Rapid effects of lipopolysaccharides on indocyanine green clearance in rat liver.
BACKGROUND
Lipopolysaccharides (LPSs) are thought to be one of the triggers of organ reactions to sepsis, which causes hepatocellular dysfunction. This dysfunction can be demonstrated by a reduction of organic anion transport. The aim of our study was to assess whether the transport of indocyanine green (ICG) is affected by LPS, and whether Kupffer cells are involved.


METHODS
Single-pass liver perfusion with ICG at a concentration of 57.8 mg/kg/min was performed for 130 min. pH, oxygen tension and perfusion pressure were continuously measured in influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a stable bile flow. LPS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min for 30 min. ICG was determined photometrically in perfusate and bile. To depress the function of Kupffer cells male Wistar rats were treated with GdCl3 24 h in advance. Primary cultured hepatocytes were used for studying the direct effect of LPS on the uptake rate of ICG.


RESULTS
Forty-five minutes after administration of LPS a significant dose-dependent decrease of ICG uptake was seen in animals treated with LPS. Livers of animals pretreated with GdCl3 did not show this decrease. LPS had no direct effect on the uptake of ICG into primary cultured hepatocytes, whereas treatment of these cells with 8-bromo-cGMP resulted in a significant increase of ICG uptake.


CONCLUSIONS
LPS has a rapid dose-dependent effect on the detoxification properties of the liver for ICG. The rapid effect of LPS on ICG uptake in hepatocytes is mediated by Kupffer cells.
Department of Internal Medicine I, University of Regensburg, Germany. SGruene@T-Online.de
S
S
Grüne
M
M
Michl
D
D
Schinharl
M
M
Reng
E
E
Frick
A
A
Holstege
J
J
Schölmerich
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; C016276:8-bromocyclic GMP; D005682:Gadolinium; D006152:Cyclic GMP; D007208:Indocyanine Green; C038958:gadolinium chloride