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.
Department of Pharmacology, Oita Medical University, Japan.
F
F
Takayama
T
T
Egashira
Y
Y
Yamanaka
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