Reduction of malachite green to leucomalachite green by intestinal bacteria

Henderson, Allison; Schmitt, Thomas; Heinze, Thomas M.; Cerniglia, Carl E.

doi:10.1128/aem.63.10.4099-4101.1997

Cited by 89 publications

(41 citation statements)

References 18 publications

(14 reference statements)

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“…The main biotransformation reactions undergone by MG are reductive and oxidative in nature. Reduction of MG yields the colourless derivative LMG (Figure 1 (Singh et al, 1994;Henderson et al, 1997); the role played by the gills in MG absorption and the extent of conversion of MG to LMG (see below) indicate that MG reduction to LMG could also occur in tissues, at least in piscine species. In treated fish, MG is rapidly cleared from the body while LMG is the predominant form in edible tissues where it may accumulate and persist for a long time due to a very slow excretion rate (Plakas et al, 1996;Alborali et al, 1997;Jiang et al, 2009).…”

Section: Toxicokineticsmentioning

confidence: 99%

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Malachite green in food

2016

EFS2

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Malachite green (MG) has been used globally in aquaculture but is not registered for use in food-producing animals in the European Union. The European Commission requested EFSA to evaluate whether a reference point for action (RPA) of 2 lg/kg for the sum of MG and its major metabolite leucomalachite green (LMG) is adequate to protect public health. Available occurrence data were not suitable for a reliable exposure assessment. The hypothetical dietary exposure was calculated, considering the RPA as occurrence value for all types of fish, fish products and crustaceans. Mean dietary exposure across different European dietary surveys and age classes would range from 0.1 to 5.0 ng/kg body weight (bw) per day. For high and frequent fish consumers, the exposure would range from 1.3 to 11.8 ng/kg bw per day. Both MG and LMG induced formation of DNA adducts in livers of rats and/or mice, and of micronuclei in mice. LMG also induced cII transgene mutations in mouse liver. MG caused a small, not dose-related, increase in thyroid gland follicular adenomas and carcinomas, and of mammary gland carcinomas in female rats. LMG caused an increase in hepatocellular adenomas and carcinomas in female mice. Both MG and LMG may be considered as carcinogenic and as genotoxic in vivo. A lower 95% confidence limit for a benchmark response of 10% extra risk (BMDL 10 ) of 13 mg/kg bw per day for hepatocellular adenomas and carcinomas was selected as reference point for neoplastic effects. For non-neoplastic effects, a lower 95% confidence limit for a benchmark response of 5% extra risk (BMDL 05 ) of 6 mg/kg bw per day was selected for the effect of MG on liver weight and of LMG on body weight. The margins of exposure were 1.1 9 10 6 or greater for neoplastic effects and 4.9 9 10 5 or greater for non-neoplastic effects. The CONTAM Panel concluded that it is unlikely that exposure to food contaminated with MG/LMG at or below the RPA of 2 lg/kg represents a health concern.Acknowledgements: The Panel wishes to thank the members of the Standing Working Group on non-allowed pharmacologically active substances in food and feed and their reference points for action (2015)(2016)(2017)(2018):

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Section: Toxicokineticsmentioning

confidence: 99%

“…No data on the toxicokinetics of MG in humans could be found in the open literature. The only reference to human data is the in vitro capacity of human faecal microflora to almost completely reduce MG to LMG (Henderson et al, 1997).…”

Section: Humansmentioning

confidence: 99%

Malachite green in food

2016

EFS2

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“…The intestinal microflora plays an important role in the metabolism and enterohepatic circulation of drugs (Tancrede 1992). The bacterial flora of the gastrointestinal tract is very complex (M oore & M oore 1995) and any substance administered orally, or entering intestines from bile or blood, becomes a potential substrate for intestinal microor ganisms (Chadwick et al 1992;H enderson et al 1997). The ability of microflora to reduce azo and nitro groups of various xenobiot ics, mostly dyestuffs (Brown 1981), is long known.…”

