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Omega-3 fatty acids modulate cyclophosphamide induced markers of immunosuppression and oxidative stress in pigs.

ABSTRACT: Immunosuppression directly correlates with economic benefits in livestock. Although omega-3, known as an energy source, is used as a pharmaceutical molecule, it remains unknown whether dietary supplementation with omega-3 can alleviate cyclophosphamide-induced immunosuppression in pigs. Omega-3 treatment increased the number of white blood cell, lymphocytes, and monocytes and decreased tumor necrosis factor (TNF)-? production under CTX challenge. In addition, we confirmed that omega-3 decreased the expression of nuclear factor (NF)-?B, TNF-?, interferon (IFN)-?, and interleukin (IL)-8 in peripheral blood mononuclear cells. Additionally, omega-3 alleviated the activities of liver injury markers (alanine transaminase [ALT] and aspartate transaminase [AST]) and modulated oxidative stress markers (superoxide dismutase [SOD], malondialdehyde [MDA], and glutathione peroxidase [GPx]) in the blood serum after the CTX challenge. Based on these results, we suggest that omega-3 treatment modulates CTX-induced immunosuppression and oxidative stress in pigs. These results may have important implications in the development of new therapeutic approaches to improve immunosuppression, hepatic injury and dysfunction, and oxidative stress in pigs.

SUBMITTER: Lee SI

PROVIDER: S-EPMC6389924 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Project description:ObjectiveOmega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms.Methods and resultsWe determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells. Immunofluorescence staining showed that γ-H2AX foci formation, a prominent marker of DNA damage, was significantly reduced in the cells treated with EPA and DHA (by 47% and 48%, respectively). H2O2-induced activation of ATM, a major kinase orchestrating DNA damage response, was significantly reduced with EPA and DHA treatment (by 31% and 33%, respectively). These results indicated EPA and DHA attenuated DNA damage independently of the DNA damage response. Thus the effects of EPA and DHA on a source of DNA damage were examined. EPA and DHA significantly reduced intracellular reactive oxygen species under both basal condition and H2O2 stimulation. In addition, the mRNA levels of antioxidant molecules, such as heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain and manganese superoxide dismutase, were significantly increased with EPA and DHA. Silencing nuclear factor erythroid 2-related factor 2 (NRF2) remarkably abrogated the increases in mRNA levels of antioxidant molecules and the decrease in intracellular reactive oxygen species. Furthermore, EPA and DHA significantly reduced H2O2-induced senescence-associated β-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing.ConclusionsOur results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of NRF2-mediated antioxidant response. Therefore omega-3 fatty acids likely help prevent cardiovascular disease, at least in part, by their genome protective properties.

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Omega-3 fatty acids modulate cyclophosphamide induced markers of immunosuppression and oxidative stress in pigs.

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