title: Accumulation of phenols and catechols in isolated mouse hepatocytes in starvation or after pretreatment with acetone.
abstract: Conditions leading to the accumulation of unconjugated phenols and catechols were investigated in mouse livers. The formation of unconjugated hydroxylated products of added p-nitrophenol and aniline was investigated in isolated hepatocytes prepared from 48 hr fasted or fed mice or from fed mice after acetone pretreatment. 4-Nitrocatechol and p-aminophenol--the hydroxylated products of p-nitrophenol and aniline--were accumulated in cells prepared from fasting animals, while in cells prepared from fed mice these unconjugated derivatives were not detectable. The accumulation of 4-nitrocatechol and p-aminophenol was also shown in isolated hepatocytes prepared from acetone pretreated fed mice. Inhibition of glucuronidation by N6,O2-dibutyryl cAMP or by D-galactosamine increased the accumulation of 4-nitrocatechol upon addition of p-nitrophenol in cells prepared from fasted mice. Both 48 hr starvation and acetone pretreatment enhanced the activity of microsomal p-nitrophenol and aniline hydroxylase by 300% and 600%, respectively, whereas p-nitrophenol conjugation in isolated hepatocytes as well as in hepatocyte homogenates was decreased by about 80% after 48 hr starvation. Acetone pretreatment did not alter the rate of p-nitrophenol conjugation measured in liver homogenates. It is suggested that a shift from conjugation toward hydroxylation in starvation gives rise to the formation of hazardous metabolites.
authors.affiliation: 1st Institute of Biochemistry, Semmelweis University, Medical School, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Bánhegyi
authors.forename: T
authors.initials: T
authors.lastname: Garzó
authors.forename: F
authors.initials: F
authors.lastname: Antoni
authors.forename: J
authors.initials: J
authors.lastname: Mandl
mesh_terms: D000096:Acetone / Q000494:pharmacology*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002396:Catechols / Q000378:metabolism*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009596:Nitrophenols / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D002396:Catechols; D009596:Nitrophenols; D010636:Phenols; D000096:Acetone; C023650:aniline