Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin

Burian, Maria; Freudenstein, Johannes; Tegtmeier, M.; Naser-Hijazi, Belal; Zepelin, Hans-Heinrich Henneicke-von; Legrum, Wolfgang

doi:10.5414/cpp41141

Cited by 27 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the nine patients showing evidence of hepatotoxicity only one had the variant allele, eight being wild-type homozygotes [66]. This result indicates that a single copy of a variant CYP2A6 allele does not confer susceptibility to liver dysfunction in patients treated with coumarin [66].…”

Section: Polymorphisms Of Influencementioning

confidence: 88%

“…This result indicates that a single copy of a variant CYP2A6 allele does not confer susceptibility to liver dysfunction in patients treated with coumarin [66]. Since the conversion of o-HPA to o-HPAA is catalyzed by aldehyde dehydrogenase, polymorphisms known to occur in this enzyme could contribute to interindividual differences in sensitivity toward coumarin induced toxicity, although this remains to be demonstrated.…”

Section: Polymorphisms Of Influencementioning

confidence: 93%

See 1 more Smart Citation

Molecular mechanisms of toxicity of important food-borne phytotoxins

Rietjens¹,

Martena

Boersma

et al. 2005

Mol. Nutr. Food Res.

103

View full text Add to dashboard Cite

At present, there is an increasing interest for plant ingredients and their use in drugs, for teas, or in food supplements. The present review describes the nature and mechanism of action of the phytochemicals presently receiving increased attention in the field of food toxicology. This relates to compounds including aristolochic acids, pyrrolizidine alkaloids, beta-carotene, coumarin, the alkenylbenzenes safrole, methyleugenol and estragole, ephedrine alkaloids and synephrine, kavalactones, anisatin, St. John's wort ingredients, cyanogenic glycosides, solanine and chaconine, thujone, and glycyrrhizinic acid. It can be concluded that several of these phytotoxins cause concern, because of their bioactivation to reactive alkylating intermediates that are able to react with cellular macromolecules causing cellular toxicity, and, upon their reaction with DNA, genotoxicity resulting in tumors. Another group of the phytotoxins presented is active without the requirement for bioactivation and, in most cases, these compounds appear to act as neurotoxins interacting with one of the neurotransmitter systems. Altogether, the examples presented illustrate that natural does not equal safe and that in modern society adverse health effects, upon either acute or chronic exposure to phytochemicals, can occur as a result of use of plant- or herb-based foods, teas, or other extracts.

show abstract

Section: Polymorphisms Of Influencementioning

confidence: 88%

Section: Polymorphisms Of Influencementioning

confidence: 93%

Molecular mechanisms of toxicity of important food-borne phytotoxins

Rietjens¹,

Martena

Boersma

et al. 2005

Mol. Nutr. Food Res.

103

View full text Add to dashboard Cite

show abstract

“…Recently, in the literature exceeding reports and experiments dealing with the question of hazard factor for coumarin have focused on animal and its estimation based on scientific information [32][33][34] . Nonetheless, significant human assays are available now on the hepatoxycity of using coumarin as a pharmaceutical cure [35][36][37] . These implementations in the regulations related with the use of coumarin on European level are evidence for understanding better that it is toxic.…”

Section: Discussionmentioning

confidence: 99%

In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1)

Gökçe

Gençer

Arslan

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1-20) on purified PON1 activity was investigated. Among these compounds, derivatives 11-20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC 50 ¼ 35 and 34 mM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

show abstract

“…Metabolism and toxicokinetic studies Burian et al (2003) concluded that there is no evidence that the polymorphism in CYP2A6* 2 is a determinant of coumarin-associated liver dysfunction in humans. In contrast, Farinola and Piller (2007) speculated that a reduction in 7-hydroxylation will lead to shunting of metabolism into other pathways for coumarin.…”

Section: Studies Which Have Been Reconsideredmentioning

confidence: 99%

“…However, the basis for this conclusion is unclear because no homozygous individuals with both alleles defective were represented in the studied group, and it has been described that homozygoity for the defective allele has much greater impact on coumarin metabolism than heterozygoity (Hadidi, 1997). In addition, in the study by Burian et al (2003) data on other pathways of coumarin metabolism were not collected. The EFSA (2004) therefore concluded that hepatotoxicity as observed in rodents and dogs should be taken into account in setting a TDI.…”

Section: Annex 1 Toxicity Data From 1994 Scf Opinionmentioning

confidence: 99%

Coumarin in flavourings and other food ingredients with flavouring properties ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC)

2008

EFS2

View full text Add to dashboard Cite

The Panel considered the toxicity studies and the studies on the metabolism of coumarin in humans with CYP2A6 polymorphism that have become available since the last opinion of 2004, as well as clinical studies, and concluded to maintain the TDI of 0.1 mg coumarin/kg bw allocated in the 2004 opinion.Considering the toxicity data on coumarin, including the timing of the onset of liver effects, recovery of these effects after cessation of exposure to coumarin and the elimination half-life, the Panel concluded that exposure to coumarin resulting in an intake 3 times higher than the TDI for one to two weeks is not of safety concern.

show abstract

Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin

Cited by 27 publications

References 0 publications

Molecular mechanisms of toxicity of important food-borne phytotoxins

Molecular mechanisms of toxicity of important food-borne phytotoxins

In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1)

Coumarin in flavourings and other food ingredients with flavouring properties ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC)

Contact Info

Product

Resources

About