Combined AGE inhibition and ACEi decreases the progression of established diabetic nephropathy in B6 db/db mice
Kidney International. 2006-08-01; 70(3): 507-514
DOI: 10.1038/sj.ki.5001578
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1. Kidney Int. 2006 Aug;70(3):507-14. doi: 10.1038/sj.ki.5001578. Epub 2006 Jun
14.
Combined AGE inhibition and ACEi decreases the progression of established
diabetic nephropathy in B6 db/db mice.
Zheng F(1), Zeng YJ, Plati AR, Elliot SJ, Berho M, Potier M, Striker LJ, Striker
GE.
Author information:
(1)Department of Medicine, Vascular Biology Institute, University of Miami
School of Medicine, Miami, Florida, USA.
The accumulation of advanced glycation end products (AGE) is a key factor in
diabetic nephropathy (DN). Pyridoxamine inhibits AGE formation and protects
against type I DN. Herein we tested: (1) whether C57BL6 db/db mice as a model of
established type II DN resembled patients treated with drugs which inhibit
angiotensin II action; (2) whether pyridoxamine was effective as a single
therapy; and (3) whether pyridoxamine would add to the benefit of
angiotensin-converting enzyme inhibition (ACEi) by enalapril. In first set of
experiments mice were treated with ACEi (benazepril) and an angiotensin II
receptor blocker (valsartan) combination for 16 weeks after the onset of
diabetes. In second group, mice with established DN were treated with
pyridoxamine for 8 weeks. In a third set, mice with established DN were treated
with pyridoxamine and enalapril combination for 16 weeks. Benazepril and
valsartan combination partially prevented the development and progression of DN.
Pyridoxamine treatment, as single therapy, decreased the progression of
albuminuria and glomerular lesions. The combination of pyridoxamine with
enalapril reduced both mortality and the progression of DN. In conclusion, (1)
C57 BL6 db/db mice are a model of progressive type II DN; (2) The combination of
pyridoxamine with enalapril decreased progression of type 2 DN and overall
mortality. Thus, pyridoxamine could be a valuable adjunct to the current
treatment of established type II DN.
DOI: 10.1038/sj.ki.5001578
PMID: 16775596 [Indexed for MEDLINE]