| Summary: | <p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn<sup>2+</sup> is essential for the activity of Δ<sup>6</sup> desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.</p> <p>Methods</p> <p>RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn<sup>2+</sup>. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated.</p> <p>Results</p> <p>Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and α-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn<sup>2+</sup> and ALA. ALA was more potent that Zn<sup>2+</sup>. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells.</p> <p>Conclusions</p> <p>These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.</p>
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