In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.
Aminoguanidine (AG) is considered to be a promising compound for the treatment of diabetic complications. We examined the in vitro and in vivo formation of Schiff bases of AG with pyridoxal 5'-phosphate (PLP) and pyridoxal (PL). AG reacted in vitro far more rapidly with PLP to form a Schiff base (PLP-AG) than with PL to form another Schiff base (PL-AG). Administration of AG at 7 mM in drinking water for 18 weeks caused the formation of PLP-AG in the liver and kidney of mice (12.1 +/- 1.6 and 3.8 +/- 0.64 nmol/g of tissue, respectively, mean +/- SD, N = 6). The amount of PLP in the liver of mice AG administered was significantly lower than that of control mice (4.0 +/- 1.4 vs 17.4 +/- 1.3 nmol/g of wet tissue, mean +/- SD, N = 6). Simultaneous administration of pyridoxine (1 mM in drinking water) with AG (7 mM in drinking water) did not ameliorate the decrease in tissue PLP and caused the excess formation of PLP-AG. The results suggest that attention should be paid to the deficiency of tissue PLP in the clinical use of AG.
Taguchi
T
T
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Sugiura
M
M
Hamada
Y
Y
Miwa
I
I
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006146:Guanidines / Q000008:administration & dosage / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D051379:Mice; D011732:Pyridoxal Phosphate / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry*
D006146:Guanidines; D012545:Schiff Bases; D011732:Pyridoxal Phosphate; C004479:pimagedine