Subject(s)
Chromium Radioisotopes , Iron Radioisotopes , Iron-Dextran Complex , Liver Cirrhosis, Alcoholic/complications , Protein-Losing Enteropathies/diagnosis , Serum Albumin , Adult , Aged , Evaluation Studies as Topic , Female , Humans , Liver Cirrhosis, Alcoholic/metabolism , Male , Middle AgedABSTRACT
Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and adenosine diphosphate, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 mumol/hr/100 g for 90 minutes, bile flow is inhibited by 82% and liver adenosine triphosphate (ATP) falls by 60%. The amount of mitochondrial BSP can be computed form the amount of [35S] BSP still bound to mitochondria that are prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP on the one hand and of liver concentration of substrates and BSP on the other gives rise to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the concomitant decrease in bile flow.
Subject(s)
Adenine Nucleotides/metabolism , Adenosine Triphosphate/metabolism , Bile/physiology , Liver/metabolism , Mitochondria, Liver/metabolism , Sulfobromophthalein/pharmacology , Animals , Depression, Chemical , In Vitro Techniques , Liver/drug effects , Male , Mitochondria, Liver/drug effects , Mitochondria, Liver/enzymology , NADP/metabolism , Oxygen Consumption/drug effects , RatsSubject(s)
Citrates/metabolism , Ethanol/pharmacology , Isocitrates/metabolism , Mitochondria, Liver/metabolism , Aconitate Hydratase/metabolism , Animals , Biological Transport/drug effects , Diet , Fatty Liver/enzymology , Fatty Liver/metabolism , In Vitro Techniques , Isocitrate Dehydrogenase/metabolism , Liver/ultrastructure , Magnesium/metabolism , Malates/metabolism , Male , Mitochondria, Liver/enzymology , NAD/metabolism , NADP/metabolism , Oxygen Consumption/drug effects , RatsSubject(s)
Alcoholism/pathology , Liver/pathology , Administration, Oral , Animals , Cytoplasmic Granules , Diet , Endoplasmic Reticulum , Ethanol/administration & dosage , Ethanol/pharmacology , Humans , Lipids/analysis , Liver/drug effects , Male , Microbodies , Microscopy, Electron , Mitochondria, Liver , Mitochondrial Swelling , Rats , Time FactorsSubject(s)
Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/etiology , Liver Cirrhosis/complications , Peptic Ulcer Hemorrhage/complications , Adult , Aged , Alcoholism/complications , Digestive System/diagnostic imaging , Endoscopy , Female , Fiber Optic Technology , Humans , Male , Middle Aged , RadiographyABSTRACT
The effects of drugs which change the bile-salt-independent fraction of bile flow on Na(+)K(a+) and Mg(2+) activated ATPases were studied in membrane fractions rich in bile canaliculi. The administration of phenobarbital caused no induction of these enzymes which could explain the increased bile flow observed in the rat. Rose bengal, in addition to its strong photoxidative inhibition of both ATPases, inhibits the Na(+)K(+) ATPase of rat and rabbit bile canaliculi in the absence of light. A closely related substance, uranine, inhibits neither bile flow nor Na(+)K(+)ATPase. Inhibition of this enzyme by rose bengal may therefore be responsible for the observed effects of this dye on bile flow independent of bile salts.
