Novel insights into the application of recombinant mutated phospholipases D as antigens for developing new strategies against Loxoscelism.

Loxoscelism is the pathological condition triggered by a brown spider bite. The venom of these spiders is rich in phospholipases D (PLDs), which can induce virtually all local and systemic manifestations. Recombinant mutated PLDs from clinically relevant Loxosceles species in South America have been investigated as potential antigens to develop novel therapeutic strategies for loxoscelism. However, certain gaps need to be addressed before a clinical approach can be implemented. In this study, we examined the potential of these recombinant mutated PLDs as antigens by testing some variations in the immunization scheme. Furthermore, we evaluated the efficacy of the produced antibodies in neutralizing the nephrotoxicity and sphingomyelinase activity of brown spider venoms. Our findings indicate that the number of immunizations has a greater impact on the effectiveness of neutralization compared to the amount of antigen. Specifically, two or three doses were equally effective in reducing dermonecrosis and edema. Additionally, three immunizations proved to be more effective in neutralizing mice lethality than one or two. Moreover, immunizations mitigated the signs of kidney injury, a crucial aspect given that acute renal failure is a serious systemic complication. In vitro inhibition of the sphingomyelinase activity of Loxosceles venoms, a key factor in vivo toxicity, was nearly complete after incubation with antibodies raised against these antigens. These findings underscore the importance of implementing an effective immunization scheme with multiple immunizations, without the need for high antigen doses, and enhances the spectrum of neutralization exhibited by antibodies generated with these antigens. In summary, these results highlight the strong potential of these antigens for the development of new therapeutic strategies against cutaneous and systemic manifestations of loxoscelism.

Maternal periodontitis potentiates monosodium glutamate-obesity damage on Wistar offspring's fast-glycolytic muscle.

OBJECTIVE: To evaluate the effects of magnifying the damage caused by obesity induced by monosodium glutamate, using a model of maternal periodontitis, on the structure of the anterior tibialis muscle of the offspring. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into four experimental groups: control (n = 6), obese (n = 6), control with periodontitis (n = 6) and obese with periodontitis (n = 6). At 78 days of life, the rats were mated with males without any experimental intervention. The offspring of these rats (n = 1/L), at 120 days of life, were weighed and measured, then euthanized. Plasma was collected for analysis of cytokines IL-6, IL-10, IL-17 and TNF-α. Adipose tissues were collected and weighed, and the anterior tibial muscle was designated for histomorphological analyses (n = 6/group). RESULTS: Monosodium glutamate offspring showed significant muscle changes, such as a reduction in the size of fibres and neuromuscular junctions, and an increase in the nucleus and capillaries. However, all these changes were more expressed in monosodium glutamate-obese with periodontitis offspring. CONCLUSION: This leads us to suggest a magnifying effect promoted by periodontitis to the damage already well described by monosodium glutamate-obesity, determined by low-intensity inflammation, causing greater muscle damage.

How soon do metabolic alterations and oxidative distress precede the reduction of muscle mass and strength in Wistar rats in aging process?

Here we investigate metabolic changes, the antioxidant system and the accumulation of oxidative damage in muscles with different fiber types during the aging process in Wistar rats and try to map how sooner the changes occur. To do so, 30 male Wistar rats were submitted to behavioral evaluation to determine voluntary strength in the 11, 15, and 19 month old rats, measuring the energy metabolism, antioxidant system, oxidative damage and structure in the soleus and extensor digitorum longus muscles. We detected structural and metabolic changes in both muscles, especially in the EDL of 15 month old rats and in the soleus of 19 month old rats. In the 15 month old rats, there was a reduction in the cross-sectional area of the fibers, and a reduction in the proportion of type I fibers, accompanied by an increase in fiber density and the amount of type IIA fibers. This change in the fiber profile was followed by an increase in the activity of anaerobic metabolism enzymes, suggesting a reduction in the oxidative capacity of the muscle. In addition, there was an increase in the rate of lipid peroxidation, accompanied by a reduced antioxidant capacity. In the 19 month old rats, these disturbances got stronger. In summary, the present study demonstrated that before functional disturbances, there was an accumulation of oxidative damage and structural changes in the skeletal muscle beginning at 15 months old in the EDL and the soleus only in the biochemical parameters. Therefore, the metabolic alterations occurred at 15 months old and not before.

