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- Title
Pyridoxal phosphate prevents progression of diabetic nephropathy.
- Authors
Sakurako Nakamura; Hongyan Li; Ayinuer Adijiang; Monika Pischetsrieder; Toshimitsu Niwa
- Abstract
Background. We have demonstrated that pyridoxal 5â²-phosphate (PLP), an active form of vitamin B6, inhibits formation of advanced glycation end-products (AGEs) by trapping 3-deoxyglucosone. The present study aimed to clarify if PLP could exert beneficial effects on nephropathy in diabetic rats. Methods. Streptozotocin (STZ)-induced diabetic rats were treated by oral administration of PLP or pyridoxamine (PM), another active form of vitamin B6, at a dose of 600âmg/kg/day for 16 weeks. AGEs [imidazolone, Nε-(carboxymethyl)lysine (CML) and N2-carboxyethyl-2â²-deoxyguanosine (CEdG)], transforming growth factor-β1 (TGF-β1), type 1 collagen and fibronectin were detected in the kidneys using immunohistochemistry. Gene expression of TGF-β1 and receptor for AGEs (RAGEs) in the kidneys was determined using real-time quantitative polymerase chain reaction. Results. Administration of PLP significantly inhibited albuminuria, glomerular hypertrophy, mesangial expansion, and interstitial fibrosis as compared with diabetic rats. PLP markedly inhibited accumulation of AGEs such as imidazolone, CML and CEdG, a DNA-linked AGE, in glomeruli. PLP significantly inhibited expression of TGF-β1, type 1 collagen, fibronectin and RAGE in the kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of TGF-β1, type 1 collagen, and fibronectin, and the development of diabetic nephropathy. Conclusions. PLP prevented progression of nephropathy in STZ-induced diabetic rats by inhibiting formation of AGEs. PLP is considered a promising active form of vitamin B6 for the treatment of AGE-linked disorders such as diabetic nephropathy.
- Subjects
VITAMIN B6; COENZYMES; DIABETIC nephropathies; DIABETES complications
- Publication
Nephrology Dialysis Transplantation, 2007, Vol 22, Issue 8, p2165
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfm166