Linked Life Data

15013858

Source:http://linkedlifedata.com/resource/pubmed/id/15013858

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-3-11
pubmed:abstractText
gamma-Glutamyltransferase (gamma-GT) catalyzes the hydrolysis of glutathione, glutathione S-conjugates, and gamma-substituted l-glutamate derivatives. Acivicin is an irreversible inhibitor of gamma-GT that has been used to study the role of gamma-GT in glutathione homeostasis and glutathione-dependent bioactivation reactions. The present studies were undertaken because of reported conflicting effects of acivicin on the nephrotoxicity of some haloalkenes that undergo glutathione-dependent bioactivation. The objective of this study was to test the hypothesis that acivicin may alter renal glutathione concentrations; acivicin-induced changes in renal glutathione concentrations may alter the susceptibility of the kidney to the nephrotoxic effects of haloalkenes. Hence, diurnal and acivicin-induced changes in renal and hepatic glutathione concentrations along with renal and hepatic gamma-GT activities were investigated. The previously observed diurnal variations in hepatic glutathione concentrations in fed rats were confirmed, but no diurnal variations were observed in renal glutathione concentrations or in renal or hepatic gamma-GT activities. Renal and hepatic glutathione concentrations and gamma-GT activities were measured in tissue homogenates from rats given 0, 0.1, or 0.2 mmol acivicin/kg (i.p.) and killed 0, 2, 4, 8, 12, or 24 hr later. Renal glutathione concentrations were increased above control values in acivicin-treated rats, whereas acivicin had no effect on hepatic glutathione concentrations. Renal gamma-GT activities decreased within 2 hr after giving acivicin and remained decreased for 24 hr. Acivicin had no effect on hepatic gamma-GT activities, except at 24 hr after treatment when values in acivicin-treated rats were elevated compared with controls. Although the present studies do not afford an explanation of the mechanism whereby acivicin increases the nephrotoxicity of some haloalkenes, they do indicate that acivicin is not a reliable probe to investigate the role of gamma-GT in haloalkene-induced nephrotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Acivicin-induced alterations in renal and hepatic glutathione concentrations and in gamma-glutamyltransferase activities.
pubmed:affiliation
Department of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.