Regulation of Redox Profile and Genomic Instability by Physical Exercise Contributes to Neuroprotection in Mice with Experimental Glioblastoma.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training's effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

An Early and Sustained Inflammatory State Induces Muscle Changes and Establishes Obesogenic Characteristics in Wistar Rats Exposed to the MSG-Induced Obesity Model.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG induction of obesity upon systemic and muscular parameters of Wistar rats. The animals were exposed to MSG subcutaneously (4 mg·g-1 b.w.) or saline (1.25 mg·g-1 b.w.) daily from PND01 to PND05 (n = 24). Afterwards, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, increased adiposity, and inducted hyperinsulinemia and a pro-inflammatory scenario. In adulthood, the following were observed: peripheral insulin resistance, increased fibrosis, oxidative distress, and a reduction in muscle mass, oxidative capacity, and neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty restoring in the muscle profile is related to the metabolic damage established early on.

Whole-Body Vibration Promotes Skeletal Muscle Restructuring and Reduced Obesogenic Effect of MSG in Wistar Rats.

The negative changes of obesity to the locomotor system are a major concern in the current scenario, where obesity and metabolic syndrome are recurrent in Western societies. A physical exercise is an important tool as a way to rehabilitate obesity, highlighting whole-body vibration, as it is an easy-access modality with few restrictions. In this sense, we sought to evaluate the effect of whole-body vibration on the extensor digitorum longus muscle on a monosodium glutamate-induced obesity model. The main findings of the present study are related to the ability of the treatment with vibration to reduce the obesogenic characteristics and slow down the dyslipidemic condition of the animals. Likewise, the vibration promoted by the vibrating platform was essential in the recovery of the muscle structure, as well as the recovery of the muscle's oxidative capacity, initially compromised by obesity.

Development of a histopathological index for skeletal muscle analysis in Rattus norvegicus (Rodentia: Muridae).

Skeletal muscle histopathological changes induced or caused by pathologies in animal models, can impair functionality, being the main focus of therapeutic studies. This study aimed to propose a histopathological index to assess, in a quantitative manner, skeletal muscle changes induced by experimental protocols for Rodentia's models. For the development, evaluation of fit and parsimony, replicability, and sensitivity index, Wistar rats from experiments with the same experimental design, but with different variation factors, were used to achieve different levels of damage. The anterior tibial muscle of these animals was collected, processed histologically, and stained with hematoxylin and eosin. The adjustment and parsimony of the index were availed through Confirmatory Factor Analysis, reproducibility for evaluation of three people trained through the Intra-Class Correlation, and the discrimination capacity through a one-way ANOVA Test. We pointed out the adjustment for the proposed index while the ICC showed high reproducibility (n = 56; k = 3; ICC = 0.9790) and differences in the extent of damage between groups, following the hierarchical association promoted by experimental model stresses. The results show that the proposed index has a good fit and parsimony (χ2 = 426.34; p < 0.0001), in addition to being easily replicable by other researchers who know the morphology of muscle tissue and its morphological changes. It is worth mentioning that the development of tools that facilitate histopathological analysis, and that can quantitatively express the findings, are of great importance for the studies of regenerative science, reinforcing the relevance of this study.

Preventive treatment with fish oil facilitates the antidepressant-like effect of antidepressant drugs in type-1 diabetes mellitus rats: Implication of serotonergic system.

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment - FO plus antidepressants (FLX or IMI - both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.

Short- and Long-Term Effects of Dietary Supplementation with Fish Oil on Inflammatory Pain in Rats.

INTRODUCTION: Dietary supplementation with fish oil is promising as a complementary therapy for inflammatory pain. However, further studies are needed to support its therapeutic potential. For example, the antinociceptive effect of fish oil is widely suggested to be dependent on decreased prostaglandin E2 (PGE2) synthesis, but no previous study has investigated if it affects PGE2-induced nociceptive response. Similarly, beneficial long-term effects on inflammatory response are related to early exposure to fish oil, however, whether these effects include decreased inflammatory pain throughout life is not known. OBJECTIVE: The aim of this study was to investigate the short- and long-term effects of fish oil on inflammatory pain. METHODS: Dietary fish oil supplementation was performed through two protocols: in adult rats, during 20 days, or in dams, during pregnancy and lactation, with tests performed in adult offspring. The hyperalgesic response induced by carrageenan and its final mediators PGE2 and norepinephrine was used to model inflammatory pain. RESULTS: The findings demonstrated for the first time that dietary fish oil (1) decreases the hyperalgesia induced by carrageenan; (2) but not that induced by its final mediator PGE2 and norepinephrine; (3) increase omega-3 polyunsaturated fatty acids in peripheral neural tissue; and (4) attenuates inflammatory pain in individuals exposed to fish oil during pre-natal life and lactation. CONCLUSION: Together, these findings support that fish oil decreases inflammatory pain either when consumed during adult life or during prenatal development. Future studies should confirm the therapeutic potential of fish oil in humans, which is essential for the development of public policies to encourage a fish oil richer diet.

