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Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells.

Shen J, Shen S, Das UN, Xu G - Lipids Health Dis (2012)

Bottom Line: Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity.These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Clinical Visual Science, Tongji Eye institute, Tongji University School of Medicine, Shanghai, China.

ABSTRACT

Background: 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. Zn2+ is essential for the activity of Δ6 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.

Methods: RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. 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.

Results: 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 Zn2+ and ALA. ALA was more potent that Zn2+. 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.

Conclusions: These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

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Effect of various concentrations of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity. Data are mean ± S.D. Different superscript letters indicate significantly different means.
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Figure 3: Effect of various concentrations of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity. Data are mean ± S.D. Different superscript letters indicate significantly different means.

Mentions: High glucose is known to be cytotoxic, partly by inducing mitochondrial stress [16,17]. Hence, we studied the effect of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity as a marker of mitochondrial stress. A dose–response study showed that the activity of the enzyme was suppressed at all the concentrations of glucose (5, 15, 25 mM) significantly (Figure 3). With 25 mM glucose incubation for short time (48 hours), the activity decreased by 36.94%. Although ALA alone inhibited the activity of the enzyme by ~10- ~ 20%, it appeared to ameliorate glucose-induced suppression of succinate dehydrogenase activity by 25% (200 μM ALA co-treatment with 25 mM glucose).


Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells.

Shen J, Shen S, Das UN, Xu G - Lipids Health Dis (2012)

Effect of various concentrations of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity. Data are mean ± S.D. Different superscript letters indicate significantly different means.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475048&req=5

Figure 3: Effect of various concentrations of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity. Data are mean ± S.D. Different superscript letters indicate significantly different means.
Mentions: High glucose is known to be cytotoxic, partly by inducing mitochondrial stress [16,17]. Hence, we studied the effect of ALA on glucose-induced changes in mitochondrial succinate dehydrogenase enzyme activity as a marker of mitochondrial stress. A dose–response study showed that the activity of the enzyme was suppressed at all the concentrations of glucose (5, 15, 25 mM) significantly (Figure 3). With 25 mM glucose incubation for short time (48 hours), the activity decreased by 36.94%. Although ALA alone inhibited the activity of the enzyme by ~10- ~ 20%, it appeared to ameliorate glucose-induced suppression of succinate dehydrogenase activity by 25% (200 μM ALA co-treatment with 25 mM glucose).

Bottom Line: Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity.These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Clinical Visual Science, Tongji Eye institute, Tongji University School of Medicine, Shanghai, China.

ABSTRACT

Background: 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. Zn2+ is essential for the activity of Δ6 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.

Methods: RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. 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.

Results: 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 Zn2+ and ALA. ALA was more potent that Zn2+. 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.

Conclusions: These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

Show MeSH
Related in: MedlinePlus