Hyperglycaemia is a major cause of pathophysiological processes such as oxidative stress, inflammation, and apoptosis in diabetes. Dapagliflozin (DAPA), a novel hypoglycaemic drug, has been shown to have anti-apoptotic, anti-inflammatory, and antioxidant effects in multiple experimental studies. In this study, we investigated the protective effects of DAPA in the hyperglycaemic condition to identify associated molecular mechanisms. human umbilical vein endothelial cells (HUVEC) endothelial cells were treated with 40 mM glucose for 72 h to establish an in vitro high glucose (HG) condition model, and then additional groups co-treated with or without DAPA before glucose treatment. Then, cell viability, reactive oxygen species (ROS), proinflammatory cytokines (IL-6 and TNF-α), apoptosis, and SIRT1 expression were measured. The results showed that DAPA pretreatment resulted in increased cell viability.Additionally, DAPA pretreatment decreased endothelial ROS, IL-6, and TNF-α levels in endothelial cells subjected to HG conditions. Moreover, DAPA pretreatment significantly prevented HG-induced apoptosis and caspase-3 activity in HUVECs. Furthermore, DAPA increased the expression of SIRT1, PGC-1α, and increased the phosphorylation levels of AMPK (p-AMPK) in a set of HG conditions in HUVECs.However, the endothelial protective effects of DAPA were abolished when cells were subjected to the SIRT1 inhibitor (EX-527) and AMPK inhibitor (Compound C).These findings suggest that DAPA can abrogate HG-induced endothelial cell dysfunction by AMPK/SIRT1 pathway up-regulation. Therefore, suggesting that the activation of AMPK/SIRT1 axis by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.
Background
The main aim of this study was to assess the serum levels of copper (Cu), zinc (Zn) with lipid peroxidation, Cu/Zn superoxide dismutase (Cu/Zn SOD) activity, and ceruloplasmin (Cp) in multiple myeloma (MM) patients.
Materials and methods
The study was conducted in 34 MM patients at stage I. Serum Cu and Zn levels were measured by atomic absorption spectrometry. Also, spectrophotometric assays of malondialdehyde (MDA) levels in addition to Cp and Cu/Zn SOD were quantitated.
Results
The results showed a significant decrease in the serum Zn levels in patients with MM (p < 0.0001). Also, serum Cu levels were significantly higher (p < 0.0001). However, the serum Cu/Zn ratio was significantly higher in the cancer patients (p < 0.0001). A significant difference was observed in the patients group compared with the control group according to the Cu/Zn SOD activity (p < 0.0001). Moreover, serum levels of Cp and MDA were significantly increased in patients (p < 0.0001, both).
Conclusions
The elevated levels of serum Cu and MDA with a decrease in Zn and Cu/Zn SOD might explain the increased oxidative stress in MM disease. As the high Cu level was observed in MM patients, therefore, Cu levels should be concentrated in the pathogenesis and progression of MM disease.
Objective Oxidants include important active molecules which are created in the body and attack biological molecules especially lipids, carbohydrates, nucleic acids and proteins, and cause oxidation and various diseases in the body. Antioxidants existing in the body help to avoid the incidence of these injuries. Pregnant women are among those where oxidation of biological molecules may do irreparable damage to them and their embryos. So, the purpose of this study was to review the effect of folic acid with both high (5 mg/day) and low (0.5 mg/day) doses on the changes of oxidative protein in reducing plasma homocystein concentration during pregnancy. Materials and methods Forty-five pregnant women participated in this study. They were divided into two groups: group 1 included 23 women who received 5 mg/day folic acid and group 2 included 23 women who took 0.5 mg/day folic acid before pregnancy till the 36th week pregnancy. We measured the biochemical variables in the serum of pregnant women at the beginning and at the end of the study. Results Folic acid reduced plasma homocytein in both low and high dose groups (p = 0.035, p = 0.012, respectively). Also, the results showed that folic acid prescription led to reduce plasma level of carbonyl groups in both low and high dose groups (p = 0.01, p = 0.03, respectively). Furthermore, the results showed that there is no significant difference between two groups and folic acid affects both groups equally. Conclusion It is possible that folic acid administration can reduce plasma homocysteine and carbonyl levels during pregnancy in dose independent manner.
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