Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice.
Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct. Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct significantly improved urinary albumin excretion by 78.1 % compared with the diabetic control, and also had a better preventive effect on the progression of renal pathology than aminoguanidine did. Inhibition of glycation by both drugs was similar, but the antioxidant activity of the pyridoxal adduct was far superior. These findings suggest that aminoguanidine pyridoxal adduct may be superior to aminoguanidine, as it not only prevents vitamin B6 deficiency but is also better at controlling diabetic nephropathy, as this adduct inhibits oxidation as well as glycation.
Miyoshi
H
H
Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Taguchi
T
T
Sugiura
M
M
Takeuchi
M
M
Yanagisawa
K
K
Watanabe
Y
Y
Miwa
I
I
Makita
Z
Z
Koike
T
T
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000473:pathology / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006900:Hydroxylation; D007202:Indicators and Reagents; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016707:Tissue Fixation; D014563:Urodynamics / Q000187:drug effects; D015034:Zinc Oxide / Q000737:chemistry
D001391:Azo Compounds; D001565:Benzoates; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007202:Indicators and Reagents; D016877:Oxidants; C471830:aminoguanidine pyridoxal adduct; D011730:Pyridoxal; C100258:methyl orange; D006861:Hydrogen Peroxide; C004479:pimagedine; D015034:Zinc Oxide