期刊
CLINICAL SCIENCE
卷 125, 期 7-8, 页码 361-382出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20130065
关键词
diabetes; diabetic complications; hyperglycaemia; oxidative stress; Nox; reactive oxygen species; small-molecule inhibitor
资金
- Juvenile Diabetes Research Foundation
- National Institutes of Health [RO1 DK 079996, RO1 CA 131272]
- Veterans Administration
Oxidative stress has been linked to the pathogenesis of the major complications of diabetes in the kidney, the heart, the eye or the vasculature. NADPH oxidases of the Nox family are a major source of ROS (reactive oxygen species) and are critical mediators of redox signalling in cells from different organs afflicted by the diabetic milieu. In the present review, we provide an overview of the current knowledge related to the understanding of the role of Nox in the processes that control cell injury induced by hyperglycaemia and other predominant factors enhanced in diabetes, including the renin angiotensin system, TGF-beta (transforming growth factor-beta) and AGEs (advanced glycation end-products). These observations support a critical role for Nox homologues in diabetic complications and indicate that NADPH oxidases are an important therapeutic target. Therefore the design and development of small-molecule inhibitors that selectively block Nox oxidases appears to be a reasonable approach to prevent or retard the complications of diabetes in target organs. The bioefficacy of these agents in experimental animal models is also discussed in the present review.
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