Katya Naliwaiko

Depression in Parkinson's disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation.

BACKGROUND Effect of fish oil supplementation in parkinsonian patients with depression measured by Montgomery-Asberg Rating Scale (MADRS), the Clinical Global Impressions Scale (CGI) and Beck Depression Inventory (BECK). METHOD Double-blind, placebo-controlled study analyzed depression in 31 patients with Parkinsons Disease and Major Depression (DSM-IV). The patients were double-blind separated in 2 groups that received fish oil (containing omega-3 fatty acids) or mineral oil capsules for 3 months; each group was separated in 2 new groups: one taking antidepressant medication and another one not taking it. RESULTS 29 patients completed the 12-week trial, 58% were female and the mean age was 64.4 years old. Patients supplemented with fish oil showed a significant decrease in MADRS and CGI-Depression scores, and there was no difference among groups in BDI. 14 patients (42%) met criteria for > or = 50% reduction in MADRS score, 7 patients (22%) met criteria for remission (final MADRS total score < or = 12), and 2 patients (6%) discontinued supplementation of fish oil. HPLC analysis of fatty-acid profile showed increase of omega-3 fatty acid in the erythrocyte membrane of patients taking fish oil. CONCLUSION These results reveal that PD patients taking fish oil, with or without antidepressants, presented improvement in depressive symptoms and indicate that the intake of omega-3 can be used with an antidepressant effect or as adjuvant therapy with some other medication. This is a first pilot study with parkinsonian patients and omega-3 supplementation and requires replication in a larger sample.

Fish-oil supplementation enhances the effects of strength training in elderly women

BACKGROUND Muscle force and functional capacity generally decrease with aging in the older population, although this effect can be reversed, attenuated, or both through strength training. Fish oil (FO), which is rich in n-3 (omega-3) PUFAs, has been shown to play a role in the plasma membrane and cell function of muscles, which may enhance the benefits of training. The effect of strength training and FO supplementation on the neuromuscular system of the elderly has not been investigated. OBJECTIVE The objective was to investigate the chronic effect of FO supplementation and strength training on the neuromuscular system (muscle strength and functional capacity) of older women. DESIGN Forty-five women (aged 64 ± 1.4 y) were randomly assigned to 3 groups. One group performed strength training only (ST group) for 90 d, whereas the others performed the same strength-training program and received FO supplementation (2 g/d) for 90 d (ST90 group) or for 150 d (ST150 group; supplemented 60 d before training). Muscle strength and functional capacity were assessed before and after the training period. RESULTS No differences in the pretraining period were found between groups for any of the variables. The peak torque and rate of torque development for all muscles (knee flexor and extensor, plantar and dorsiflexor) increased from pre- to posttraining in all groups. However, the effect was greater in the ST90 and ST150 groups than in the ST group. The activation level and electromechanical delay of the muscles changed from pre- to posttraining only for the ST90 and ST150 groups. Chair-rising performance in the FO groups was higher than in the ST group. CONCLUSIONS Strength training increased muscle strength in elderly women. The inclusion of FO supplementation caused greater improvements in muscle strength and functional capacity.

The antidepressant role of dietary long-chain polyunsaturated n-3 fatty acids in two phases in the developing brain

In this work we investigated the effect from fish oil (FO) supplementation, rich in n-3 fatty acids, on an antidepressant effect on adult rats in Phase A (supplementation during pregnancy and lactation) and phase B (supplementation during post-weaning until adulthood). During Phase A, female rats, used as matrix to obtain male rats, were divided in three groups: FO (daily supplemented), CF (coconut fat daily supplemented) and control (not supplemented). Our results showed that adult rats whose mothers were supplemented with FO during Phase A and rats supplemented during phase B demonstrated a significantly decreased immobility time when compared to control and CF groups. There was no difference in neither motor activity nor anxiety behavior in the three groups excluding false positive results. Our results suggest that n-3 fatty acids supplementation during Phases A and B had a beneficial effect on preventing the development of depression-like behavior in adult rats.

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

Abstract: 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 × 107 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.

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

BackgroundObesity 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.MethodsMonosodium 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.ResultsObese 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.ConclusionsLow 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.

Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: a pharmacological investigation.

Accidents involving Brown spider (Loxosceles sp.) venom produce a massive inflammatory response in injured region. This venom has a complex mixture of different toxins, and the dermonecrotic toxin is the major contributor to toxic effects. The ability of Loxosceles intermedia venom and a recombinant isoform of dermonecrotic toxin to induce edema and increase in vascular permeability was investigated. These toxins were injected into hind paws and caused a marked dose and time-dependent edema and increase in vascular permeability in mice. Furthermore, the enzymatic activity of venom toxins may be primal for these effects. A mutated recombinant isoform of dermonecrotic toxin, that has only residual enzymatic activity, was not able to induce these inflammatory events. Besides the previous heating of toxins markedly reduced the paw edema and vascular permeability showing that thermolabile constituents can trigger these effects. In addition, the ability of these venom toxins to evoke inflammatory events was partially reduced in compound 48/80-pretreated animals, suggesting that mast cells may be involved in these responses. Pretreating mice with histamine (prometazine and cetirizine) and serotonin (methysergide) receptor antagonists significantly attenuated toxins induced edema and vascular permeability. Moreover, HPLC analysis of whole venom showed the presence of histamine sufficient to induce inflammatory responses. In conclusion, these inflammatory events may result from the activation of mast cells, which in turn release bioamines and may be related to intrinsic histamine content of venom.

