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1.
Arch Toxicol ; 98(3): 837-848, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38182911

ABSTRACT

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters) and recombinant human hepatic UGTs (10 isoforms) were examined. TBBPA glucuronidation by the liver microsomes followed the Michaelis-Menten model kinetics in humans, rats, and hamsters and the biphasic model in monkeys, dogs, minipigs, and mice. The CLint values based on the Eadie-Hofstee plots were mice (147) > monkeys (122) > minipigs (108) > humans (100) and rats (98) > dogs (81) > hamsters (47). TCBPA glucuronidation kinetics by the liver microsomes followed the biphasic model in all species except for minipigs, which followed the Michaelis-Menten model. The CLint values were monkeys (172) > rats (151) > mice (134) > minipigs (104), dogs (102), and humans (100) > hamsters (88). Among recombinant human UGTs examined, UGT1A1 and UGT1A9 showed higher TBBPA and TCBPA glucuronidation abilities. The kinetics of TBBPA and TCBPA glucuronidation followed the substrate inhibition model in UGT1A1 and the Michaelis-Menten model in UGT1A9. The CLint values were UGT1A1 (100) > UGT1A9 (42) for TBBPA glucuronidation and UGT1A1 (100) > UGT1A9 (53) for TCBPA glucuronidation, and the activities at high substrate concentration ranges were higher in UGT1A9 than in UGT1A1 for both TBBPA and TCBPA. These results suggest that the glucuronidation abilities toward TBBPA and TCBPA in the liver differ extensively across species, and that UGT1A1 and UGT1A9 expressed in the liver mainly contribute to the metabolism and detoxification of TBBPA and TCBPA in humans.


Subject(s)
Chlorophenols , Liver , Microsomes, Liver , Polybrominated Biphenyls , Humans , Animals , Rats , Mice , Dogs , Swine , Swine, Miniature/metabolism , Microsomes, Liver/metabolism , Liver/metabolism , Glucuronosyltransferase/metabolism , Animals, Laboratory/metabolism , Protein Isoforms/metabolism , Haplorhini/metabolism , Kinetics , Glucuronides/metabolism , Uridine Diphosphate/metabolism
2.
In. Carvalheiro, José da Rocha; Azevedo, Nara; Araújo-Jorge, Tania C. de; Lannes-Vieira, Joseli; Klein, Lisabel. Clássicos em doença de Chagas: história e perspectivas no centenário da descoberta. Rio de Janeiro, Fiocruz, 2009. p.477-485, tab.
Monography in Portuguese | LILACS | ID: lil-535925

ABSTRACT

Revisões históricas aos avanços científicos para o controle da doença, o Simpósio Internacional Comemorativo do Centenário da Descoberta da Doença de Chagas (1909-2009).


Subject(s)
Animals , Mice , Chagas Disease/history , Chagas Disease/immunology , Chagas Disease/therapy , Research , Nitrofurazone/therapeutic use , Trypanosoma cruzi/immunology , Trypanosoma cruzi/chemistry , Animals, Laboratory/metabolism , Chagas Disease/drug therapy , History of Medicine , Therapies, Investigational/history , Therapies, Investigational/methods
5.
Corrientes; Facultad de Medicina [UNNE]; 1967. 201 p. (60607).
Monography in Spanish | BINACIS | ID: bin-60607
6.
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