: a inibição da atividade do sistema ubiquitina proteossoma ATP-dependente, a inibição de vias de sinalização com participação da proteína quinase C-alfa e a diminuição da concentração citoplasmática do fator nuclear - kappa B livre, eventos relacionados ao decréscimo da proteólise em células musculares.

The leucine metabolite beta-hydroxy-beta-methylbutyrate has been used as a nutritional supplement in specific situations to prevent losing or to increase lean mass. Recent studies showed interesting results of beta-hydroxy-beta-methylbutyrate supplementation in certain disease states. Better results have also been demonstrated when it is taken by starters or old individuals doing strength training. In humans, beta-hydroxy-beta-methylbutyrate has been used as an anticatabolic agent and in animal models it has been demonstrated to be effective in inhibiting the activity of the proteolytic pathways in muscle cells of extremely weak individuals in vivo and in vitro. The mechanisms that participate in this process involve: inhibition of the ATP-ubiquitin-proteasome pathway, inhibition of the signalization pathways involving protein kinase C-alpha and reduction of the cytoplasmatic concentration of free nuclear factor kappa-B, events that are associated with the reduction of proteolysis in muscle cells.

Fish oil alters T-lymphocyte proliferation and macrophage responses in Walker 256 tumor-bearing rats.

OBJECTIVE: We investigated the effect of the dietary ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) from postweaning until adulthood on T-lymphocyte proliferation, T-lymphocyte subpopulations (helper and cytotoxic), and production of cytotoxic mediators by macrophages in tumor-bearing rodents. METHODS: Weanling male Wistar rats received a normal low-fat (40 g/kg of diet) chow diet or a high-fat (300 g /kg) diet that included fish or sunflower oil or blends of fish and sunflower oils to yield omega-6:omega-3 PUFA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, 50% of rats in each group were inoculated with 1 mL of 2 x 10(7) Walker 256 cells. Fourteen days after tumor inoculation, animals were killed and lymphocytes and macrophages were obtained for study. RESULTS: The diets richest in omega-6 PUFA resulted in higher proliferation of thymus, spleen, and gut-associated lymphocytes compared with the chow diet irrespective of tumor burden. In contrast, the fish oil diet resulted in lower proliferation of thymus and spleen lymphocytes compared with the chow diet. Diets rich in omega-6 PUFA decreased the proportion of CD8+ lymphocytes. In non-tumor-bearing and tumor-bearing rats, hydrogen peroxide production by macrophages was highest in rats that consumed diets high in omega-3 PUFAs. Superoxide and nitric oxide production were little affected by the dietary ratio of omega-6 to omega-3 PUFAs. CONCLUSION: Dietary omega-6 and omega-3 PUFA contents alter immune function in non-tumor-bearing and tumor-bearing rats. The omega-3 PUFAs decreased T-cell proliferation but increased hydrogen peroxide production compared with omega-6 PUFAs. Decreased tumor growth and cachexia and increased survival previously reported for fish oil in Walker 256 tumor-bearing rats may be related to improved macrophage function rather than to improved T-cell function.

Ratio of n6 to n-3 fatty acids in the diet affects tumor growth and cachexia in Walker 256 tumor-bearing rats.

In this study we investigate the impact of the dietary ratio of n-6 to n-3 fatty acids (FAs) from postweaning until adult age upon tumor growth, lipid peroxidation in tumor tissue, and metabolic indicators of cancer cachexia in Walker 256 tumor-bearing rats. Weanling male Wistar rats received a normal low-fat (40 g/kg diet) chow diet or high-fat diets (300 g/kg) that included fish oil (FO) or sunflower oil or blends of FO and sunflower oil to yield n-6 to n-3 FA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, half of each group was inoculated with 1 ml of 2 x 10(7) Walker 256 cells. At the 14th day after tumor inoculation, the animals were killed, and tumors and blood were removed. The different diets did not modify the blood parameters in the absence of tumor bearing, except the high-FO diet, which decreased serum cholesterol and triacylglycerol concentrations. Tumor weight in chow-fed rats was 19 g, and these rats displayed cancer cachexia, characterized by hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, loss of body weight, and food intake reduction. Tumor weight in FO-fed rats was 7.7 g, and these animals gained body weight (14.6 g) and maintained blood metabolic parameters similar to non-tumor-bearing animals. Tumor weight in rats fed the diet with an n-6 to n-3 FA ratio of 6:1 was similar to tumor-bearing, chow-fed rats, but they gained 2 g in the body weight and blood metabolic parameters were similar to those in non-tumor-bearing rats. However, a further increase in the n-6 FA content of the diet did not change the cachectic state associated with tumor bearing. In this experimental model, a dietary n-6 to n-3 FA ratio of 6:1 was able to increase food intake and body weight, restore the biochemical blood parameters of cachexia, and prevent the development of cancer cachexia.