代谢
邻茴香胺的代谢和作用模式尚未完全阐明。看起来，与其他芳香胺一样，邻茴香胺被氧化成N-羟基衍生物，该衍生物与血红蛋白的血红素部分相互作用，导致高铁血红蛋白的形成。与其他芳香胺一样，N,O-乙酰化可能参与邻茴香胺的代谢激活。在含有高水平N-或O-乙酰转移酶活性的伤寒沙门氏菌菌株的细菌基因突变试验中，可以检测到邻茴香胺的致突变活性。体外研究表明，过氧化物酶如前列腺素H合酶可能在邻茴香胺的代谢激活中发挥作用。前列腺素H合酶在哺乳动物组织中广泛分布，包括膀胱。使用辣根过氧化物酶作为模型酶，描述了从邻茴香胺形成的反应中间体，这些中间体与核酸和蛋白质共价结合。形成的反应中间体包括亲电的二亚胺和醌亚胺代谢物。这些代谢物也由前列腺素H合酶形成。此外，邻茴香胺的代谢中可能发生O-脱甲基化。在一项使用大鼠肝微粒体的体外研究中，与从N,N-二甲基苯胺形成甲醛的速率相比，邻茴香胺的相对O-脱甲基化速率为13%。
The metabolism and mode of action of o-anisidine has not yet been fully elucidated. It seems, that like other aromatic amines, o-anisidine is oxidized to a N-hydroxy derivative, which interacts with the heme group of hemoglobin resulting in the formation of methemoglobin. As with other aromatic amines, N,O-acetylation may be involved in the metabolic activation of o-anisidine. In bacterial gene mutation assays with Salmonella typhimurium strains containing elevated levels of N- or O-acetyltransferase activity, mutagenic activity of o-anisidine could be detected. In vitro studies have suggested a possible role for peroxidation enzymes like prostaglandin H synthase in the metabolic activation of o-anisidine. Prostaglandin H synthase is broadly distributed in mammalian tissues including the urinary bladder. Using horseradish peroxidase as a model enzyme, the formation of reactive intermediates from o-anisidine, which were covalently bound to nucleic acids and protein, /was described/. The reactive intermediates formed included electrophilic diimine and quinoneimine metabolites. These metabolites were also formed with prostaglandin H synthase. Further, O-demethylation may occur in the metabolism of o-anisidine. In an in vitro study with microsomes from rat liver, the relative O-demethylation rate of o-anisidine as compared to the formation of formaldehyde from N,N-dimethylaniline was 13%.
来源:Hazardous Substances Data Bank (HSDB)
