Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1979-6-29
pubmed:abstractText
The effects of chloroform on some rat microsomal enzyme activities were studied in vitro. Maximum inhibition of oxygen consumption, NADPH oxidase and NADPH-cytochrome c reductase was observed at 0.5 mM chloroform; prior metabolization of CHCl3 by microsomal monooxygenases increased inhibition by about 50% at 0.2-0.5 mM chloroform. Higher concentrations produced a paradoxical reversal of inhibition, whereas p-nitroanisole demethylase was steadily inhibited by about 50% up to 10 mM chloroform. Irreversible binding of 14CHCl3 was confirmed to depend on chloroform metabolization by monooxygenases. The increased irreversible binding due to phenobarbital induction is accompanied by a diminished affinity towards chloroform as shown by increased KM of irreversible binding, and a higher spectral dissociation constant KS. Aminoacids with nucleophilic functions (histidine, cysteine) partially prevented the irreversible binding of chloroform metabolites to microsomes; non-volatile radioactive derivatives were recovered in trichloracetic acid supernatants when microsomes were incubated with cysteine, but not with histidine. Phosgene has been demonstrated as a biological metabolite of chloroform: its possible reactions with nucleophilic groups of macromolecules, water and added aminoacids partly explain these experimental data. Similar results were obtained with human microsomes, showing that chloroform hepatotoxicity in man could involve the same mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1979
pubmed:articleTitle
Biotransformation of chloroform by rat and human liver microsomes; in vitro effect on some enzyme activities and mechanism of irreversible binding to macromolecules.
pubmed:publicationType
Journal Article, In Vitro