Linked Life Data

16630638

Source:http://linkedlifedata.com/resource/pubmed/id/16630638

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-6-9
pubmed:abstractText
The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by (3)H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of (14)C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor detoxification appears to play a decisive role in the development of this tolerance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration.
pubmed:affiliation
Department of Toxicology, College of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue, Sugar Hall #306, Monroe, LA 71209-0495, USA. sanand@rx.uga.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't