Disease relevance of Paraxenol

• The rabbit liver UDP-glucuronosyltransferase (UGT) cDNAs that encode the 4-hydroxybiphenyl UGT2B13 and 4-nitrophenol UGT1A6 have been cloned into baculovirus [1].
• Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4'-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7 [2].

Psychiatry related information on Paraxenol

• There was a large individual difference in the microsomal glucuronidation of cis-HO-TAM, which correlated well with glucuronidation of 4-hydroxybiphenyl by human liver microsomes [3].

High impact information on Paraxenol

• Slight increases in benzo(a)pyrene hydroxylation and 4-hydroxybiphenyl glucuronidation were also evident in diploid cells [4].
• Expressed UGT2B16 protein in COS-1 cells was active toward 4-hydroxybiphenyl, similar to that of UGT2B13 [5].
• A lambda clone containing the entire gene and flanking sequences for a form of UDP-glucuronosyltransferase (UDPGTr-2) that glucuronidates testosterone and the foreign compounds, 4-hydroxybiphenyl and chloramphenicol, has been isolated from a rat liver genomic library [6].
• A phenobarbital-inducible rat hepatic microsomal UDP-glucuronosyltransferase (UDPGT) that catalyzes the glucuronidation of 4-hydroxybiphenyl (4-HBP) has been purified to homogeneity [7].
• Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: conformationally restricted structural probes [8].

Biological context of Paraxenol

• Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls [9].
• The first step in the biotransformation pathway was the monohydroxylation of the biaryl compound to produce 2-, 3-, and 4-hydroxybiphenyl [10].
• 1. Sulphotransferase is an important detoxication pathway of hydroxybiphenyls and the kinetics of sulphotransferase activity were studied in human liver, ileum and colon mucosae, lung, kidney, urinary bladder mucosa and brain using 0-, m- and p-hydroxybiphenyl as substrates [11].
• In addition, the peroxidation of the acridan substrate was found to be very slow at pH 5.6 in the absence of the enhancer, p-phenylphenol, whereas in its presence a rapid degradation of the acridan substrate was observed [12].
• Whereas the rate of the first oxidation step at 4-chlorobiphenyl seems to be diminished by the decreased bioavailability of the compound, no considerable differences were observed between the degradation of 4-chloro-4'-hydroxybiphenyl and 4-hydroxybiphenyl [13].

Anatomical context of Paraxenol

• 4-Hydroxybiphenyl UDPGT was separated from morphine UDPGT using a chromatofocusing procedure for Emulgen 911-solubilized microsomes [14].
• Cytotoxic effects of biphenyl and hydroxybiphenyls on isolated rat hepatocytes [15].
• Monoclonal antibodies against purified rat liver 4-hydroxybiphenyl UDP-glucuronosyltransferase were developed using the hybridoma technology [16].
• In contrast, GT activity towards 4-hydroxybiphenyl was much lower than in hepatocytes or bile duct cells (0.04- and 0.03-fold) [17].
• 2. 2,3- and phenylhydroquinone, which induced DNA single-strand scission in the presence of 1 microM CuCl2, were the most cytotoxic chemicals examined to cultured mammalian cell lines among o-phenylphenol, m-phenylphenol, p-phenylphenol, 2,2'-, 4,4'-, 2,3- and phenylhydroquinone [18].

Associations of Paraxenol with other chemical compounds

• However, expression of the UGT2B13 cDNA in COS-1 cells displayed no activity in the presence of estrone but efficiently conjugated 4-hydroxybiphenyl [19].
• Cunninghamella elegans grown on Sabouraud dextrose broth transformed biphenyl to produce 2-, 3- and 4-hydroxybiphenyl, as well as 4,4'-dihydroxybiphenyl as free phenols [20].
• An increase in UDP-glucuronosyltransferase activity toward 4-methylumbelliferone and 4-hydroxybiphenyl was noted in the intestine [21].
• Influence of the sulphation inhibitor, 2,6-dichloro-4-nitrophenol, on the production and conjugation, of 4-hydroxybiphenyl generated from 4-methoxybiphenyl by rat isolated hepatocytes [22].
• These results suggest that a form of UDP-glucuronosyltransferase, which catalyzes the glucuronidations of serotonin and these xenobiotics except for 4-hydroxybiphenyl, is induced during the development of hepatitis in the LEC rat [23].

Gene context of Paraxenol

• Conjugases such as UDP- glucuronosyltransferases with substrates 3-OH benzo(a)pyrene (UGT1) and 4-hydroxybiphenyl (UGT2) and glutathione S-transferase (GST) with substrate 1-chloro-2,4-dinitrobenzene were higher by 72, 69, and 33% in RF and 28, 38, and 24% in rRF groups, respectively [24].
• Based on this work we conclude that morphine and 4-hydroxybiphenyl can react with separate UDPGT isoforms [14].
• Small intestinal morphine and 4-hydroxybiphenyl UGT activities appeared to be moderately (2- to 3-fold) induced by oral treatment with BNF [25].
• The method requires only 0.3 mg of protein and its sensitivity was as low as 0.36 nmol metabolite formed/mg protein/h (0.32 pmol injected) for 2-, 3-, and 4-hydroxybiphenyl [26].
• The following enzyme activities were determined: cytochrome P-448-dependent ethoxyresorufin O-deethylase (ERDE) and cytochrome P-450-dependent aldrin epoxidase (AE), and, furthermore, the GT form(s) metabolizing 3-hydroxybenzo(a)pyrene (GT1) and the GT form(s) metabolizing 4-hydroxybiphenyl (GT2) [27].

Analytical, diagnostic and therapeutic context of Paraxenol

• Metabolite structures were identified by mass spectrometry, dechlorination to identifiable hydroxybiphenyls, and HPLC retention times [28].
• In addition this metabolite had properties identical to 4-hydroxybiphenyl when analyzed by thin-layer and high-pressure liquid chromatography [29].
• 4-Hydroxybiphenyl was identified from the most active fraction using gas chromatography/mass spectroscopy [30].

References