LEUKOCYTE AND PLATELET DEPLETION PROTECTS THE LIVER FROM DAMAGE-INDUCED BY CHOLESTASIS AND ISCHEMIA-REPERFUSION IN THE DOG

Background: Ischemia-reperfusion injury has been studied in various or gans. The effects of leukocyte and platelet depletion on cholestasis a nd ischemia-reperfusion-induced liver damage were evaluated in the dog liver. Methods: The left hepatic duct was ligated for 4 weeks to crea te a cholestatic lobe. An ischemic condition was produced for 60 min b y stopping the peristaltic pump supplying blood to the liver. The meta bolism of substances modulated in the liver during cholestasis and I-R was assessed in non-treated and in leukocyte- and platelet-depleted a nimals. Results: The extraction rare of insulin and indocyanine green decreased during cholestasis and ischemia-reperfusion. Cholestasis acc elerated the release of thromboxane A(2) but not prostaglandin I-2 aft er ischemia-reperfusion. Ischemia-reperfusion accelerated the release of prostaglandin I-2 and thromboxane A(2) from the liver. Further, isc hemia-reperfusion increased the ratio of thromboxane A(2) to prostagla ndin I-2. Cholestasis promoted an increase in the level of lipid perox ide, a decrease in the glutathione level, and no change in the alpha-t ocopherol level. Ischemia-reperfusion caused an increase in the lipid peroxide level, a decrease in the alpha-tocopherol level, and no chang e in the glutathione level. Depletion of leukocytes and platelets redu ced these changes during cholestasis and ischemia-reperfusion. Conclus ions: Depletion of leukocytes and platelets thus appears to protect li ver function from cholestasis and ischemia-reperfusion injury by reduc ing peroxidation of lipids composing the cell membrane and the rate of thromboxane A(2)/prostaglandin I-2, which predicts cellular damage, a nd by increasing the levels of alpha-tocopherol and glutathione, belie ved to be free radical scavengers.