ABSTRACT
INTRODUCTION: Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence. MATERIAL AND METHODS: Clodronate liposomes were used to deplete macrophages from the liver. Forty-eight rats were equally divided across six study groups: sham operation (sham), liposome treatment and sham operation (liposomes+sham), 1mg/kg LPS i.p. (LPS), liposome treatment and LPS administration (liposomes+LPS), hepatic ischaemia-reperfusion injury with LPS administration (IRI+LPS) and liposome treatment followed by IRI+LPS (liposomes+IRI+LPS). Following 6h of reperfusion, blood, bile, and liver tissue was collected for further analysis. Small bile duct injury was assessed, serum liver tests were performed and bile composition was evaluated. The permeability of the blood-biliary barrier (BBB) was assessed using intravenously administered horseradish peroxidase (HRP). RESULTS: The presence of hepatic macrophages was reduced by 90% in LPS and IRI+LPS groups pre-treated with clodronate liposomes (P<0.001). Severe small bile duct injury was not affected by macrophage depletion, and persisted in the liposomes+IRI+LPS group (50% of animals) and liposomes+LPS group (75% of animals). Likewise, BBB impairment persisted following macrophage depletion. LPS-induced elevation of the chemokine Mcp-1 in bile was not affected by macrophage depletion. CONCLUSIONS: Depletion of hepatic macrophages did not prevent development of biliary injury following LPS or LPS-enhanced IRI. Cholangiocyte activation rather than macrophage activation may underlie this injury. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Subject(s)
Bile Duct Diseases/immunology , Bile Ducts/pathology , Epithelial Cells/immunology , Macrophages/immunology , Reperfusion Injury/immunology , Animals , Bile/drug effects , Bile/metabolism , Bile Ducts/cytology , Bile Ducts/immunology , Chemokine CCL2/immunology , Chemokine CCL2/metabolism , Clodronic Acid/pharmacology , Disease Models, Animal , Epithelial Cells/drug effects , Humans , Lipopolysaccharides/toxicity , Liposomes , Liver/blood supply , Liver/cytology , Macrophages/drug effects , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury/complicationsSubject(s)
Fertility/drug effects , Pesticides/pharmacology , Animals , Birds , Cattle , DDT/pharmacology , Estrogens/metabolism , Female , Male , Mice , Poultry , RabbitsABSTRACT
In two experiments, hens received 200 (group I) or 100 ppm of DDT per day and per kg of live weight (group II), for 17 or 10 days resp. The eggs of experimental hens were collected, and a 3 or 6 day collection of eggs was used for preparing a sample of pooled egg yolks; one part of this sample was used for preparation of a 25% egg yolk-citrate diluent, the other for DDT determination. The egg yolks of experimentally poisoned hens contained 12 to 957 ppm of DDT (egg yolks of controls 1-4 ppm) in consecutive collection samples. However, the survival time and survival indexes of bull semen (90 ejaculates) preserved at 3 degrees C and 46 degrees C in yolk citrate diluent containing DDT poluted egg yolk did not differ from those preserved in control diluter.
