Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase

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.

• Publication year

  2011

• Venue

  Journal of Biomedical Sciences

• Publication date

  2011-06-23

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/1423-0127-18-47PMID 21699681PMCID 3150248
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2009cited by this paper
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• Peroxynitrite plays a key role in glomerular lesions in diabetic rats.

  2009cited by this paper
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  2009cited by this paper
• Nutrient Stress Activates Inflammation and Reduces Glucose Metabolism by Suppressing AMP-Activated Protein Kinase in the Heart

  2009cited by this paper
• Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

  2009cited by this paper
• Berberine suppresses proinflammatory responses through AMPK activation in macrophages.

  2009cited by this paper
• Oxidative stress-induced JNK activation contributes to proinflammatory phenotype of aging diabetic mesangial cells.

  2009cited by this paper
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  2008cited by this paper
• Improvement of inflammatory responses associated with NF-κB pathway in kidneys from diabetic rats

  2008cited by this paper
• [Urinary excretion of proinflammatory cytokines and transforming growth factor beta at early stages of diabetic nephropathy].

  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2007cited by this paper
• Oxidative stress and cellular stress response in diabetic nephropathy

  2007cited by this paper
• A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy.

  2007cited by this paper
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  2002cited by this paper
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