Search results for "Polycyclic compound"
showing 10 items of 391 documents
Lymphatic absorption of phytosterol oxides in rats
1999
Two of the main classes of oxyphytosterols (7-keto and epoxides) were synthesized from sitosterol and campesterol and given to mesenteric duct-cannulated adult male rats. Lymph was collected during 24 h and was analyzed for oxysterols. The results showed that the lymphatic recovery of the phytosterol oxides was low: 4.7% of the given dose for epoxy derivatives and 1.5% for 7-keto compounds. The campesterol oxides presented a better absorption than the sitosterol oxides. During the process of absorption, the epoxyphytostanols were also partly transformed in campestanetriol and stigmastanetriol.
Rat liver endothelial and Kupffer cell-mediated mutagenicity of polycyclic aromatic hydrocarbons and aflatoxin B1.
1990
The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B1 (AFB1) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB1 and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB1 showed a sligh…
Functional evidence of multidrug resistance transporters (MDR) in rodent olfactory epithelium.
2012
WOS: 000305340700029; International audience; BACKGROUND: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. PRINCIPAL FINDINGS: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices.…
Metabolic Activation of the (+)-S,S- and (−)-R,R-Enantiomers of trans-11,12-Dihydroxy-11,12-dihydrodibenzo[a,l]pyrene: Stereoselectivity, DNA Adduct…
1997
Polycyclic aromatic hydrocarbons require metabolic activation in order to exert their biological activity initiated by DNA binding. The metabolic pathway leading to bay or fjord region dihydrodiol epoxides as ultimate mutagenic and/or carcinogenic metabolites is thought to play a dominant role. For dibenzo[a,l]pyrene, considered as the most potent carcinogenic polycyclic aromatic hydrocarbon, the formation of the fjord region syn- and/or anti-11,12-dihydrodiol 13,-14-epoxide (DB[a,l]PDE) diastereomers has been found to be the principal metabolic activation pathway in cell cultures leading to DNA adducts. In order to further elucidate the stereoselectivity involved in this activation pathway…
Synthesis of fjord region tetraols and their use in hepatic biotransformation studies of dihydrodiols of benzo[c]chrysene, benzo[g]chrysene and diben…
1998
Metabolic activation of the racemic benzo[c]chrysene-trans-9,10-, benzo[g]chrysene-trans-11,12- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiols to fjord region syn- and anti-dihydrodiol epoxides by microsomes of Aroclor 1254-treated Sprague-Dawley rats has been examined. Since the fjord region dihydrodiol epoxides were hydrolytically unstable under the experimental conditions, their enzymatic formation was determined by analyzing the tetraols as their products of acidic hydrolysis upon addition of perchloric acid. The various stereoisomeric tetraols formed were separated by HPLC and identified by co-chromatography with authentic tetraols, which had been prepared by acidic hydrolysis of synt…
Fjord-region diol-epoxides of benzo[c]chrysene are potent inducers of micronuclei in murine bone marrow
1994
Abstract Vicinal diol-epoxides are the best established carcinogenic metabolites of polycyclic aromatic hydrocarbons. Numerous studies have demonstrated their high genotoxic activity in various in vitro test systems. However, in vivo mutagenicity data are not available. The fjor-region diol-epoxides of benzo[ c ]chrysene combine high mutagenic activity in vitro with hydrolytic stability. They were tested for the induction of micronuclei in the bone marrow following intraperitoneal administration to NMRI mice. The anti diasteromer of the diol-epixode enhanced the frequency of micronucleated polycrhomatic erythrocytes strongly (7–19-fold above the value in untreated controls) over a very wide…
Regiospecific oxidation of polycyclic aromatic dihydrodiols by rat liver dihydrodiol dehydrogenase
1991
Rat liver dihydrodiol dehydrogenase (DDH, E.C. 1.3.1.20) has recently been shown to oxidize the highly carcinogenic benz[a]anthracene-3,4- dihydrodiol in an NADP(+)-dependent reaction to its corresponding catechol. The present study is a systematic investigation of the substrate specificity of the purified enzyme towards synthetic trans-dihydrodiol metabolites of phenanthrene, benz[a]anthracene, chrysene, dibenz[a, h]anthracene and benzo[a]pyrene. DDH exhibited a remarkable regiospecificity of enzymatic catalysis with regard to the site of the dihydrodiol moiety of the parent hydrocarbon. M-region- and, with lower efficiency, bay-region dihydrodiols were found to be good substrates of the e…
Massive digoxin intoxication in childhood.
1978
In a 10 year old boy 8 hours after taking about 16 mg beta-acetyl-digoxin a maximum serum digoxin level of 31.8 ng/ml was measured radioimmunologically. This is the highest digitalis level in childhood described to date. The serum potassium level rose to 7.4 mmol/l. Complete atrio-ventricular block, and salves of ventricular premature beats were the most serious rhythm disturbances. The absence of life threatening rhythm disturbances is attributed to the early use of diphenylhydantoin in small frequent doses.
A Novel Risk Locus at 6p21.3 for Epstein-Barr Virus-Positive Hodgkin Lymphoma
2015
Abstract Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls. Results: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interva…
General oxidative stress during doxorubicin-induced cardiotoxicity in rats: Absence of cardioprotection and low antioxidant efficiency of alpha-lipoi…
2012
International audience; To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) and O₂*⁻ (dihydroethidium fluorescence) content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX (+16%), but this was due to ascites. Histologic…