Effect of verapamil on hepatic ischemia/reperfusion injury.
Alterations in cellular calcium homeostasis are a critical factor in the pathogenesis of hepatic ischemic damage and may mediate oxygen free radical injury during the reperfusion period. We investigated the effect of the calcium channel blocker verapamil on hepatic ischemia/reperfusion injury in normal rats and rats sensitized to oxidative injury by chemical depletion of the endogenous antioxidant glutathione. Forty-five minutes of complete hepatic ischemia followed by reperfusion caused an increase in the serum glutamic pyruvic transaminase (SGPT) level and a decline in the endogenous hepatic glutathione level but no increase in hepatic lipid peroxidation products. Chemical depletion of hepatic glutathione with diethylmaleate did not induce hepatocellular injury but augmented hepatic ischemia/reperfusion-induced SGPT release and promoted lipid peroxidation. Pretreatment with the calcium entry blocker verapamil protected against the ischemia/reperfusion-induced drop in hepatic glutathione but did not reduce SGPT release in normal rats. In rats sensitized to oxidative injury by chemical depletion of endogenous glutathione, the calcium channel blocker verapamil protected against ischemia/reperfusion-induced lipid peroxidation and reduced the release of SGPT. These findings indicate that the rat liver is protected against oxidative injury after short periods of total ischemia by its rich supply of endogenous glutathione. A beneficial effect of verapamil occurs only in rats sensitized to oxidative injury, suggesting that the calcium channel blocker protects against oxygen radical attack.
Stein
H J
HJ
Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa.
Oosthuizen
M M
MM
Hinder
R A
RA
Lamprechts
H
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005978:Glutathione / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D014700:Verapamil / Q000627:therapeutic use*
D008298:Maleates; D017382:Reactive Oxygen Species; D014700:Verapamil; D000410:Alanine Transaminase; C014476:diethyl maleate; D005978:Glutathione