Kazachkov Michael, Chen Kun, Babiy Sergey, Yu Peter H
Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E4, Canada.
J Pharmacol Exp Ther. 2007 Sep;322(3):1201-7. doi: 10.1124/jpet.107.124123. Epub 2007 Jun 27.
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.
氨基胍（AG）能够预防晚期蛋白质糖基化，并抑制以羰基为辅因子的酶的活性，如一氧化氮合酶（NOS）和氨基脲敏感胺氧化酶（SSAO）。AG的酰肼部分还可以与不同的内源性羰基代谢产物和潜在有害的内源性醛相互作用。醛可通过不同途径产生，如脂质过氧化（丙二醛和4-羟基壬烯醛）、氧化脱氨（醛类）和碳水化合物代谢（甲基乙二醛）。甲醛和甲基乙二醛分别通过SSAO催化的甲胺和氨基丙酮脱氨产生。已知SSAO介导的脱氨增加与各种血管疾病有关，如糖尿病并发症。本研究表明，AG不仅能够在体外与醛快速相互作用，还能在体内清除醛。追踪了AG-甲醛加合物，并通过高效液相色谱-质谱法阐明了它们的结构。AG还被证明能阻止甲醛诱导的β-淀粉样蛋白聚集。因此，AG除了能阻止晚期糖基化以及抑制SSAO和NOS活性外，还可以作为醛清除剂。此类反应可能有助于其在治疗与糖尿病并发症及其他疾病相关的血管疾病中的药理作用。
