(14-02-11) Resveratrol Improves Oxidative Stress and Protects Against Diabetic Nephropathy Through Normalization of Mn-SOD Dysfunction in AMPK/

Resveratrol Improves Oxidative Stress and Protects Against Diabetic Nephropathy Through Normalization of Mn-SOD Dysfunction in AMPK/SIRT1-Independent Pathway.
Kitada M, Kume S, Imaizumi N, Koya D.

Corresponding author: Daisuke Koya, [email protected].
Abstract
OBJECTIVE Despite the beneficial effects of resveratrol (RSV) on
cardiovascular disease and life span, its effects on type 2 diabetic
nephropathy remain unknown. This study examined the renoprotective effects of
RSV in db/db mice, a model of type 2 diabetes. RESEARCH DESIGN AND METHODS
db/db mice were treated with RSV (0.3% mixed in chow) for 8 weeks. We measured
urinary albumin excretion (UAE), histological changes (including mesangial
expansion, fibronectin accumulation, and macrophage infiltration), oxidative
stress markers (urinary excretion and mitochondrial content of 8-hydroxy-2'-
deoxyguanosine [8-OHdG], nitrotyrosine expression), and manganese-superoxide
dismutase (Mn-SOD) activity together with its tyrosine-nitrated modification
and mitochondrial biogenesis in the kidney. Blood glucose, glycated hemoglobin,
and plasma lipid profiles were also measured. The phosphorylation of 5'-AMP-
activated kinase (AMPK) and expression of silent information regulator 1
(SIRT1) in the kidney were assessed by immunoblotting. RESULTS RSV
significantly reduced UAE and attenuated renal pathological changes in db/db
mice. Mitochondrial oxidative stress and biogenesis were enhanced in db/db
mice; however, Mn-SOD activity was reduced through increased tyrosine-nitrated
modification. RSV ameliorated such alterations and partially improved blood
glucose, glycated hemoglobin, and abnormal lipid profile in db/db mice.
Activation of AMPK was decreased in the kidney of db/db mice compared with db/m
mice. RSV neither modified AMPK activation nor SIRT1 expression in the kidney.
CONCLUSIONS RSV ameliorates renal injury and enhanced mitochondrial biogenesis
with Mn-SOD dysfunction in the kidney of db/db mice, through improvement of
oxidative stress via normalization of Mn-SOD function and glucose-lipid
metabolism. RSV has antioxidative activities via AMPK/SIRT1-independent pathway.

Source: Diabetes. 2011 Feb;60(2):634-43.

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