Effect of diclofenac, a non-steroidal anti-inflammatory 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 rat. 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 (O2-) or hydroxyl radicals (.OH), nor a suppressive ability for the NADPH-dependent LPO of microsomes. In contrast, alpha-toc. trapped both DPPH and O2-, 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.
Takayama
F
F
Department of Pharmacology, Oita Medical University, Japan.
Egashira
T
T
Yamanaka
Y
Y
D000818:Animals; D004008:Diclofenac / Q000627:therapeutic use*; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010713:Phosphatidylcholines / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D014810:Vitamin E / Q000627:therapeutic use
D016166:Free Radical Scavengers; D010713:Phosphatidylcholines; C057590:phosphatidylcholine hydroperoxide; D014810:Vitamin E; D004008:Diclofenac; D009249:NADP