期刊
KIDNEY INTERNATIONAL
卷 78, 期 9, 页码 905-919出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2010.265
关键词
albuminuria; diabetic nephropathy; NADPH oxidase; oxidative stress
资金
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan [16590888]
- Special Coordination Funds for Promoting Science and Technology (SCF)
- Grants-in-Aid for Scientific Research [16590888] Funding Source: KAKEN
We recently found a markedly lower prevalence of vascular complications, including kidney disease, in diabetic patients with Gilbert syndrome, a congenital form of hyperbilirubinemia, suggesting a beneficial effect of bilirubin (BIL) on diabetic nephropathy. To directly examine this, we determined whether hereditary hyperbilirubinemic Gunn j/j rats and biliverdin (BVD)-treated diabetic db/db mice were resistant to the development of renal disease. Both rodent models had less albuminuria and complete protection against the progression of mesangial expansion accompanied by normalization of transforming growth factor-beta 1 and fibronectin expression. Simultaneously, there was normalization of urinary and renal oxidative stress markers, and the expression of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits in the kidney. In cultured vascular endothelial and mesangial cells, BIL and BVD significantly inhibited NADPH-dependent superoxide production, and both high glucose-and angiotensin II-induced production of reactive oxygen species. Collectively, our findings suggest that BIL and BVD may protect against diabetic nephropathy and may lead to novel antioxidant therapies for diabetic nephropathy. Kidney International (2010) 78, 905-919; doi:10.1038/ki.2010.265;published online 4 August 2010
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