Metabolism of 2,4-dinitrotoluene by intestinal microorganisms from rat, mouse, and man

Guest, Derek; Schnell, Stephanie R.; Rickert, Douglas E.; Dent, John G.

doi:10.1016/0041-008x(82)90335-0

Cited by 44 publications

(23 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40 Human faecal samples can also reduce 2,4-dinitrotoluene. 41 However, the genotoxicity of 2-nitrotoluene and 2,6-dinitrotoluene is due to a product of (di)nitrobenzyl alcohol reduction rather than from reduced metabolites and the gut bacteria plays an important role in this toxicity: both 2-nitrotoluene and 2,6-dinitrotoluene are absorbed in the small intestine and metabolised by the liver to 2-nitrobenzyl alcohol and 2,6-dinitrobenzyl alcohol. These compounds are conjugated with glucuronic acid before excretion in the bile.…”

Section: The Gi Microbiota Can Metabolise Environmental Chemicalsmentioning

confidence: 99%

The gut microbiota: a major player in the toxicity of environmental pollutants?

Claus

Guillou

Ellero‐Simatos

2016

npj Biofilms Microbiomes

533

328

View full text Add to dashboard Cite

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants.

show abstract

Section: The Gi Microbiota Can Metabolise Environmental Chemicalsmentioning

confidence: 99%

The gut microbiota: a major player in the toxicity of environmental pollutants?

Claus

Guillou

Ellero‐Simatos

2016

npj Biofilms Microbiomes

533

328

View full text Add to dashboard Cite

show abstract

“…The first step in metabolism in male or female Fischer 344 rats is oxidation at the methyl group to yield dinitrobenzyl alcohols, followed by conjugation with glucuronic acid, preparing the alcohol for bile excretion, which occurs to a much greater degree in male than in female rats (146). Intestinal microflora hydrolyze the glucuronides and reduce one of the nitro groups (to an amino group via nitroso intermediates) (147); the reduced metabolites, aminonitrobenzyl alcohols, are then reabsorbed, whereby, it is postulated, the 2,6 isomer is activated (146). All six dinitrotoluene isomers were metabolized to aminonitrotoluenes by Escherichia coli isolated from human intestinal contents (148), as well as by the intestinal microflora of rats and mice (147).…”

Section: Toxic Effectsmentioning

confidence: 99%

“…Intestinal microflora hydrolyze the glucuronides and reduce one of the nitro groups (to an amino group via nitroso intermediates) (147); the reduced metabolites, aminonitrobenzyl alcohols, are then reabsorbed, whereby, it is postulated, the 2,6 isomer is activated (146). All six dinitrotoluene isomers were metabolized to aminonitrotoluenes by Escherichia coli isolated from human intestinal contents (148), as well as by the intestinal microflora of rats and mice (147). The human urinary metabolites of 2,4-dinitrotoluene in volunteers exposed to dinitrotoluene are 2,4-dinitrobenzoic acid, 2-amino-4-nitrobenzoic acid, 2,4-dinitrobenzyl glucuronide, and 2-(N-acetyl)amino-4-nitrobenzoic acid.…”

Section: Toxic Effectsmentioning

confidence: 99%

Aromatic Nitro and Amino Compounds

Bingham¹,

McGowan²

2012

Patty's Toxicology

View full text Add to dashboard Cite

Logically, aromatic nitro and amino compounds should be discussed together because their toxic responses are often similar due to a common metabolic intermediate. Synthetically, amines are generally derived from nitro compounds, but in some cases nitro compounds can be prepared through amines when other methods fail to afford specific compounds. There are good and bad attributes to these types of compounds. Some act as sensitizers and contingent on physical properties may be absorbed through the skin or mucous membranes. They may also cause methemoglobinemia, depending on such factors as the structure and the particular organism. Some members of this class are known as animal and human carcinogens; for humans, the urinary bladder is the most prominent target organ. Nevertheless, these compounds and their derivatives have enlivened our world through their use as dyestuff intermediates or as photographic chemicals, they alleviate pain as components of widely used analgesics, and they cushion or insulate us through their use in flexible and rigid foams. Other important uses include production of pesticides, including herbicides and fungicides, as ingredients in adhesives, paints and coatings, antioxidants, explosives, optical brighteners, rubber ingredients, and as intermediates in many other products.

show abstract

“…Hydroxylamine and nitroso derivatives have been postulated as intermediates in the reduction; though, they have not been detected. Reductive interme diates of other nitro aromatic compounds such as nitrobenzene [Uehleke, 1963: Kato et al, 1969, 4-nitroquinoline-N-oxide [Poirier and Weisburger, 1974], niridazole [Feller et al, 1971], and 2,4-dinitrotoluene [Guest et al, 1982] have been reported. In the present study, we examined the reduction of CAP and NO-CAP in vitro with rat liver micro somal preparations to determine conditions required for reduction and compare reduc tion rates of CAP and NO-CAP.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Reduction of Chloramphenicol and Nitrosochloramphenicol by Rat Liver Microsomal Preparations

Lim¹,

Yunis²

1983

Pharmacology

View full text Add to dashboard Cite

Chloramphenicol (CAP) and nitrosochloramphenicol (NO-CAP) were metaboli-cally reduced to aromatic amines by rat liver microsomes in vitro. The reduction required anaerobic conditions and was mediated by a NADPH-dependent reductase system. Both CAP and NO-CAP reduction were time and concentration dependent. Compared to CAP, NO-CAP (0.5 mM) reduction was rapid with complete conversion occurring in 90–120 min. At 2.5 mM NO-CAP reduction was depressed. In the presence of NO-CAP (0.05–2.5 mM) CAP metabolism was inhibited from 17 to 91 %. These results indicate that CAP and NO-CAP are metabolized by similar microsomal reductase systems and NO-CAP is unstable, readily reduced further to the aromatic amine.

show abstract

Metabolism of 2,4-dinitrotoluene by intestinal microorganisms from rat, mouse, and man

Cited by 44 publications

References 4 publications

The gut microbiota: a major player in the toxicity of environmental pollutants?

The gut microbiota: a major player in the toxicity of environmental pollutants?

Aromatic Nitro and Amino Compounds

Enzymatic Reduction of Chloramphenicol and Nitrosochloramphenicol by Rat Liver Microsomal Preparations

Contact Info

Product

Resources

About