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Covalent modification of rat liver dipeptidyl peptidase IV (CD26) by the nonsteroidal anti-inflammatory drug diclofenac.

Authors
  • Hargus, S J
  • Martin, B M
  • George, J W
  • Pohl, L R
Type
Published Article
Journal
Chemical research in toxicology
Publication Date
Dec 01, 1995
Volume
8
Issue
8
Pages
993–996
Identifiers
PMID: 8605291
Source
Medline
License
Unknown

Abstract

Diclofenac is a nonsteroidal anti-inflammatory drug that has been implicated in several cases of severe hepatotoxicity. Our previous study showed that diclofenac metabolites bound covalently and selectively to rat liver plasma membrane proteins with estimated monomeric masses of 110, 140, and 200 kDa. We report here that we have identified the 110 kDa diclofenac-labeled protein in rat liver as dipeptidyl peptidase IV, also known as CD26. In addition, we found that the activity of dipeptidyl peptidase IV in liver plasma membrane fractions was lowered after diclofenac treatment of rats. These results suggest that the hepatotoxicity associated with diclofenac might be due, in part, to the covalent modification of dipeptidyl peptidase IV.

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