Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of different concentrations of fatty acids on the proliferation of RF/6A cells in the presence of 10 mM glucose.(A)Linoleic acid (B) α-Linolenic acid (C) palmitic acid. *P < 0.05 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475048&req=5

Figure 2: Effect of different concentrations of fatty acids on the proliferation of RF/6A cells in the presence of 10 mM glucose.(A)Linoleic acid (B) α-Linolenic acid (C) palmitic acid. *P < 0.05 compared to control.

Mentions: Next the effect of EFAs: linoleic acid (LA) and α-linolenic acid (ALA) on the proliferation of RF/6A cells in the presence of varying concentrations of glucose was tested. It can be seen from Figure 2 that both LA and ALA significantly ameliorated glucose induced proliferation of cells to near normal, while saturated fatty acid: palmitic acid was ineffective. It is interesting to note that LA by itself enhanced while ALA suppressed the growth of RF/6A cells (Figure 2A and 2B). On the other hand, palmitic acid enhanced the growth of RF/6A cells though it was not statistically significant (Figure 2C). This suggests that possibly, only unsaturated fatty acids are capable of influencing enhanced proliferation induced by glucose. It is also likely that glucose and EFAs interact with each other to produce a metabolite of either glucose or EFAs or both (glucose and EFAs) that, in turn, suppresses the growth of RF/6A cells in vitro.


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 different concentrations of fatty acids on the proliferation of RF/6A cells in the presence of 10 mM glucose.(A)Linoleic acid (B) α-Linolenic acid (C) palmitic acid. *P < 0.05 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of different concentrations of fatty acids on the proliferation of RF/6A cells in the presence of 10 mM glucose.(A)Linoleic acid (B) α-Linolenic acid (C) palmitic acid. *P < 0.05 compared to control.
Mentions: Next the effect of EFAs: linoleic acid (LA) and α-linolenic acid (ALA) on the proliferation of RF/6A cells in the presence of varying concentrations of glucose was tested. It can be seen from Figure 2 that both LA and ALA significantly ameliorated glucose induced proliferation of cells to near normal, while saturated fatty acid: palmitic acid was ineffective. It is interesting to note that LA by itself enhanced while ALA suppressed the growth of RF/6A cells (Figure 2A and 2B). On the other hand, palmitic acid enhanced the growth of RF/6A cells though it was not statistically significant (Figure 2C). This suggests that possibly, only unsaturated fatty acids are capable of influencing enhanced proliferation induced by glucose. It is also likely that glucose and EFAs interact with each other to produce a metabolite of either glucose or EFAs or both (glucose and EFAs) that, in turn, suppresses the growth of RF/6A cells in vitro.

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