Highlighted Papers Circulating Protein Adducts in Diclofenac Patients

Mass spectrometric characterization of circulating covalent protein adducts derived from a drug acyl glucuronide metabolite: multiple albumin adductions in diclofenac patients.

Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and hu...

Mass spectrometric characterization of protein adducts of multiple cytochrome P450-dependent reactive intermediates of diclofenac to human glutathione-S- transferase P1-1 Adapted from: Mass spectrometric characterization of protein adducts of multiple cytochrome P450-dependent reactive intermediates of diclofenac to human glutathione-S-transferase P1-1

Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2).

Previous work demonstrates that the reactive acyl glucuronide of the nonsteroidal antiinflammatory drug diclofenac forms selective protein adducts in the liver, which may play a causal role in the pathogenesis of diclofenac-associated liver toxicity. Because glucuronide conjugates can be exported into the bile, we explored the role of diclofenac glucuronide hepatobiliary transport in the format...

The Highlighted Roles of Metabolic and Cellular Response to Stress Pathways Engaged in Circulating hsa-miR-494-3p and hsa-miR-661 in Alzheimer’s Disease

Background: Among different roles of miRNAs in AD pathogenesis, hsa-miR-494-3p and hsa-miR-661 functions are poorly understood. Methods: To obtain the gene targets, gene networks, gene ontology, and enrichment analysis of the two miRNAs, some web servers were utilized. Furthermore, the expressions of these miRNAs were analyzed by qRT-PCR in 36 blood sera, including 18 Alzheimer’s patients and 1...

In vivo perturbation of rat hepatocyte canalicular membrane function by diclofenac.

Clinical use of diclofenac is associated with a small but significant incidence of hepatotoxicity. It has been reported that in vivo diclofenac treatment results in decreased activity of the extracellular canalicular membrane protein dipeptidylpeptidase IV in rats as a consequence of protein adduct formation by its electrophilic metabolite diclofenac acyl glucuronide. The present study has inve...