Docampo R, Moreno S N
Rockefeller University, New York, New York.
Drug Metab Rev. 1990;22(2-3):161-78. doi: 10.3109/03602539009041083.
Gentian violet has been used in medicine for almost 100 years: as an antiseptic for external use, as an antihelminthic agent by oral administration, and more recently, as a blood additive to prevent transmission of Chagas' disease. To date, no serious side effects have been reported when used externally. However, oral administration can cause gastrointestinal irritation, and intravenous injection can cause depression in the white blood cell count. Surprisingly, no acute toxic side effects were reported after administration of large amounts of gentian violet-treated blood. No studies have been done on long-term effects (chronic toxicity, carcinogenicity) of gentian violet-treated blood either in humans or in laboratory animals. Gentian violet is a mutagen, a mitotic poison, and a clastogen. The carcinogenic effects of gentian violet in rodents have been reported recently. In addition, a number of triphenylmethane-classed dyes, of which gentian violet is a member, have been recognized as animal and human carcinogens. A photodynamic action of gentian violet, apparently mediated by a free-radical mechanism, has been described in bacteria and in T. cruzi. However, the main target of gentian violet toxicity in the dark is the mitochondrion. Gentian violet is actively demethylated by liver microsomes from different animals and is reduced to leucogentian violet by intestinal microflora. Although the first process may represent a detoxication reaction, the second pathway may have toxicological significance because the completely demethylated derivative leucopararosaniline has been demonstrated to be carcinogenic in rats. A free-radical derivative of gentian violet is also formed by the action of rat liver microsomes, but whether this radical is involved in the cytotoxic effects of gentian violet in mammalian cells remains to be elucidated. Other pathways of gentian violet metabolism have recently been investigated that involve its oxidative N-demethylation by peroxidases. The N-demethylation of gentian violet by prostaglandin synthetase deserves further study. In this regard, the PGS system is being studied as an alternative activating pathway in xenobiotic metabolism because some carcinogenic intermediates can be formed during this cooxidation reaction.
龙胆紫已在医学中使用了近100年：外用作为防腐剂，口服作为抗蠕虫药，最近还作为血液添加剂用于预防恰加斯病的传播。迄今为止，外用时未报告严重的副作用。然而，口服可引起胃肠道刺激，静脉注射可导致白细胞计数降低。令人惊讶的是，大量输注经龙胆紫处理的血液后未报告急性毒性副作用。尚未对经龙胆紫处理的血液在人类或实验动物中的长期影响（慢性毒性、致癌性）进行研究。龙胆紫是一种诱变剂、有丝分裂毒物和断裂剂。最近有报道称龙胆紫对啮齿动物有致癌作用。此外，包括龙胆紫在内的一些三苯甲烷类染料已被确认为动物和人类致癌物。在细菌和克氏锥虫中已描述了龙胆紫的光动力作用，显然是由自由基机制介导的。然而，龙胆紫在黑暗中产生毒性的主要靶点是线粒体。龙胆紫可被不同动物的肝脏微粒体积极去甲基化，并被肠道微生物群还原为无色龙胆紫。虽然第一个过程可能代表解毒反应，但第二个途径可能具有毒理学意义，因为完全去甲基化的衍生物无色副品红已被证明对大鼠有致癌性。大鼠肝脏微粒体的作用也会形成龙胆紫的自由基衍生物，但这种自由基是否参与龙胆紫对哺乳动物细胞的细胞毒性作用仍有待阐明。最近研究了龙胆紫代谢的其他途径，包括过氧化物酶对其进行氧化N-去甲基化。前列腺素合成酶对龙胆紫的N-去甲基化值得进一步研究。在这方面，前列腺素合成酶系统正作为外源性物质代谢中的一种替代激活途径进行研究，因为在这种共氧化反应过程中可能会形成一些致癌中间体。
