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Hesperetin Protects Diabetic Retinopathy Through Its Antioxidant, Anti-inflammatory And Anti-Angiogenic Pathways In Streptozotocin (STZ)-Induced Diabetic Rats 1. SK Gupta¹ ¹Delhi Institute of Pharmaceutical Sciences & Research, New Delhi, India Purpose: Objective of this study was to evaluate effect of Hesperetin, a plant based flavanone, on diabetes-induced retinal oxidative stress, inflammation and angiogenesis in rats for the prevention of diabetic retinopathy. Methods: Hesperetin treatment @100mg/kg b.wt. was carried out for 6months in STZ-induced diabetic rats. Hypoglycemic, antioxidant, inflammatory (TNF-α, IL-1β) and angiogenesis parameters (VEGF, PKC-β) were evaluated. Retinal changes were observed every month by funduscopy. Histopathology of retina was done at the termination of experiment. Results: Retinal glutathione levels were 3.76±0.62 and 9.20±0.98µmole/mg protein in diabetic and hesperetin-treated rats respectively. Retinal superoxide dismutase and catalase levels of diabetic rats were 2.03±0.24 & 3.01±0.41 IU/mg protein respectively which were restored to 5.18±0.60 & 9.25±0.54 IU/mg protein in hesperetin-treated rats. TNF- α and IL-1β expressions of 42.24±4.48 & 93.49±8.10 pg/mg protein of diabetic group were significantly increased in comparison to 25.25±2.13 & 62.79±6.16 of hesperetin-treated group. Levels of angiogenesis mediators VEGF and PKC-β were 19.80±1.31 & 144.22±12.89 mg/pg protein respectively in diabetic group which were significantly reduced to 12.58±1.22 & 74.00±10.98 mg/pg protein in hesperetin-treated group. Thickened retinal vascular basement membrane was seen in diabetic rats in comparison to normal and hesperetin-treated group. Conclusion: The beneficial effects of hesperetin in rescuing the retinal oxidative stress and inhibition of over-expression of pro-inflammatory and angiogenesis mediators in the development of experimental diabetic retinopathy suggests its potential role in the prevention and treatment of diabetic retinopathy in humans. |
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