EFFECT OF DICLOFENAC, A NONSTEROIDAL ANTIINFLAMMATORY DRUG, ON LIPID-PEROXIDATION CAUSED BY ISCHEMIA-REPERFUSION IN RAT-LIVER

The present study investigated the effects of diclofenac sodium (Dic Na) on lipid peroxidation (LPO) and liver injury in ischemia-reperfused rats. LPO was estimated from the levels of phosphatidylcholine hydroperoxide (PCOOH), a primary peroxidative product of phosphatidylcholine. Hepatic ischemia-reperfusion induced significant elevation of plasma PCOOH and caused liver injury in rats. Rats were treated daily with Dic Na or alpha-tocopherol (alpha-toc.), p.o., for 5 days and once at 1 hr prior to induction of ischemia. Both substances prevented LPO from decreasing the plasma PCOOH level, and they significantly suppressed the elevation of serum GOT and LDH, in a dose-dependent manner. Dic Na was able to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), but did not show radical-trapping ability for superoxide anion (O-2(-)) or hydroxyl radicals ( OH), nor a suppressive ability for the NADPH-dependent LPO of microsomes. In contrast, alpha-toc. trapped both DPPH and O-2(-), but not OH, and it inhibited the NADPH dependent LPO in vitro. These results suggest that Dic Na may suppress liver injury caused by ischemia-reperfusion through stable radical scavenging and the inhibition of superoxide production in activated phagocytes, both of which may restrain the induction and progression of oxidative stress.