Physical Training Protects Against Brain Toxicity in Mice Exposed to an Experimental Model of Glioblastoma.

Glioma 261 (Gl261) cell-mediated neurotoxicity has been reported in previous studies examining glioblastoma (GBM), and the effects of physical exercise (PE) on this neurotoxicity have been poorly investigated. This study aimed to evaluate the effects of a PE program in animals with experimental GBM. Male C57BL/6J mice were randomized into sham or GBM groups and subjected to a PE program for four weeks. Gl261 cells were administered into the intraventricular region at 48 h after the last exercise session. Body weight, water and feed consumption, and behavior were all evaluated for 21 days followed by euthanasia. The right parietal lobe was removed for the analysis of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), vimentin, C-myc, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), hydrogen peroxide, the glutathione system, and oxidative damage to proteins. The results revealed changes in the behavioral patterns of the trained animals, and no anatomopathological changes were observed in response to PE training. In contrast, animals with GBM subjected to PE exhibited lower immunoexpression of c-MYC, vimentin, and GFAP. Although experimental GBM altered the redox profile and inflammatory mediators, no significant alterations were observed after PE. In conclusion, our data provide consistent evidence of the relationship between PE and the improvement of tumorigenic parameters against the neurotoxicity of GL261 cells.

Neuroinflammatory Regulation of Gold Nanoparticles Conjugated to Ethylene Dicysteine Diethyl Ester in Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a demyelinating chronic autoimmune inflammatory disease of the central nervous system (CNS). A large amount of proinflammatory cytokines is released in the CNS from the self-reactive T cells infiltrate, leading to the destruction of the myelin sheath and contributing to the development of MS. Several drugs have emerged in recent years to treat MS, and studies have shown that gold nanoparticles (GNPs) have anti-inflammatory properties in autoimmune diseases. Thus, the effects of GNP conjugation to ethylene dicysteine diethyl ester (ECD) were evaluated in C57BL/6 female mice exposed to experimental MS. Animals were exposed to experimental autoimmune encephalitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG35-55) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis. The clinical and cerebral effects of the different doses of ECD-GNPs (0.3, 0.6, and 1.0 mg/kg) were first studied, and the results showed that the group treated with 0.6 mg/kg ECD-GNPs improved clinical symptoms, inflammatory infiltrate, and myelin integrity. In the following step, GNPs and ECD-GNPs (0.6 mg/kg) showed improvements in the clinical signs of the disease. Moreover, there was a reduction in the levels of proinflammatory cytokines in both groups compared to EAE, and only the isolated use of GNPs increased IL-4 expression. Both NF-κB and TGFß immunoexpression were significantly reduced following EAE + GNPs and EAE + ECD-GNPs treatment. In conclusion, GNPs and ECD-GNPs at 0.6 mg/kg attenuate the neurological signs of EAE likely due to inhibition of neuroinflammation induced by EAE.

Physical Exercise-Mediated Changes in Redox Profile Contribute to Muscle Remodeling After Passive Hand-Rolled Cornhusk Cigarette Smoke Exposure.

Consumption of non-traditional cigarettes has increased considerably worldwide, and they can induce skeletal muscle dysfunction. Physical exercise has been demonstrated to be important for prevention and treatment of smoking-related diseases. Therfore, the aim of this study was to investigate the effects of combined physical exercise (aerobic plus resistance exercise) on muscle histoarchitecture and oxidative stress in the animals exposed chronically to smoke from hand-rolled cornhusk cigarette (HRCC). Male Swiss mice were exposed to ambient air or passively to the smoke of 12 cigarettes over three daily sessions (four cigarettes per session) for 30 consecutive days with or without combined physical training. 48 h after the last training session, total leukocyte count was measured in bronchoalveolar lavage fluid (BALF), and the quadriceps were removed for histological/immunohistochemical analysis and measurement of oxidative stress parameters. The effects of HRCC on the number of leukocytes in BALF, muscle fiber diameter, central nuclei, and nuclear factor kappa B (NF-κB) were reverted after combined physical training. In addition, increased myogenic factor 5, tumor necrosis factor alpha (TNFα), reduced transforming growth factor beta (TGF-ß), and nitrate levels were observed after physical training. However, the reduction in superoxide dismutase and glutathione/glutathione oxidized ratio induced by HRCC was not affected by the training program. These results suggest the important changes in the skeletal muscle brought about by HRCC-induced alteration in the muscle redox profile. In addition, combined physical exercise contributes to remodeling without disrupting muscle morphology.

Leaf extracts of Campomanesia xanthocarpa positively regulates atherosclerotic-related protein expression.

Atherosclerosis is caused by a monocyte-mediated inflammatory process that, in turn, is stimulated by cytokines and adhesion molecules. Monocytes are then differentiated into macrophages, leading to the formation of arterial atherosclerotic plaques. Recently, guavirova leaf extracts from Campomanesia xanthocarpa (EG) have shown potential effects on the treatment of plaque formation by reducing cholesterol, LDL levels and serum oxidative stress. We evaluated the effect of EG on the viability of human monocytic and endothelial cell lines at three time points (24, 48 and 72 hours) and whether it can modulate the migration and in vitro expression of CD14, PECAM-1, ICAM-1, HLA-DR and CD105. Cell viability was affected only at higher concentrations and times. We observed decreased ICAM-1 expression in cells treated with 50 µg/ml EG and CD14 expression with IFN-γ and without IFN-γ. CD14 also decreased endothelial cell expression in the presence of IFN-γ and GE. We also found decreased expression of PECAM-1 when treated with EG and IFN-γ. In addition, EG-treated endothelial cells showed higher migration than the control group. Reduced expression of these markers and increased migration may lead to decreased cytokines, which may be contributing to decreased chronic inflammatory response during atherosclerosis and protecting endothelial integrity.

Yerba mate (Ilex paraguariensis St. Hil.) extract inhibits hand-rolled cornhusk cigarette smoke-induced oxidative pulmonary damage.

The aim of this study was to investigate the effects of yerba mate (Ilex paraguariensis St. Hil.) extract (YME) on oxidative stress parameters and pathological changes in the lungs of mice chronically exposed to hand-rolled cornhusk cigarette (HRC) smoke. Twenty-four male Swiss mice were divided into four groups exposed to the following treatments: control (ambient air), HRC, YME, and HRC plus YME. The animals were exposed to four HRCs per session, with 3 sessions/day, every day for 30 days. Twenty-four hours after the last inhalation, the mice were killed, and the left lungs were removed. The results showed that HRC contains elevated levels of tin and carbon oxide, but less arsenic, cobalt, manganese, and selenium than commercial cigarettes. YME administration reversed fibrosis, alveolar enlargement, and hemorrhage induced by HRC smoke. In addition, the YME and HRC significantly reduced the production of oxidants, oxidative damage and promoted a significant increase in total thiol. In conclusion, exposure to HRC smoke compromised pulmonary histoarchitecture by promoting structural changes and increasing oxidative stress in tissues. However, concomitant treatment with YME regulated the redox state and reduced the harmful effects of HRC smoke exposure in the lungs.