Linked Life Data

9344622

Source:http://linkedlifedata.com/resource/pubmed/id/9344622

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-12-16
pubmed:abstractText
Treatment of rats with para-aminophenol (PAP) (300 mg/kg ip) produced decreases in renal nonprotein sulfhydryl (NPSH) content, oxygen consumption, and adenine nucleotide concentrations 2-4 hr following administration. In contrast, incubation of rat renal tubules with up to 1 mm PAP for 4 hr produced inconsistent changes in renal tubules. This discrepancy suggested that extrarenal metabolism of PAP may be involved in PAP bioactivation and nephrotoxicity. We designed the present studies to test the hypothesis that hepatic metabolism of PAP potentiates the effects of PAP on renal tubules. Incubation of renal tubules with 0.5 mm PAP and 10 mg protein from hepatic postmitochondrial supernatant (S9 fraction) in the absence of glutathione (GSH) for 4 hr did not alter renal oxygen consumption or adenine nucleotide metabolite concentrations. We observed no changes when we incubated tubules with 0.5 mm PAP and 1 mm GSH in the absence of hepatic S9 fraction. However, incubation of renal tubules with 0.5 mm PAP, 1 mm GSH, and 10 mg hepatic S9 protein for 4 hr significantly decreased renal oxygen consumption and adenosine triphosphate and total nucleotide concentrations. These data suggest that the effects of PAP in renal tubules may be potentiated by enzymatic metabolism of PAP, possibly involving oxidation and GSH conjugation. From experiments using hepatic microsomes or cytosol instead of S9 fraction, we found that changes were produced when we incubated tubules with PAP in the presence of hepatic microsomes, but not cytosol. These data suggest that hepatic microsomal metabolism of PAP may contribute to the production of changes in renal tubules in vitro. PAP-induced changes in renal proximal tubules were prevented when we included a beta-nicotinamide adenine dinucleotide phosphate (NADPH) generating system in the incubation medium. The protective effect of NADPH persisted when microsomes were inactivated by incubation with 1-aminobenzotriazole, a cytochrome P450 inhibitor. These data suggest that cytochrome P450-dependent oxidation is not involved in the production or prevention of PAP-induced changes in renal tubules. The enzyme(s) responsible for PAP bioactivation and the mechanism(s) by which NADPH protects renal tubules from PAP-induced decrements in oxygen consumption and adenine nucleotide concentrations are currently unclear.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0272-0590
pubmed:author
pubmed:copyrightInfo
Copyright 1997 Society of Toxicology.
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Coincubation of rat renal proximal tubules with hepatic subcellular fractions potentiates the effects of para-aminophenol.
pubmed:affiliation
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, 600 S. 43rd Street, Philadelphia, Pennsylvania 19104-4495, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.