Leukocyte and Platelet Depletion Protects the Liver from Damage Induced by Cholestasis and Ischemia–Reperfusion in the Dog

Abstract

Background: Ischemia–reperfusion injury has been studied in various organs. The effects of leukocyte and platelet depletion on cholestasis and ischemia–reperfusion-induced liver damage were evaluated in the dog liver. Methods: The left hepatic duct was ligated for 4 weeks to create a cholestatic lobe. An ischemic condition was produced for 60 min by stopping the peristaltic pump supplying blood to the liver. The metabolism of substances modulated in the liver during cholestasis and I–R was assessed in non-treated and in leukocyte- and platelet-depleted animals. Results: The extraction rate of insulin and indocyanine green decreased during cholestasis and ischemia–reperfusion. Cholestasis accelerated the release of thromboxane A₂ but not prostaglandin I₂ after ischemia-reperfusion. Ischemia–reperfusion accelerated the release of prostaglandin I₂ and thromboxane A₂ from the liver. Further, ischemia-reperfusion increased the ratio of thromboxane A₂ to prostaglandin I₂. Cholestasis promoted an increase in the level of lipid peroxide, a decrease in the glutathione level, and no change in the alpha-tocopherol level. Ischemia–reperfusion caused an increase in the lipid peroxide level, a decrease in the alphatocopherol level, and no change in the glutathione level. Depletion of leukocytes and platelets reduced these changes during cholestasis and ischemia–reperfusion. Conclusions: Depletion of leukocytes and platelets thus appears to protect liver function from cholestasis and ischemia–reperfusion injury by reducing peroxidation of lipids composing the cell membrane and the rate of thromboxane A₂/prostaglandin I₂, which predicts cellular damage, and by increasing the levels of alpha-tocopherol and glutathione, believed to be free radical scavengers.

Key Words:

• Cholestasis
• free radical
• ischemia-reperfusion injury
• leukocyte depletion