Section: Reduction Of Oracin By Intestinal Bacteria Of Ratmentioning

confidence: 99%

Stereospecific reduction of the original anticancer drug oracin in rat extrahepatic tissues

Szotáková

Skálová

Jílek

et al. 2003

Journal of Pharmacy and Pharmacology

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The liver is the major site of drug metabolism in the body. However, many drugs undergo metabolism in extrahepatic sites and in the gut wall and lumen. In this study, the distribution and activity of reductases in rat that reduced potential cytostatic oracin to its principal metabolite 11-dihydrooracin (DHO) were investigated. The extension and stereospecificity of oracin reduction to DHO were tested in microsomal and cytosolic fractions from the liver, kidney, heart, lung and wall of small intestine, caecum and large intestine. Intestinal bacterial reduction of oracin was studied as well. The amount of DHO enantiomers was measured by HPLC with Chiralcel OD-R as chiral column. Reductive biotransformation of oracin was mostly stereospecific for (+)-DHO, but the enantiomeric ratio differed significantly among individual tissues and subcellular fractions (from 56% (+)-DHO in heart microsomes to 92% (+)-DHO in liver cytosol). Stereospecificity for (-)-DHO (60%) was observed in bacterial oracin reduction in the lumen of small intestine, caecum and large intestine. Shift of the (+)-DHO/(-)-DHO enantiomeric ratio from 90:10 (in liver subcellular fractions) to 60:40 (in-vivo) clearly demonstrated the importance of the contribution of extrahepatic metabolism to the total biotransformation of oracin to DHO.

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“…Malachite green is highly toxic to mammalian cells; it promotes hepatic tumor formation in rodents and causes reproductive abnormalities in rabbits and fish (RAO 1995, FESSARD et al 1999. Malachite green can be reduced to decolorized leucomalachite green by the intestinal microflora of a variety of animals (HENDERSON et al 1997), and mycobacterial strains (JONE and FALKINHAM III 2003). Leucomalachite green is less toxic than malachite green to both mammalian and bacterial cells (FESSARD et al 1999).…”

mentioning

confidence: 99%

“…The amino acid sequence deduced from mg11 showed a high sequence identity (76%) with the putative oxidoreductase component of Shigella flexneri 2a strain 2457T (WEI et al 2003. The enzymatic reduction of malachite green to leucomalachite green by intestinal microflora results in decolorization of the dye (HENDERSON et al 1997). Decolorization and biodegradation of malachite green by a fungus Phanerochaete chrysosporium occur by an oxidative reaction via N-demethylation catalyzed by lignin peroxidase (BUMPUS and BROCK 1988).…”

mentioning

confidence: 99%

Isolation of Citrobacter sp. mutants defective in decolorizing malachite green

Jang

Lee

Choi

et al. 2004

J. Basic Microbiol.

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To identify genes involved in the decolorization of malachite green, random mutants generated by transposon insertion in the malachite green-decolorizing bacterium, Citrobacter sp. were isolated. The resulting mutant bank yielded 24 mutants with complete defects in their abilities to decolorize malachite green. Southern hybridization with a Tn5 fragment as a probe showed a single hybridized band in 7 mutants, which appeared to have insertions at different sites of the chromosome. The Tn5-inserted genes were isolated and the DNA sequence flanking Tn5 was determined. Based on a sequence database, the putative protein products encoded by the mg genes were identified as follows. mg3, an ABC transporter homolog; mg6, a LysR-type regulatory protein; m11, an oxidoreductase; mg17, a MalG protein in the maltose transport system; and mg21, a sugar kinase. The deduced sequences from two mg genes (mg7 and mg18) showed no significant similarity to any protein with a known function, suggesting that these two mg genes encode unidentified proteins that are responsible for the decolorization of malachite green.

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Reduction of malachite green to leucomalachite green by intestinal bacteria

Cited by 89 publications

References 18 publications

Malachite green in food

Malachite green in food

Stereospecific reduction of the original anticancer drug oracin in rat extrahepatic tissues

Isolation of Citrobacter sp. mutants defective in decolorizing malachite green

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