Pterostilbene Prevents Early Diabetic Retinopathy Alterations in a Rabbit Experimental Model

Abstract

Oxidative stress generated by diabetes plays a key role in the development of diabetic retinopathy (DR), a common diabetic complication. DR remains asymptomatic until it reaches advanced stages, which complicate its treatment. Although it is known that good metabolic control is essential for preventing DR, knowledge of the disease is incomplete and an effective treatment with no side effects is lacking. Pterostilbene (Pter), a natural stilbene with good antioxidant activity, has proved to beneficially affect different pathologies, including diabetes. Therefore, our study aimed to analyse the protective and/or therapeutic capacity of Pter against oxidant damage by characterising early retinal alterations induced by hyperglycaemia, and its possible mechanism of action in a rabbit model of type 1 diabetes mellitus. Pter reduced lipid and protein oxidative damage, and recovered redox status and the main activities of antioxidant enzymes. Moreover, the redox regulation by Pter was associated with activation of the PI3K/AKT/GSK3β/NRF2 pathway. Our results show that Pter is a powerful protective agent that may delay early DR development.

Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene

“…It is well-known that chronic hyperglycemia is a potent inductor of reactive oxygen species. In a recent study, using the current experimental model, we showed that hyperglycemia induces very early lipid oxidation in retina tissue of diabetic animals [ 7 ]. In addition, our group showed the ability of Pter to lower lipid peroxidation evaluated by 4-hydroxy-2-nonenal levels in diabetic treated animals [ 7 ].…”

“…Polyphenols are the most abundant antioxidants in the human diet [ 31 ] and their beneficial effects have prompted interest in their use for treating retinal pathologies. For example, a protective effect has been observed against DR and other retinopathies with curcumin [ 32 , 33 ], resveratrol [ 34 , 35 , 36 ], quercetin [ 37 , 38 ], epigallocatechin gallate [ 39 , 40 ], and Pter [ 7 ], among others. The all have one thing in common, their antioxidant capacity against oxidative stress after hypoxia [ 41 , 42 ] and their significant ability to stop the pathological angiogenesis [ 43 ] by reducing levels of the vascular endothelial growth factor (VEGF) [ 44 ].…”

“…Recently, we showed for the first time that daily Pter administration at non-toxic and biologically effective doses of 50 mg/kg can prevent the early neuro-retinal damage caused by hyperglycemia in vivo [ 7 ]. It is known that retinal neural cell death appears in early stages of the development of DR, even prior to the appearance of the classic phenotypic characteristics used in its diagnosis [ 7 , 45 , 46 , 47 ].…”

“…Pterostilbene (Pter), a natural analog of resveratrol, has recently been proposed as an inhibitor of aldose reductase, the rate-limiting enzyme of the polyol pathway, and AGE production [ 8 ], besides, it was able to reduce the levels of hexose and hexosamine in plasma, hepatic, and renal tissues to control values in diabetic animals [ 9 ], showing the polyphenol as a possible therapeutic agent against long-term complications of diabetes. Our group showed that parenteral daily administration of Pter, trans-3,5-dimethoxy-4′-hydroxystilbene, protected alloxan-induced diabetic rabbits by attenuating hyperglycemia-mediated oxidative stress via PI3K/AKT/GSK3β/NRF2 pathway [ 7 ]. The stilbene reduced lipid and protein oxidative damage, stimulated the activity of superoxide dismutase, catalase and glutathione peroxidase and increased GSH levels in the retina with a reduction in oxidative stress preventing early DR alterations [ 7 ].…”

“…Our group showed that parenteral daily administration of Pter, trans-3,5-dimethoxy-4′-hydroxystilbene, protected alloxan-induced diabetic rabbits by attenuating hyperglycemia-mediated oxidative stress via PI3K/AKT/GSK3β/NRF2 pathway [ 7 ]. The stilbene reduced lipid and protein oxidative damage, stimulated the activity of superoxide dismutase, catalase and glutathione peroxidase and increased GSH levels in the retina with a reduction in oxidative stress preventing early DR alterations [ 7 ].…”