Depletion of Bile Acids and Bilirubin in Dogs with Biliary Obstruction by Plasmaperfusion of Usp-Charcoal-Coated Glass Beads

Abstract

Patients with severe, inoperable cholestasis and intractable pruritus not responding to conventional medical therapy might benefit from a depletion of their bile acid pool by sorbent perfusion since accumulated bile acids are possible responsible for their itching. In vitro, USP-charcoal-coated glass beads removed bile acids from human plasma far better than any other sorbent tested. In order to demonstrate the safety and efficacy and charcoal plasmaperfusion in vivo, five dogs underwent plasmapheresis one week following cholecystectomy and bile duct ligation, and 2.2 +/- 0.2 (mean +/- SD) times their plasma volume was passed over a column containing 400 ml of charcoal-coated glass beads prior to reinfusion. During the procedure the plasma bile acid concentration was reduced by 40.2 +/- 4.0% and the bilirubin level by 48.2 +/- 3.3%. The columns, whose capacity was far from being saturated, retained 1.3 +/- 0.4 times the pre-perfusion plasma pool of bile acids (1.1 +/- 0.2 for bilirubin) suggesting that substantial amounts of bile acids and bilirubin were mobilized from tissue stores. The procedure was well tolerated by the animals and might have promising clinical applications.

Reversibility of Caspase Activation and Its Role during Glycochenodeoxycholate-induced Hepatocyte Apoptosis

“…Cell Culture-Primary hepatocytes were isolated from adult Sprague-Dawley rats by standard liver perfusion procedure (22 1 The abbreviations used are: GCDC, glycochenodeoxycholate; Z-VAD-FMK, benzyloxycarbonyl-VAD-fluoromethyl ketone; RT, reverse transcription; TUNEL, terminal deoxynucleotidyl transferase-collagen-coated dishes (Falcon). Cells at a density of 5.5 ϫ 10 5 were incubated in William's E medium containing 10% fetal bovine serum for varying intervals.…”

“…Bile acids are accumulated in cholestasis (1). The major bile acids include glycocholate and taurocholate, which are crucial for digestion and absorption of fat (2).…”

“…The major bile acids include glycocholate and taurocholate, which are crucial for digestion and absorption of fat (2). Pathophysiologically, ursodeoxycholate and its taurine-conjugated form are protective to hepatocytes by directly suppressing disruption of mitochondrial membrane structure (3), whereas glycochenodeoxycholate (GCDC) 1 is cytotoxic and contributes to hepatocellular injury (4). GCDC may cause hepatocyte damage by both acute necrosis and chronic apoptosis (5,6).…”

The monitoring of progress in apoptosis of liver cells in bile duct-ligated rats

“…Bile acids are accumulated in cholestasis (16) and induce hepatocyte apoptosis and necrosis (17). Bile acids and toxic bile salts like glycochenodeoxycholate (GCDC) cause oxidative damage to cell membranes by stimulating the oxygen free radicals from mitochondria (18).…”

Hemoperfusion through polymer-coated adsorbents for metabolic disorders in liver disease

“…Intolerable itching of this condition may occasionally drive a patient t o suicide. Since the pioneering work of Lauterburg et al (7) using perfusion of plasma through charcoal-coated glass beads, a number of patients have been treated with this method. Outstanding hemocompatibility of our polyhema-resin preparation enabled us t o introduce much simpler hemoperfusion and -in case of necessity -to perform it on the out-patient basis once or twice weekly, similarly to the maintenance dialysis programme in end-stage renal disease.…”