EFFECTS OF BLOCKADE OF KUPFFER CELLS BY GADOLINIUM CHLORIDE ON HEPATOBILIARY FUNCTION IN COLD ISCHEMIA-REPERFUSION INJURY OF RAT-LIVER

The mechanisms of liver injury from cold storage and reperfusion are n ot completely understood, The aim of the present study was to investig ate: 1) whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GadCl) modulates cold ischemia-reperfusion injury of rat liv er; and 2) whether cold storage of rat liver involves injury to biliar y epithelial cells (BECs), Hepatobiliary function was assessed using a n isolated perfused rat liver model. Compared with control livers, in livers subjected to cold storage at 4 degrees C in Euro-Collins soluti on (EC) for 18 hours or in University of Wisconsin solution (UW) for 4 8 hours, portal flow was lower and resistance significantly higher, ta urocholate (TC) and bromosulfophthalein (BSP) elimination were markedl y impaired, bile flow was reduced, and lactate dehydrogenase (LDH) lea kage into the perfusate was increased, Pretreatment of rats with GadCl , a selective KC toxicant, abrogated disturbances of the microcirculat ion in both models, but it did not influence viability and functional parameters of the liver, Most of the parameters studied in livers stor ed in UW solution for 18 hours were not significantly different from t hose found in control livers. As to biliary activity of gamma-glutamyl transferase (GGT), as an index of BEC integrity, it was increased wit h increasing time of cold storage, The reabsorption of glucose from th e bile decreased with longer storage time, The results suggest the fol lowing: 1) that cold ischemia-reperfusion injury of rat liver is media ted by KC-dependent (hepatic microcirculation) and -independent (paren chymal cell function) mechanisms; and 2) that cold storage of rat live r induces functional impairment of BECs.