Track topics on Twitter Track topics that are important to you
4-Nonylphenol (4-NP) is a well-known toxic environmental contaminant. The major objective of the present study was to identify reactive metabolites of 4-NP. Following incubations of 4-NP with NADPH- and GSH-supplemented human liver microsomes, 6 GSH conjugates, along with 19 oxidized metabolites, were detected by UPLC/Q-TOF mass spectrometry utilizing the mass defect filter method. Several authentic key metabolite standards were chemically synthesized for structural identification. Three GSH conjugates were found to derive from quinone methide intermediates, and the other three resulted from ortho-benzoquinone intermediates. Conjugation of the quinone methides with GSH produced benzylic-orientated GSH conjugates by 1,6-addition, while the reaction of the ortho-benzoquinone intermediates offered aromatic-orientated GSH conjugates. The conversion of 4-NP to the quinone methides and ortho-hydroquinones required cytochromes P450, specifically CYPs1A2, 2C19, 2D6, 2E1, and 3A4, while the oxidation of ortho-benzohydroquinones to the corresponding benzoquinones was apparently independent of microsomal enzymes. The ortho-benzoquinone derived from 4-NP was isomerized to the corresponding hydroxyquinone methide, and the former dominated the latter at a rate of approximately 20:1. The findings of the quinone methide and benzoquinone metabolites intensified the concern on the impact of 4-NP exposure on human health.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, and Center for Developmental Therapeutics, Seattle Children's Research Institute, Division of Gastroenterology, Department of Pediatrics, University of Washington, Seattle
This article was published in the following journal.
Name: Chemical research in toxicology
The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and su...
Ferrociphenols (FCs) and their oxidized, electrophilic quinone methide metabolites (FC-QMs) are organometallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evalu...
Nonylphenol is a hydrophobic endocrine disrupting compound, which can inhibit the growth of sewage bacteria in biological processes. This study investigated the degradation of 4-n-nonylphenol (NP) in ...
Quinones are highly reactive molecules that readily undergo either one- or two-electron reduction. One-electron reduction of quinones or their derivatives by enzymes such as cytochrome P450 reductase ...
The first total synthesis of (+)-cytosporolide A was achieved by a biomimetic hetero-Diels-Alder reaction of (-)-fuscoatrol A with o-quinone methide generated from (+)-CJ-12,373. The dienophile, highl...
The objective of the study is to compare the oral contraceptive (OC) SH T00658ID over Ortho Tri-Cyclen Lo administered for 13 cycles to healthy female volunteers between 18 and 50 years of...
Orthokeratology (ortho-k) is a clinical technique that uses reverse geometry rigid gas permeable contact lens exerting positive pressure on the central cornea to temporary reduce refractiv...
The purpose of this study is to assess the effect of BMS-790052 on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects.
Pathologic tooth migration (PTM) is a common complication of advanced periodontitis and often motivation for patients to seek orthodontic therapy. While it has been clearly established tha...
The purpose of this study is to administer a combined oral contraceptive (ethinyl estradiol and norgestimate) with the HIV treatment of atazanavir and ritonavir to healthy females in order...
A plant genus of the family TAXODIACEAE. Members contain taxodione and taxodone, which are diterpenoid quinone methide tumor inhibitors.
NAD(P)H:(quinone acceptor) oxidoreductases. A family that includes three enzymes which are distinguished by their sensitivity to various inhibitors. EC 126.96.36.199 (NAD(P)H DEHYDROGENASE (QUINONE);) is a flavoprotein which reduces various quinones in the presence of NADH or NADPH and is inhibited by dicoumarol. EC 188.8.131.52 (NADH dehydrogenase (quinone)) requires NADH, is inhibited by AMP and 2,4-dinitrophenol but not by dicoumarol or folic acid derivatives. EC 184.108.40.206 (NADPH dehydrogenase (quinone)) requires NADPH and is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol.
One ring heterocyclic compounds defined by C6H7NO. Permitted are any degree of hydrogenation, any substituents and any ortho-fused or ortho-peri-fused ring systems.
A preconceived judgment made without adequate evidence and not easily alterable by presentation of contrary evidence.
A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...