Linked Life Data

10383930

Source:http://linkedlifedata.com/resource/pubmed/id/10383930

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-20
pubmed:abstractText
Molinate undergoes oxidative metabolism forming either ring-hydroxylated metabolites or molinate sulfoxide. Our previous studies strongly implicated the sulfoxidation pathway in molinate-induced testicular toxicity. The present study compares the metabolic capability of rat and human liver microsomes and slices to form either nontoxic ring-hydroxylated metabolites of molinate or the toxic metabolites derived from the sulfoxidation of molinate. Km and Vmax values indicate that sulfoxidation would be the preferred high-dose pathway whereas hydroxylation would predominate at low dose levels in both species. Examination of phase II metabolism of molinate in liver slices reveals greater detoxification of molinate sulfoxide by glutathione conjugation in humans with rats forming less conjugate. Oxidative metabolism of molinate in both rats and humans appears to be mediated by cytochrome P-450 and not flavin monooxygenases as indicated by the use of metabolic inhibitors. Overall, the metabolism of molinate would be via the nontoxic hydroxylation pathway in both species at low doses whereas at high doses, where sulfoxidation would predominate, the human is more capable than the rat to detoxify via glutathione conjugation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
842-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Comparison of human and rat metabolism of molinate in liver microsomes and slices.
pubmed:affiliation
Miller Laboratory, Department of Environmental Toxicology, University of California, Davis, California 95616, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't