Abstract
Background Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant that is believed to protect the kidney through antioxidant action. However, the underlying mechanism of GSPE protection against DN remains unclear. Objective To explore if GSPE can improve DN by activating nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element signalling and to clarify its possible mechanism. Materials and methods. Ten healthy Sprague-Dawley rats were randomly selected as controls. Rats with streptozotocin-induced diabetes were randomly divided into three groups (10 animals/group): type 2 diabetes mellitus (T2DM) group (untreated), L-GSPE group (treated with 125-mg/kg/day GSPE for 8 weeks), and H-GSPE group (treated with 250 mg/kg/day GSPE for 8 weeks). Results Renal histopathological results indicated limited pathological damage in GSPE-treated groups. Compared with the T2DM group, the H-GSPE group had significantly reduced kidney weight and renal index. Similarly, the levels of fasting blood glucose, serum creatinine, blood urea nitrogen, uric acid, urinary albumin, and renal malondialdehyde (p < 0.05) were also significantly decreased. In addition, GSPE significantly increased the levels of superoxide dismutase, total antioxidative capability, and glutathione (p < 0.05) as well as the protein levels of Nrf2, HO-1, glutathione S-transferase, and NAD (P)H quinone oxidoreductase 1 (p < 0.05). Conclusion The results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf2 signalling pathway, which consequently increased the antioxidant capacity of the tissue. Therefore, GSPE is a potential natural agent for the treatment of diabetic nephropathy.
Highlights
Diabetes mellitus is a metabolic syndrome which results from inadequate insulin or impaired action of insulin
According to the report of the International Diabetes Federation [1], about 463 million adults suffer from diabetes globally in 2019. e increase in the incidence of diabetes has led to higher prevalence of complications such as Diabetic nephropathy (DN) [2], and approximately 20–40% of patients with diabetes develop DN [3]
Hyperglycaemia in diabetes can activate the polyol pathway, the hexosamine pathway, the protein kinase C pathway, advanced glycation end products, and the glyceraldehyde autoxidation pathway. ese pathways are possibly involved in the production of reactive oxygen species (ROS) and the development of oxidative stress, which are associated with the pathogenesis of diabetes and its complications [6]
Summary
Diabetes mellitus is a metabolic syndrome which results from inadequate insulin or impaired action of insulin. DN is the main cause of end-stage renal disease, accounting for approximately 50% of cases in the developed countries [4]. It is an independent risk factor for the development and progression of cardiovascular diseases [5], placing a heavy economic burden on healthcare systems globally. To explore if GSPE can improve DN by activating nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element signalling and to clarify its possible mechanism. E results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf signalling pathway, which increased the antioxidant capacity of the tissue. Conclusion. e results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf signalling pathway, which increased the antioxidant capacity of the tissue. erefore, GSPE is a potential natural agent for the treatment of diabetic nephropathy
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