Protective effects of diclofenac on liver graft preservation

Abstract

This study aims to evaluate the effect of diclofenac addition to the preservation solution Celsior on liver graft preservation. Liver from Wistar rats were cold flushed in situ, harvested, and then stored in Celsior solution (24 h, 4 °C) supplemented or not with 50 mg/L of diclofenac sodium salt. Reperfusion was performed (120 min, 37 °C) using the isolated perfusion rat liver model. Perfusate samples were collected to evaluate transaminases' activities after cold storage and by the end of reperfusion. To evaluate liver function, bile flow, hepatic clearance of bromosulfophthalein, and vascular resistance were assessed. Diclofenac scavenging property (DPPH assay) as well as oxidative stress parameters (SOD and MPO activities and the concentration of glutathione, conjugated dienes, MDA, and carbonylated proteins) were measured. Transcription factors (PPAR-γ and NF-κB), inflammation (COX-2, IL-6, HMGB-1, and TLR-4), as well as apoptosis markers (Bcl-2 and Bax) were determined by quantitative RT-PCR. Enriching the preservation solution Celsior with diclofenac sodium salt attenuated liver injuries and improved graft function. Oxidative stress, inflammation, and apoptosis were significantly reduced in Celsior + Diclo solution. Also, diclofenac activated PPAR-γ and inhibited NF-κB transcription factors. To decrease graft damage and improve transplant recovery, diclofenac sodium salt may be a promising additive to preservation solution.

Keywords: cold ischemia/reperfusion injury; diclofenac; inflammation; organ preservation solution.