Abstract
BackgroundDiabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN.MethodsThe protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats.ResultsThe plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys.ConclusionsOur findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.
Highlights
Diabetes mellitus (DM), mainly characterized by recurrent hyperglycemia, had become one of the chronic disorders derived from insulin deficiency or resistance in the developed countries
Our results show the renoprotective effects of RSV may contribute by its antioxidative and AMPK-up-regulating abilities and, to our interest, found that RSV significantly augmented inflammatory response in diabetic kidney by elevating several cytokines like tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6), despite its ameliorative effect on IL-1b cytokine level in Diabetic nephropathy (DN)
Effects of RSV on the body weight and biochemical parameters of the STZ-DM rats As shown in Table 1, blood glucose level was significantly higher in STZ-induced type 1 diabetic rats than in the normal controls
Summary
Diabetes mellitus (DM), mainly characterized by recurrent hyperglycemia, had become one of the chronic disorders derived from insulin deficiency or resistance in the developed countries. Diabetic nephropathy (DN), the second most both oxidative stress [5,6,7,8] and proinflammatory cytokines [9,10] detrimentally accelerated the pathological process of DN. Further studies indicated that suppression of AMPK activity was linked with oxidative stress [12] and inflammatory response [13]. Reversion of AMPK activity could ameliorate oxidative damage [14] and inflammation [15]. Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes.
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