Heterogeneity of rabbit hepatocytes for bile secretion after acinar zone 3 damage induced by bromobenzene. Effect of bilirubin and bile salt infusions.
Anaesthetized rabbits were used to study the effect of bromobenzene-induced hepatic damage to the acinar zone 3 on bile flow, bile salt, sodium secretion as well as bilirubin transport in basal conditions or with infusion of sodium glycodeoxycholate. The bromobenzene-pretreated animals exhibited in basal conditions a lower bile flow (44%) than that of the controls, with a smaller decrease in bile salt output (27%) and sodium output (29%), whereas no modification in endogenous bilirubin excretion was observed. The bile salt independent fraction of secretion (BSIF) was reduced significantly after the toxic lesion both in terms of absolute and relative values. The hepatocytes of the periportal zone were capable of excreting the totality of bilirubin presented to the liver, regardless of the extent of bile flow or the input of bile salts. The infusion of bilirubin at 1.0 mumole/kg/min led to a fall in bile flow which was attributed to the interference of the pigment with the BSIF. The maximal bilirubin excretion was significantly smaller in bromobenzene-pretreated animals than in the controls, which could be due to the incapacity of the intoxicated rabbits to recruit quiescent hepatocytes. When glycodeoxycholate was administered under conditions of maximal bilirubin transport, bile flow increased as did bile salt secretion in both controls and animals with damaged livers. However, clear differences persisted between the two, which could be attributed not only to the volume fraction of necrosis but also to an interference by bilirubin with the hepatic handling of bile salts. Maximal bilirubin excretion increased in a similar way in both groups after glycodeoxycholate administration. It is proposed that glycodeoxycholate infusion facilitates the hepatic depletion of bilirubin, probably by stimulating transport processes.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology*; D001969:Bromobenzenes / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D007263:Infusions, Parenteral; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011817:Rabbits
D001647:Bile Acids and Salts; D001969:Bromobenzenes; D006002:Glycodeoxycholic Acid; C032036:bromobenzene; D001663:Bilirubin