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NDT Advance Access published online on April 20, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm166
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pyridoxal phosphate prevents progression of diabetic nephropathy

Sakurako Nakamura1, Hongyan Li1,2, Ayinuer Adijiang1, Monika Pischetsrieder3 and Toshimitsu Niwa1

1Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan, 2Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China and 3Institute of Pharmacy and Food Chemistry, University of Erlangen-Nürnberg, Erlangen, Germany

Correspondence and offprint requests to: Toshimitsu Niwa, Department of Clinical Preventive Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan. Email: tniwa{at}med.nagoya-u.ac.jp



  Abstract

Background. We have demonstrated that pyridoxal 5'-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 600 mg/kg/day for 16 weeks. AGEs [imidazolone, N{varepsilon}-(carboxymethyl)lysine (CML) and N2-carboxyethyl-2'-deoxyguanosine (CEdG)], transforming growth factor-ß1 (TGF-ß1), type 1 collagen and fibronectin were detected in the kidneys using immunohistochemistry. Gene expression of TGF-ß1 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-ß1, type 1 collagen, fibronectin and RAGE in the kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of TGF-ß1, 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.

Keywords: advanced glycation end-products (AGEs); diabetic nephropathy; pyridoxal 5'-phosphate (PLP); receptor for advanced glycation end-products (RAGE); transforming growth factor-ß1 (TGF-ß1)

Received for publication: 3. 6.06
Accepted in revised form: 5. 3.07


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