Nutrition and Cancercapsaicin Treatment Reduces Tumor Growth, Tumor Cell Proliferation Ex Vivo and Partially Reverses Cancer Cachexia in Walker 256 Tumor-Bearing Rats.

Capsaicin (trans-8-methyl-n-vanillyl-6-nonenamide) is the main pungent component found in hot peppers. AIM: In this study, we investigated the effect of capsaicin treatment on tumor growth and the metabolic indicators of cachexia in Walker 256 tumor-bearing rats. METHODS: Male Wistar rats were inoculated subcutaneously in the right flank with 1 ml of a sterile suspension of 3 × 107 Walker tumor cells. The treated groups received capsaicin intraperitoneal 5 mg/kg body weight for 13 days. RESULTS: The tumor weight on Day 14 in the non-treated group was 18 g. The rats also had a body weight loss, hypoglycemia, hyperlactacidemia, hypertriacylglycerolemia, and a depletion in glycogen storage. Treatment with capsaicin decreased tumor growth by 49% and a reversal of triacylglycerol serum. We also found a 32% reduction in tumor cell proliferation ex vivo. Lactate serum concentrations and body weight were lower but did not reach control levels. CONCLUSION: The treatment with capsaicin reduces tumor growth and cellular proliferation along with increased apoptosis and partial cachexia reversal.

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.

Wound healing treatment by high frequency ultrasound, microcurrent, and combined therapy modifies the immune response in rats

BACKGROUND: Therapeutic high-frequency ultrasound, microcurrent, and a combination of the two have been used as potential interventions in the soft tissue healing process, but little is known about their effect on the immune system. OBJECTIVE: To evaluate the effects of therapeutic high frequency ultrasound, microcurrent, and the combined therapy of the two on the size of the wound area, peritoneal macrophage function, CD4+ and CD8+, T lymphocyte populations, and plasma concentration of interleukins (ILs). METHOD: Sixty-five Wistar rats were randomized into five groups, as follows: uninjured control (C, group 1), lesion and no treatment (L, group 2), lesion treated with ultrasound (LU, group 3), lesion treated with microcurrent (LM, group 4), and lesion treated with combined therapy (LUM, group 5). For groups 3, 4 and 5, treatment was initiated 24 hours after surgery under anesthesia and each group was allocated into three different subgroups (n=5) to allow for the use of the different therapy resources at on days 3, 7 and 14 Photoplanimetry was performed daily. After euthanasia, blood was collected for immune analysis. RESULTS: Ultrasound increased the phagocytic capacity and the production of nitric oxide by macrophages and induced the reduction of CD4+ cells, the CD4+/CD8+ ratio, and the plasma concentration of IL-1β. Microcurrent and combined therapy decreased the production of superoxide anion, nitric oxide, CD4+-positive cells, the CD4+/CD8+ ratio, and IL-1β concentration. CONCLUSIONS: Therapeutic high-frequency ultrasound, microcurrent, and combined therapy changed the activity of the innate and adaptive immune system during healing process but did not accelerate the closure of the wound.

Wound healing treatment by high frequency ultrasound, microcurrent, and combined therapy modifies the immune response in rats.