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

BackgroundShark 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.MethodsWeanling 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.ResultsFourteen 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.ConclusionsSLOil 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.

Guanosine promotes B16F10 melanoma cell differentiation through PKC–ERK 1/2 pathway

Malignant melanoma is one of the most lethal cancers. Nowadays, several anti-melanoma therapies have been employed. However, the poor prognosis and/or the increased toxicity of those treatments clearly demonstrate the requirement of searching for new drugs or novel combined chemotherapeutic protocols, contemplating both effectiveness and low toxicity. Guanosine (Guo) has been used in combination with acriflavina to potentiate the latters antitumor activity, through still unknown mechanisms. Here, we show that Guo induces B16F10 melanoma cell differentiation, attested by growth arrest, dendrite-like outgrowth and increased melanogenesis, and also reduced motility. A sustained ERK 1/2 phosphorylation was observed after Guo treatment and ERK inhibition led to blockage of dendritogenesis. Intracellular cyclic AMP was not involved in ERK activation, since its levels remained unchanged. Protein kinase C (PKC), in contrast to phospholipase C (PLC), inhibition completely prevented ERK activation. While the classical melanoma differentiation agent forskolin activates cAMP-PKA-Raf-MEK-ERK pathway in B16F10 cells, here we suggest that a cAMP-independent, PKC-ERK axis is involved in Guo-induced B16F10 differentiation. Altogether, our results show that Guo acts as a differentiating agent, with cytostatic rather than cytotoxic properties, leading to a decreased melanoma malignancy. Thus, we propose that Guo may be envisaged in combination with lower doses of conventional anti-melanoma drugs, in an attempt to prevent or diminish their adverse effects.

Walker-256 tumor growth is inhibited by the independent or associative chronic ingestion of shark liver and fish oil: a response linked by the increment of peritoneal macrophages nitrite production in Wistar rats

Fish oil (FO) is widely known by its capacity to positively modulate immune parameters and decrease the growth of some tumors. Despite the enormous number of studies addressing the effects of FO, there are few reports showing similar results using other marine sources of lipid compounds with biologic importance. This study aimed to compare the effects of shark liver oil (SLO), which is a source of omega-3 fatty acids and alkylglycerols, with those obtained with FO administration, or the association of both, on tumor growth and the innate immune system in Walker-256 tumor-bearing rats. Beginning at 21 days of age, Wistar rats were fed regular chow and/or FO and/or SLO supplement (1 g/kg body weight per day) for 14 weeks. Walker-256 tumor cells were inoculated on the 90th day. As expected, 14 days after inoculation, rats fed with FO presented tumor weights that were 50% lower than the control tumors (P < .05). The association of both FO and SLO and ingestion of SLO alone also reached the same reduction level. Except for adhesion, all macrophage parameters assayed were 200% higher in rats fed with FO and those supplemented with both FO and SLO compared with control rats. Only reactive nitrogen species production was increased by SLO. These results suggest that SLO might also have indirect antitumor properties. Conversely, there were no additive effects when SLO was administered with FO. Therefore, SLO is another marine compound with in vivo antitumor effects, but its action mechanisms seem not to be related to major modifications on macrophage function.

Bax/Bcl-2 Protein Expression Ratio and Leukocyte Function Are Related to Reduction of Walker-256 Tumor Growth After β-Hydroxy-β-Methylbutyrate (HMB) Administration in Wistar Rats

This study investigated the mechanisms by which β-hydroxy-β-methylbutyrate (HMB) administration in rats reduces Walker-256 tumor growth. Male Wistar rats were supplemented with HMB (76 mg/kg/day) (HW), or a placebo (W), during 8 wk by gavage. At the 6th wk, rats were inoculated with a suspension of Walker 256 tumor cells (3 × 107/mL). Fifteen days after inoculation, the HW group showed higher glycemia (109.4 ± 5.53 vs. 89.87 ± 7.02 mg/dL, P < 0.05) and lower spleen (1.35 ± 0.05 vs. 1.65 ± 0.12 g, P < 0.05) and tumor weights (9.64 ± 1.07 vs. 13.55 ± 1.19 g, P < 0.05) compared to the W group. Tumor cells extracted from the HMB-treated rats displayed a 36.9% decrement in rates of proliferation ex vivo and a significant increase in the Bax/Bcl-2 protein expression ratio in comparison to those extracted from the placebo-treated rats (P < 0.05). Both phagocytic capacity and H2O2 production rates were higher in polymorphnuclear cells that were obtained from the blood of the HW rats in comparison to those from the W rats (P < 0.05). Reduction of necrotic regions and an intense infiltration of leukocytes and activated granulocytes in HW were evident by transmission electron microscopy. Our findings suggest that HMB supplementation decreases tumor burden by modifying the inner environment of tumor cells and by interfering with blood leukocyte function.