Pyridoxal phosphate prevents progression of diabetic nephropathy.
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(epsilon)-(carboxymethyl)lysine (CML) and N(2)-carboxyethyl-2'-deoxyguanosine (CEdG)], transforming growth factor-beta1 (TGF-beta1), type 1 collagen and fibronectin were detected in the kidneys using immunohistochemistry. Gene expression of TGF-beta1 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-beta1, type 1 collagen, fibronectin and RAGE in the kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of TGF-beta1, 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.
Nakamura
Sakurako
S
Department of Clinical Preventive Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
Li
Hongyan
H
Adijiang
Ayinuer
A
Pischetsrieder
Monika
M
Niwa
Toshimitsu
T
D000284:Administration, Oral; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D017127:Glycation End Products, Advanced; D007668:Kidney / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D011733:Pyridoxamine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D025101:Vitamin B 6 / Q000378:metabolism
D005353:Fibronectins; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D053773:Transforming Growth Factor beta1; D011732:Pyridoxal Phosphate; D013311:Streptozocin; D011733:Pyridoxamine; D025101:Vitamin B 6