Glucose increases proliferation and chemoresistance in chronic myeloid leukemia via decreasing antioxidant Properties of ω-3 polyunsaturated fatty acids in the presence of Iron.

BACKGROUND: There is a strong association between hyperglycemia, oxidative stress, inflammation and the onset and progression of diabetes which causes a higher risk of cancer. This study investigated, the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements in hyper-glucose conditions on the K-562 cell line. METHODS: The effects of iron, ω-3 PUFAs, and a combination of both on K-562 cells were investigated under normal and high glucose conditions. The impact of these treatments was evaluated using multiple methodologies, including the MTT assay for cell viability, quantification of oxidative stress markers [total antioxidant capacity (TAC) and malondialdehyde (MDA)], and analysis of the cell cycle. Furthermore, the expression levels of TNFα and p53 mRNA were measured using Real-time PCR. RESULTS: The co-treatment of ω-3 PUFAs and iron in the presence of high glucose had notable effects, as evidenced by an increase in cell survival, resistance to imatinib chemotherapy, TNFαmRNA expression levels, MDA levels, and percentage of cells in the G2/S phase. Additionally, there was a decrease in the mRNA expression of p53 and TAC levels compared to treatment in the normal-glucose condition. CONCLUSION: Hyperglycemic conditions in conjunction with the combined treatment of theω-3 PUFAs and iron, led to reduced anticancer capacity, chemosensitivity, anti-inflammatory and antioxidant properties of the K-562 cells. These effects were found to be mediated by oxidative stress.

The anti-inflammatory effect of omega-3 polyunsaturated fatty acids dramatically decreases by iron in the hippocampus of diabetic rats.

AIMS: Receptor for advanced glycation end products (RAGE) production is induced by diabetes. Microglial cells are activated by RAGE and produce inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and oxidative stress markers. Persistent production of TNF-α can provide a link between diabetes and Alzheimer's disease (AD). The purpose of this study was to investigate the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements on microglial cell activation and inflammatory conditions in the hippocampus of type 2 diabetic rats. MAIN METHODS: Diabetic and normal Wistar rats were divided into six groups. Oxidative stress markers (total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA)), mRNA expression and protein levels of RAGE and TNF-α were evaluated in the hippocampus of the controls and supplemented with ferrous sulfate and ω-3 PUFAs alone and together rats. Also, the entry of microglia cells into the hippocampus was evaluated by immunohistochemistry technique. KEY FINDINGS: Levels of the microglial activation (2.4 fold, p < 0.0001), MDA (84%, p < 0.0001) and oxidative stress index (OSI) (11%, p = 0.0094), mRNA expression and protein contents of RAGE (1.83 fold and 82% respectively) and TNF-α (2.25 fold and 86% respectively) were strongly influenced by negative effect of iron compared to the group receiving only ω-3 PUFAs which was dramatically improved by vitamin E. SIGNIFICANCE: These observations indicated that the co-supplementation of ferrous sulfate with ω-3 PUFAs decreases the anti-inflammatory ability of ω-3 PUFAs in the hippocampus of diabetic rats via RAGE/TNF-α-induced oxidative stress pathway up-regulation.