Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis.

Background: Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. Aim: We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. Methodology: A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. Results: In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. Conclusion: The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.

Differential effects of whole blood heat treatment on the ex vivo inflammatory profile of untrained and trained men.

This study evaluated the effects of heat stress on the ex vivo inflammatory profile in untrained and trained men. Whole blood samples from untrained (UT) and trained (TR) individuals were incubated for 2 h at 37 °C or 40 °C. The whole blood of a subsample of the participants (n = 5 in both TR and UT groups) were stimulated with lipopolysaccharide (LPS, 10 ng/mL) concomitant to heat treatment (37 °C versus 40 °C). Flow cytometry was used to assess the intracellular NF-κB activation in CD4+ T cells and CD14+ monocytes, the expression of Toll-Like Receptor-4 (TLR-4), the frequencies of CD4+CD25-CD39+ and CD4+CD25+CD39+ T cells and monocyte subsets (CD14+CD16-; CD14+CD16+; CD14-CD16+), the mitochondrial membrane potential (MMP) and the reactive oxygen species (ROS) production by lymphocytes and monocytes. The production of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) by LPS-stimulated whole blood were also evaluated. Heat treatment (40 °C) increased the proportions of CD14+CD16- and CD14+CD16+ monocytes and the lymphocyte MMP in the UT group. The frequencies of CD14-CD16+ monocytes and the activation of NF-κB in CD14+ monocytes decreased in UT and TR groups after heat treatment, while a reduction in CD4+CD25-CD39+ T-cells was observed only in the UT group. Higher TLR-4 and NF-κB activation were found in LPS-stimulated monocytes of UT men concomitant with higher TNF-α production and diminished IL-10 production after heat treatment. TR individuals presented lower NF- κB activation in LPS-stimulated monocytes after heat treatment. Our data suggest that the training status of individuals may impact on the anti-inflammatory response of heat treatment.

DNA damage in mononuclear cells following maximal exercise in sedentary and physically active lean and obese men.

We evaluated the impact of maximal exercise on oxidative stress and DNA damage in peripheral blood mononuclear cells (PBMC) from sedentary and exercised lean and obese men. PBMC were collected before, immediately and 1-h after exercise and exposed to hydrogen peroxide (H2O2; 25 and 50 µM, 4 h). A leukocytosis was induced by maximal exercise immediately and 1-h after exercise in all groups. However, a lymphopenia was observed 1-h after exercise in the Sedentary obese group. In the control condition, low DNA damage index concomitant to increases in intracellular glutathione content (GSH) was identified immediately after exercise in all groups. However, higher DNA damage index and lipid peroxidation occurred 1-h after the bout in Sedentary and Exercised Obese groups. PBMC exposed to both H2O2 25 and 50 µM experienced higher DNA damage and lipid peroxidation index immediately after exercise in all groups. Both lipid peroxidation and DNA damage index remained higher in PBMC of Sedentary Lean, Sedentary Obese, and Exercised obese groups obtained 1-h after exercise in both H2O2 25 and 50 µM, with the highest values identified in PBMC from Sedentary Obese group. However, increases in GSH content were identified in treated PBMC from sedentary and exercised lean groups as well as exercised obese group 1-h after exercise. Habitual exercise confers increased resistance of PBMC to DNA damage induced by oxidative stress, reducing the detrimental effects of obesity.Keywords: Exercise, physical activity, DNA damage, obesity, mutagenesis, oxidative stress.

Immunoregulation induced by autologous serum collected after acute exercise in obese men: a randomized cross-over trial.

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts-high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue-in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

Blood flow restriction impairs the inflammatory adaptations of strength training in overweight men: a clinical randomized trial.

The aim of this study was to evaluate the impact of high-intensity strength training (ST) or low-intensity strength training with blood flow restriction (ST-BFR) on monocyte subsets, the expression of C-C chemokine receptor 5 (CCR5), and CD16 on monocytes, and tumor necrosis factor alpha (TNF-α) production of overweight men. Thirty overweight men were randomly assigned to conventional ST or ST-BFR. Both groups performed exercises of knee extension and biceps curl with equal volume (3 sessions/week) over 8 weeks, and the peripheral frequency of monocytes (CD14+CD16-, classical monocytes; CD14+CD16+, intermediate monocytes; CD14-CD16+, nonclassical monocytes), the mean fluorescence intensity (MFI) of CCR5 and CD16 on CD14+ monocytes; and the production of TNF-α by lipopolysaccharide (LPS)-stimulated cells were quantified. Eight weeks of ST increased the frequency of CD14+CD16- monocytes (p = 0.04) and reduced the percentage of CD14-CD16+ (p = 0.02) and the production of TNF-α by LPS-stimulated cells (p = 0.03). The MFI of CD16 on CD14+ monocytes decreased after the ST intervention (p = 0.02). No difference in monocyte subsets, CCR5 or CD16 expression, and TNF-α production were identified after ST-BFR intervention (p > 0.05). The adoption of ST promotes anti-inflammatory effects on monocyte subsets of overweight men, but this effect was lost when BFR was adopted. Novelty High-intensity strength training reduces the production of TNF-α and the peripheral frequency of CD16+ monocytes in overweight men. Blood flow restriction method blunts the strength training adaptations on monocyte subsets and pro-inflammatory TNF-α production in overweight men.

Exercise-induced BDNF production by mononuclear cells of sedentary and physically active obese men.

BACKGROUND: Obesity and low physical activity changes the redox state and neurotrophin secretion by leukocytes. However, the role of exercise on brain derived neurotrophic factor (BDNF) production and oxidative stress markers of peripheral blood mononuclear cells (PBMC) remains unknown. This study aimed to verify the impact of acute maximal exercise on oxidative stress markers and the BDNF production by stimulated PBMC from sedentary and physically active obese men. METHODS: PBMC from twelve sedentary obese (SED group) and twelve regular exercisers (EXE group) obese men were collected before, immediately and 1-h after maximal exercise. PBMC were stimulated with lipopolysaccharide (LPS) to evaluate the BDNF and nitrite production, lipid peroxidation, and antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activities. RESULTS: PBMC from EXE group presented higher BDNF production (P=0.03) and lower TBARS levels than SED group at baseline. Maximal exercise increased BDNF and nitrite production, and lipid peroxidation immediately and 1-h after the bout in both groups. The EXE group presented higher superoxide dismutase activity immediately after bout and higher catalase activity 1-h after bout in PBMC. On the other hand, PBMC from SED group had lower superoxide dismutase activity immediately after exercise. Furthermore, PBMC from EXE group presented higher BDNF production and SOD activity and lower TBARS concentrations than SED group immediately after maximal exercise. CONCLUSIONS: Maximal exercise changes the redox state and enhances BDNF production by LPS-stimulated PBMC in obese individuals.