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Drug Metab Rev. 1990;22(2-3):161-78.

The metabolism and mode of action of gentian violet.

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Rockefeller University, New York, New York.


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.

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