COVALENT MODIFICATION OF RAT-LIVER DIPEPTIDYL PEPTIDASE-IV (CD26) BY THE NONSTEROIDAL ANTIINFLAMMATORY DRUG DICLOFENAC

Diclofenac is a nonsteroidal anti-inflammatory drug that has been impl icated in several cases of severe hepatotoxicity. Our previous study s howed 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 dipep tidyl peptidase IV in liver plasma membrane fractions was lowered afte r diclofenac treatment of rats. These results suggest that the hepatot oxicity associated with diclofenac might be due, in part, to the coval ent modification of dipeptidyl peptidase IV.