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 not completely understood. The aim of the present study was to investigate: 1) whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GadCl) modulates cold ischemia-reperfusion injury of rat liver; and 2) whether cold storage of rat liver involves injury to biliary epithelial cells (BECs). Hepatobiliary function was assessed using an isolated perfused rat liver model. Compared with control livers, in livers subjected to cold storage at 4 degrees C in Euro-Collins solution (EC) for 18 hours or in University of Wisconsin solution (UW) for 48 hours, portal flow was lower and resistance significantly higher, taurocholate (TC) and bromosulfophthalein (BSP) elimination were markedly impaired, bile flow was reduced, and lactate dehydrogenase (LDH) leakage into the perfusate was increased. Pretreatment of rats with GadCl, a selective KC toxicant, abrogated disturbances of the microcirculation in both models, but it did not influence viability and functional parameters of the liver. Most of the parameters studied in livers stored in UW solution for 18 hours were not significantly different from those found in control livers. As to biliary activity of gamma-glutamyl transferase (GGT), as an index of BEC integrity, it was increased with increasing time of cold storage. The reabsorption of glucose from the bile decreased with longer storage time. The results suggest the following: 1) that cold ischemia-reperfusion injury of rat liver is mediated by KC-dependent (hepatic microcirculation) and -independent (parenchymal cell function) mechanisms; and 2) that cold storage of rat liver induces functional impairment of BECs.
Kukan
M
M
Laboratory of Perfused Organs, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
Vajdová
K
K
Horecký
J
J
Nagyová
A
A
Mehendale
H M
HM
Trnovec
T
T
D000818:Animals; D001646:Bile / Q000201:enzymology; D001659:Biliary Tract / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003080:Cold Temperature; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D007728:Kupffer Cells / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008102:Liver Circulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D014022:Tissue Survival / Q000187:drug effects
D005682:Gadolinium; C038958:gadolinium chloride