Evidence for in vivo scavenging by aminoguanidine of formaldehyde produced via semicarbazide-sensitive amine oxidase-mediated deamination.
Aminoguanidine (AG) is capable of preventing advanced protein glycation and inhibiting the activity of enzymes with carbonyl groups as cofactors, such as nitric-oxide synthase (NOS) and semicarbazide-sensitive amine oxidase (SSAO). The hydrazide moiety of AG can also interact with different endogenous carbonyl metabolites and potentially harmful endogenous aldehydes. Aldehydes can be generated via different pathways, such as lipid peroxidation (malondialdehyde and 4-hydroxynonenal), oxidative deamination (aldehydes), and carbohydrate metabolism (methylglyoxal). Formaldehyde and methylglyoxal are produced via SSAO-catalyzed deamination of methylamine and aminoacetone, respectively. An increase in SSAO-mediated deamination is known to be associated with various vascular disorders, such as diabetic complications. The present study demonstrates that AG is not only capable of rapidly interacting with aldehydes in vitro but also scavenging aldehydes in vivo. The AG-formaldehyde adducts were traced, and their structures were elucidated by high-performance liquid chromatography-mass spectrometry. AG has also been shown to block formaldehyde-induced beta-amyloid aggregation. Thus, AG can be an aldehyde scavenger in addition to blocking advanced glycation and inhibition of SSAO and NOS activity. Such reactions may contribute to its pharmacological effects in the treatment of vascular disorders associated with diabetic complications and other disorders.
Kazachkov
Michael
M
Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E4, Canada.
Chen
Kun
K
Babiy
Sergey
S
Yu
Peter H
PH
D000447:Aldehydes / Q000378:metabolism; D000586:Amination; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003925:Diabetic Angiopathies; D005557:Formaldehyde / Q000378:metabolism*; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
D000447:Aldehydes; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D006146:Guanidines; D005557:Formaldehyde; D019001:Nitric Oxide Synthase; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine