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Aims/Introduction  Recent studies advocate that omega‐3 polyunsaturated fatty acids (ω‐3  PUFA s) have direct anti‐oxidative and anti‐inflammatory effects in the vasculature; however, the role of ω‐3  PUFA s in Schwann cells remains undetermined.    Materials and methods  Immortalized mouse Schwann ( IMS 32) cells were incubated with the ω‐3  PUFA s docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ). The messenger ribonucleic acid levels of several anti‐oxidant enzymes (heme oxygenase‐1 [Ho‐1], nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1, catalase, superoxide dismutase and glutathione peroxidase) were identified using real‐time reverse transcription polymerase chain reaction. Ho‐1 and nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1 protein levels were evaluated using Western blotting. Nuclear factor (erythroid‐derived 2)‐related factor 2 (Nrf2) of the nuclear fraction was also quantified using western blotting. Catalase activity and glutathione content were determined by colorimetric assay kits. Nrf2 promoter‐luciferase activity was evaluated by a dual luciferase assay system.    Results  Treatment with tert‐butyl hydroperoxide decreased cell viability dose‐dependently.  DHA  or  EPA  pretreatment significantly alleviated tert‐butyl hydroperoxide‐induced cytotoxicity.  DHA  or  EPA  increased the messenger ribonucleic acid levels of Ho‐1, nicotinamide adenine dinucleotide (phosphate) H quinone oxidoreductase 1 and catalase dose‐dependently. Ho‐1 protein level, catalase activity, Nrf2 promoter‐luciferase activity and intracellular glutathione content were significantly increased by  DHA  and  EPA .    Conclusions  These findings show that  DHA  and  EPA  can induce Ho‐1 and catalase through Nrf2, thus protecting Schwann cells against oxidative stress. ω‐3  PUFA s appear to exert their neuroprotective effect by increasing defense mechanisms against oxidative stress in diabetic neuropathies.

journal of diabetes investigation

Omega‐3 polyunsaturated fatty acids exert anti‐oxidant effects through the nuclear factor (erythroid‐derived 2)‐related factor 2 pathway in immortalized mouse Schwann cells