Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats.
Reperfusion injury was studied in blood-free perfused livers from fat-loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which occurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during reperfusion in control and alcohol-treated rats, respectively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical PBN/carbon-centered free radical adduct signal was detected in bile of livers from ethanol-treated rats, but not in controls or ethanol-treated rats given GdCl3. Portal pressure increased during the reperfusion period in livers from alcohol-treated rats, although not in controls, and GdCl3 reduced it significantly. Taken together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactivation of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation thereby improving hepatic microcirculation.
Department of Pharmacology, University of North Carolina at Chapel Hill, USA.
Z
Z
Zhong
H D
HD
Connor
R P
RP
Mason
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W
Qu
W
W
Gao
J J
JJ
Lemasters
R G
RG
Thurman
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury
D004041:Dietary Fats; D005609:Free Radicals; D000431:Ethanol; D008315:Malondialdehyde; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; C038958:gadolinium chloride; D010100:Oxygen