Hesperidin Prevents Retinal and Plasma Abnormalities in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetic retinopathy is a complex disease that potentially involves increased production of advanced glycosylation end products (AGEs) and elevated aldose reductase (AR) activity, which are related with oxidative stress and inflammation. The aim of this study was to investigate the effects of hesperidin on retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Hesperidin (100, 200 mg/kg daily) was given to diabetic rats for 12 weeks. The blood-retina breakdown (BRB) was determined after 2 weeks of treatment followed by the measurement of related physiological parameters with ELISA kits and immunohistochemistry staining at the end of the study. Elevated AR activity and blood glucose, increased retinal levels of vascular endothelial growth factor (VEGF), ICAM-1, TNF-α, IL-1β and AGEs as well as reduced retina thickness were observed in diabetic rats. Hesperidin treatment significantly suppressed BRB breakdown and increased retina thickness, reduced blood glucose, AR activity and retinal TNF-α, ICAM-1, VEGF, IL-1β and AGEs levels. Furthermore, treatment with hesperidin significantly reduced plasma malondialdehyde (MDA) levels and increased SOD activity in diabetic rats. These data demonstrated that hesperidin attenuates retina and plasma abnormalities via anti-angiogenic, anti-inflammatory and antioxidative effects, as well as the inhibitory effect on polyol pathway and AGEs accumulation.

Influence of flavonoid-rich fruit and vegetable intake on diabetic retinopathy and diabetes-related biomarkers

“…Not only was HFVC an independent predictor of diabetes-related biomarkers, but for each 10 U increase in HFVC index, participants had 33% lower odds to have retinopathy. This significant finding is supported in the literature via animal and in vitro work (Kim et al, 2012;Kumar et al, 2013;Shi et al, 2012). Importantly, our work, unlike these previous animal-related studies, demonstrates that flavonoid consumption achieved through normal fruit and vegetable intake, rather than supplementation, is associated with diabetesrelated biomarkers and diabetic retinopathy.…”

Diabetes enhances the efficacy of AAV2 vectors in the retina: therapeutic effect of AAV2 encoding vasoinhibin and soluble VEGF receptor 1

“…When evaluated using the retinal accumulation of Evans blue or other plasma tracers, BRBB was reported as early as 5 days and up to 10 weeks post-STZ treatment. 3,4,9,[11][12][13][14] Here, we confirmed the early and sustained damage of the BRB in this diabetes model by showing that a significant increase in the retinal accumulation of Evans blue-stained albumin occurs at 2 weeks AAV2 vectors reverse diabetic retinal alterations N Díaz-Lezama et al after STZ injection and is maintained at a similar level during the following 4 and 6 weeks (Figure 2a). To investigate the restoration of the BRB function, vehicle or 2.8 × 10 9 vg of the AAV2 vasoinhibin vector or the AAV2 sFlt-1 vector was injected intravitreally into non-diabetic or diabetic rats 2 weeks after treatment with STZ, and the BRBB was quantified 4 weeks after vector administration by the retinal accumulation of Evans blue.…”

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

“…The concept of ICAM-1 inhibition has become a potential therapeutic strategy for the prevention of diabetic retinopathy (Joussen et al, 2001;Miyamoto et al, 1999). Some flavonoid compounds, such as hesperidin, trans-chalcone, and minocycline, were reported to possess properties to inhibit diabetic-induced (Lamoke et al, 2011) or ischemia-induced (Abcouwer et al, 2013;Shi et al, 2012) ICAM-1 expression in retina. Our immunofluorescence and Western blot analysis also clearly supported that silybin effectively inhibited the up-regulated ICAM-1 protein (Fig.…”