BACKGROUND: Therapeutic high-frequency ultrasound, microcurrent, and a combination of the two have been used as potential interventions in the soft tissue healing process, but little is known about their effect on the immune system. OBJECTIVE: To evaluate the effects of therapeutic high frequency ultrasound, microcurrent, and the combined therapy of the two on the size of the wound area, peritoneal macrophage function, CD4+ and CD8+, T lymphocyte populations, and plasma concentration of interleukins (ILs). METHOD: Sixty-five Wistar rats were randomized into five groups, as follows: uninjured control (C, group 1), lesion and no treatment (L, group 2), lesion treated with ultrasound (LU, group 3), lesion treated with microcurrent (LM, group 4), and lesion treated with combined therapy (LUM, group 5). For groups 3, 4 and 5, treatment was initiated 24 hours after surgery under anesthesia and each group was allocated into three different subgroups (n=5) to allow for the use of the different therapy resources at on days 3, 7 and 14 Photoplanimetry was performed daily. After euthanasia, blood was collected for immune analysis. RESULTS: Ultrasound increased the phagocytic capacity and the production of nitric oxide by macrophages and induced the reduction of CD4+ cells, the CD4+/CD8+ ratio, and the plasma concentration of IL-1ß. Microcurrent and combined therapy decreased the production of superoxide anion, nitric oxide, CD4+-positive cells, the CD4+/CD8+ ratio, and IL-1ß concentration. CONCLUSIONS: Therapeutic high-frequency ultrasound, microcurrent, and combined therapy changed the activity of the innate and adaptive immune system during healing process but did not accelerate the closure of the wound.

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.

Fish oil decreases C-reactive protein/albumin ratio improving nutritional prognosis and plasma fatty acid profile in colorectal cancer patients.

Previous studies have shown that n-3 polyunsaturated fatty acids n-3 (n-3 PUFA) have several anticancer effects, especially attributed to their ability to modulate a variety of genomic and immune responses. In this context, this randomized, prospective, controlled clinical trial was conducted in order to check whether supplementation of 2 g/day of fish oil for 9 weeks alters the production of inflammatory markers, the plasma fatty acid profile and the nutritional status in patients with colorectal cancer (CRC). Eleven adults with CRC in chemotherapy were randomized into two groups: (a) supplemented (SG) daily with 2 g/day of encapsulated fish oil [providing 600 mg/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] for 9 weeks (n = 6), and (b) control (CG) (n = 5). All outcomes were evaluated on the day before the first chemotherapy session and 9 weeks later. Plasma TNF-α, IL-1ß, IL-10 and IL-17A, the pro/anti-inflammatory balance (ratio TNF-α/IL-10 and IL-1ß/IL10) and serum albumin, showed no significant changes between times and study groups (p > 0.05). C-reactive protein (CRP) and the CRP/albumin ratio showed opposite behavior in groups, significantly reducing their values in SG (p < 0.05). Plasma proportions of EPA and DHA increased 1.8 and 1.4 times, respectively, while the ARA reduced approximately 0.6 times with the supplementation (9 weeks vs baseline, p < 0.05). Patients from SG gained 1.2 kg (median) while the CG lost -0.5 kg (median) during the 9 weeks of chemotherapy (p = 0.72). These results demonstrate that 2 g/day of fish oil for 9 weeks of chemotherapy improves CRP values, CRP/albumin status, plasma fatty acid profile and potentially prevents weight loss during treatment.

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.

Bax/Bcl-2 protein expression ratio and leukocyte function are related to reduction of Walker-256 tumor growth after ß-hydroxy-ß-methylbutyrate (HMB) administration in Wistar rats.

This study investigated the mechanisms by which ß-hydroxy-ß-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 × 10(7)/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 H(2)O(2) 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.

Fish oil supplementation improves neutrophil function during cancer chemotherapy.

Cancer chemotherapy is associated with neutropenia and impaired neutrophil function. This study aimed to investigate whether supplementation with low dose fish oil (FO), providing n-3 polyunsaturated fatty acids, in cancer patients receiving chemotherapy after surgical tumor (mainly gastrointestinal) removal is able to improve the function of blood neutrophils. Patients (n = 38) receiving chemotherapy (5-fluorouracil and leucovorin) were randomized into two groups; one group (control) did not receive a supplement, while the other group (FO) received 2 g FO/day for 8 weeks; the FO provided 0.3 g eicosapentaenoic acid plus 0.4 g docosahexaenoic acid per day. Patients in the control group lost an average of 2.5 kg of weight over the 8 weeks of the study. The number of blood polymorphonuclear cells (PMNC), mainly neutrophils, and their functions (phagocytosis and hydrogen peroxide production) decreased in the control group (average decreases of approximately 30, 45 and 17%, respectively). FO prevented these decreases and actually increased body weight (average of 1.7 kg weight gain; p < 0.002 vs. control group), PMNC number (average 29% increase), phagocytosis (average 14% increase) and superoxide production (average 28% increase). FO may be useful in preventing chemotherapy-induced decline in neutrophil number and function.

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.