Oxidative stress has an important role in neuronal damage during cerebral ischemia and can lead to cognitive and behavioral impairment. Alpha-tocopherol, a powerful antioxidant, may be able to preserve neuronal tissue and circumvent neurological deficits. Thus, this study aimed to investigate the influence of alpha-tocopherol in the preservation of brain tissue and the maintenance of memory formation in stroke-prone spontaneously hypertensive rats (SHRSP). To achieve this aim, twenty-four 15-week-old male SHRSP rats were separated into the following four groups (n = 6 each) that received different treatments over a 4-week period: the alpha-tocopherol group, the control group, the L-NAME group, and the L-NAME + alpha-tocopherol group. We evaluated the physiological parameters (body weight, diuresis, and food and water intake), an oxidative stress marker (malondialdehyde levels), and neurological responses (the Morris Water Maze and Novel Objects Recognition tests). Afterwards, the brains were removed for histopathological analysis and quantification of the number of cells in the hippocampus. Statistically, the alpha-tocopherol group demonstrated better results when compared to all groups. The data indicated a reduction in oxidative stress and the preservation of neurological responses in groups treated with alpha-tocopherol. In contrast, the L-NAME group exhibited increased malondialdehyde levels, impairment of neurological responses, and several hippocampus tissue injuries. The others groups exhibited nerve tissue changes that were restricted to the glial nodes. No significant alterations were observed in the physiologic parameters. Based on these findings, we suggest that alpha-tocopherol can prevent stroke, preserve the structure of the hippocampus, and maintain both memory and cognition functions.
The effects of radiation are known to be potentiated by N‐3 polyunsaturated fatty acids, which modulate several signaling pathways, but the molecular mechanisms through which these fatty acids enhance the anticancer effects of irradiation in colorectal cancer (CRC) treatment remain poorly elucidated. Here, we aimed to ascertain whether the fatty acid docosahexaenoic acid (DHA) exerts a modulating effect on the response elicited by radiation treatment (RT). Two CRC cell lines, Caco‐2 and HT‐29, were exposed to RT, DHA, or both (DHA + RT) for various times, and then cell viability, proliferation, and clonogenicity were assessed. Moreover, cell cycle, apoptosis, and necrosis were analyzed using flow cytometry, and the involvement of WNT/β‐catenin signaling was investigated by immunofluorescence to determine nuclear β‐catenin, GSK3β phosphorylation status, and TCF/LEF‐activity reporter. DHA and RT applied separately diminished the viability of both HT‐29 and Caco‐2 cells, and DHA + RT caused a further reduction in proliferation mainly in HT‐29 cells, particularly in terms of colony formation. Concomitantly, our results verified cell cycle arrest in G0/G1 phase, a reduction of cyclin D1 expression, and a decrease in GSK3β phosphorylation after the combined treatment. Furthermore, immunofluorescence quantification revealed that nuclear β‐catenin was increased in RT‐exposed cells, but this effect was abrogated in cells exposed to DHA + RT, and the results of TCF/LEF‐activity assays confirmed that DHA attenuated the increase in nuclear β‐catenin activity induced by irradiation. Our finding shows that DHA applied in combination with RT enhanced the antitumor effects of irradiation on CRC cells, and that the underlying mechanism involved the WNT/β‐catenin pathway. © 2018 BioFactors, 45(1):24–34, 2019
Decylubiquinone treatment in vitro has demonstrated a potent inhibitor effect on reactive oxidative species production. However, the effectin vivo has not been demonstrated yet. Thus, rats SHRSP male were divided in two groups: treated and controls (n=6, each). The treated group received 10 mg/Kg(-)/body weight of decylubiquinone diluted in coconut oil by oral gavage during four weeks. Control rats just received the vehicle. Body weight, diuresis, food and water intake, systolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood glucose levels and malondialdehyde were determined. There were a significant (p<0.05) reduction on systolic blood pressure, plasma malondialdehyde, total cholesterol and LDL-cholesterol in the treated group. Additionally, HDL-cholesterol also increased significantly. However, body weight, diuresis, food and water intake, blood glucose levels and triglycerides did not alter after treatment. Thus, decylubiquinone can be a new antihypertensive, hypolipidemic and antioxidant agent on the prevention and treatment of diseases linked to oxidative stress.
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