Linked Life Data

8818569

Source:http://linkedlifedata.com/resource/pubmed/id/8818569

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1997-3-31
pubmed:abstractText
The hepatic and renal toxicity associated with hydrazine treatment has been linked to free radical damage resulting from oxidative metabolism by cytochrome P4502E1 (CYP2E1). Despite this association, there has been little characterization of the effects of hydrazine treatment on the expression of hepatic and renal CYP2E1 or glutathione-S-transferase-alpha (GST-alpha), an enzyme responsible for catalyzing the conjugation of free radicals with reduced glutathione. Therefore, the effects of treatment with hydrazine or one of the therapeutic hydrazines phenelzine and hydralazine on rat hepatic and renal CYP2E1 and GST-alpha expression were investigated. Adult male Sprague-Dawley rats were treated with 0.9% saline vehicle (1 dose ip), hydrazine (100 mg/kg ip), phenelzine (100 mg/kg ip), or hydralazine (25 mg/kg ip). CYP2E1 mRNA and protein levels were monitored by Northern and immunoblot analyses, respectively, and GST-alpha Ya and Yc subunit levels were determined by immunoblot analysis. Hydralazine administration caused a significant (approximately 159%) increase in renal GST-alpha subunit expression. In addition, hydrazine and phenelzine treatment produced substantial elevations (approximately 464% and 566%, respectively) in renal CYP2E1 protein, whereas hydralazine administration did not alter renal CYP2E1 expression. Changes in rat hepatic GST-alpha Ya or Yc subunit levels after treatment with hydrazines phenelzine, or hydralazine were not statistically significant. Similarly, hepatic CYP2E1 levels were not significantly altered after treatment with hydrazine, phenelzine, or hydralazine. Northern blot analysis revealed that the observed increases in renal CYP2E1 protein levels after treatment with hydrazine or phenelzine were not accompanied by concomitant increases in CYP2E1 mRNA. These results suggest that treatment with hydrazine or the therapeutic hydrazine phenelzine significantly increases the expression of rat renal CYP2E1 protein, and that the molecular mechanism responsible for these effects are posttranscriptional in nature.
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
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
734-7
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Effects of hydrazine, phenelzine, and hydralazine treatment on rat hepatic and renal drug-metabolizing enzyme expression.
pubmed:affiliation
Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA.
pubmed:publicationType
Journal Article