Hepatobiliary excretion of cysteinyl leukotrienes in three experimental models of acute hepatic injury.
The acute phase response to chemically-induced organ damage involves inflammation and the production of leukotrienes. The liver ordinarily takes up, metabolizes and excretes into bile cysteinyl leukotrienes, but the effect of hepatic injury on these processes is unknown. The hepatic uptake and biliary excretion of LTC4 was studied in male Sprague-Dawley rats after exposure to either streptozotocin (45 mg/kg iv 30 days before experimentation), estradiol-17 beta-valerate (1 mg/kg sc once a week for 3 weeks) or lipopolysaccharide/D-galactosamine (33 micrograms/ kg ip; 300 mg/kg ip at 6 h and 3 h, respectively, before experimentation). Acute liver injury is produced by these treatment paradigms. Glucose concentrations and activities of several marker enzymes in plasma were measured to demonstrate hepatic injury. Biliary excretion of 3H-LTC4 was similar to normal control rats in the three types of acute liver injury. Bile flow rates after 3H-LTC4 injection were reduced in lipopolysaccharide-pretreated rats and increased in estradiol-treated animals. Total biliary excretion of leukotrienes was not altered in any disease group. Thus, these models of acute hepatic injury do not appear to influence the hepatobiliary clearance of leukotrienes.
Medical Sciences Program, Indiana University School of Medicine, Bloomington 47405-4201, USA.
H M
HM
Omar
R A
RA
Sanders
J B
JB
Watkins
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000633:toxicity; D017997:Leukotriene C4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity
D008070:Lipopolysaccharides; D017997:Leukotriene C4; D004958:Estradiol; D013311:Streptozocin