In this study, we identified the binding sites and structurally characterized the interaction between gigantol and AR, to understand the mechanism (s) of the effects of gigantol on cataracts.
Aldose reductase (AR) is an NADPH-dependent aldo-keto reductase that has been shown to be involved in the pathogenesis of several blinding diseases such as uveitis, diabetic retinopathy (DR) and cataract.
The results suggest that the protective effect of TXF against cataract and retinopathy may be due to the anti-oxidative potential of TXF and its inhibiting effect on VEGF, ERK1/2, p38MAPK and aldose reductase.
Methanol extract of H. indicus-inhibited AR activity in vitro decreased the blood glucose levels, inhibited the AR activity and delayed the onset and progression of cataract in a dose-dependent manner in in vivo and the antioxidant markers have been normalised.
Protective effect of <i>Pterocarpus marsupium</i> bark extracts against cataract through the inhibition of aldose reductase activity in streptozotocin-induced diabetic male albino rats.
Lens opacity was evaluated every week throughout a study period whereas the evaluation of cataract severity and histological changes of both rat lens epithelium and retina together with the biochemical assays of oxidative stress status, aldose reductase, p38MAPK, ERK1/2, and VEGF were performed at the end of experiment.
In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress.
At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats.
We observed that nondiabetic AR-TG mice did not show lens structural changes even though they had lenticular sorbitol levels almost as high as the diabetic AR-TG lenses that showed early signs of cataract.
We observed that nondiabetic AR-TG mice did not show lens structural changes even though they had lenticular sorbitol levels almost as high as the diabetic AR-TG lenses that showed early signs of cataract.
In type 2 diabetic patients with suboptimal glycaemic control, the z-4 allele of ALR2 (CA)n polymorphism was independently associated with increased susceptibility to cataracts.
To elucidate a potential role for this enzyme in diabetic cataract formation, we created a series of transgenic mice designed for expression of human ALR2 (AKR1B1) in epithelial and outer cortical fiber cells of the lens.
Studies with transgenic mice that over-express AKR1B1 indicate that it is the key protein for the development of diabetic complications including diabetic cataract.
In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.
However, the introduction of a human aldose reductase transgene into a GK-deficient background resulted in cataract formation within the first postnatal day.
To settle this issue we developed transgenic mice that overexpress AR in their lens epithelial cells and found that they become susceptible to the development of diabetic and galactose cataracts.