Aminoguanidine does not inhibit aldose reductase activity in galactose-fed rats.
Aminoguanidine, nucleophilic hydrazine derivative, has been shown to inhibit diamine oxidase, the formation of advanced glycation endproducts, nitric oxide synthase, and catalase. Prompted by the reports that aminoguanidine also inhibits aldose reductase (AR), we have investigated the effect of aminoguanidine, 1,3-diaminoguanidine, and methylguanidine on AR activity in vitro, and in vivo. In vitro, we have measured the inhibition of AR isolated from bovine lenses; in vivo, we have examined the effect on the galactitol levels in the red blood cells, sciatic nerve, retina, and lens of rats administered the test compounds for 11 days in the drinking water and, for the last 4 days, given access to a 20% galactose diet. Two known, structurally distinct AR inhibitors, tolrestat and compound WAY-121,509, were used as reference. In vitro, at concentrations up to 1.0 mmol/L, none of the tested guanidine derivatives had any effect on AR. As a corollary, in vivo, at doses ranging from 201 to 349 mg/kg/day, none of the guanidine derivatives affected tissular galactitol levels. We conclude that, in short-term galactose-fed rats, at the doses tested, aminoguanidine, 1,3-diaminoguanidine, and methylguanidine do not inhibit AR.
Dvornik
D
D
Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA.
Hohman
T C
TC
Basso
M D
MD
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000494:pharmacology; D000818:Animals; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005690:Galactose / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008760:Methylguanidine / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D009281:Naphthalenes; C091470:WAY 121-509; C040550:tolrestat; C070130:diaminoguanidine; D008760:Methylguanidine; D000449:Aldehyde Reductase; C004479:pimagedine; D005690:Galactose