Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats.
This study investigated the role of Kupffer cells on survival and graft injury in transplanted fatty livers from rats treated acutely with ethanol. Donor rats were given ethanol (5 g/kg, by mouth) 20 hours before explantation, and liver grafts were preserved in University of Wisconsin cold storage solution for 24 to 42 hours prior to implantation. Blood samples were taken from the inferior vena cava for 3 hours after implantation. During this time, serum aspartate transaminase levels increased gradually from 122 U/L to 597 U/L in control rats, while ethanol treatment elevated values to 2,278 U/L. Gadolinium chloride (20 mg/kg, given intravenously to recipients 24 hours before explantation), a selective inactivator of Kupffer cells, minimized the increase in aspartate transaminase levels significantly. After implantation of grafts cold-stored for 42 hours, survival rates were 88% in control rats but only 33% in ethanol-treated rats. Gadolinium chloride improved survival nearly to control values. Ethanol nearly doubled white blood cell adhesion, an effect also largely blocked by gadolinium chloride. Further, alpha-(4-pyridyl 1-oxid)-N-tert-butylnitrone radical adducts detected in the bile were increased twofold by ethanol treatment. This effect was also reversed by gadolinium chloride. Taken together, these data indicate that survival is poorer and graft injury is greater in fatty livers from ethanol-treated rats. Inactivation of Kupffer cells minimized graft damage, most likely by improving hepatic microcirculation and diminishing lipid peroxidation.
Zhong
Z
Z
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365, USA.
Connor
H
H
Mason
R P
RP
Qu
W
W
Stachlewitz
R F
RF
Gao
W
W
Lemasters
J J
JJ
Thurman
R G
RG
D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood* / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival; D016009:Chi-Square Distribution; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D004347:Drug Interactions; D000431:Ethanol; D005234:Fatty Liver / Q000139:chemically induced / Q000201:enzymology* / Q000601:surgery; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005682:Gadolinium; D006085:Graft Survival; D007728:Kupffer Cells / Q000201:enzymology*; D007962:Leukocytes / Q000187:drug effects; D016031:Liver Transplantation / Q000401:mortality* / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D003287:Contrast Media; D005609:Free Radicals; D000431:Ethanol; D005682:Gadolinium; D001219:Aspartate Aminotransferases; C038958:gadolinium chloride