Search

Background: Biliary secretion of organic anions disturbs the proportional relationship normally pertaining between biliary lipid and bile acid secretion. The mechanism causing this uncoupling of biliary lipid from bile acid secretion is incompletely understood. Impaired micellization of membrane lipids by bile due to biliary contamination with organic anions or lowering of biliary bile acid concentration by enhanced bile acid-independent bile flow has been proposed as causative factors. Recently, we found that hepatic phosphoglycoprotein 3 (pgp3) activity was reduced in pigs during bilirubin-induced uncoupling of biliary lipid from bile acid secretion. Pgp3 is the phosphatidylcholine flippase in the canalicular membrane sustaining biliary phospholipid secretion in pigs. This investigation was undertaken to examine whether bilirubin, dibromosulfophthalein, and bromosulfophthalein uncouple biliary lipid from bile acid secretion by the same mechanism. Methods/Results: Hepatic bile was collected from 24 anesthetized pigs before and during infusion of 0.63 μmol·kg body wt[sup -1] · min[sup -1] intravenous bilirubin, dibromosulfophthalein, or bromosulfophthalein. Bile acid secretion was varied by intraportal cholic acid infusion. Hepatic pgp3 expression was measured by means of Western blot, using C219 antibody. Bilirubin > dibromosulfophthalein > bromosulfophthalein lowered biliary lipid secretion without altering hepatic pgp3 expression, increased bile acid-independent bile flow (bromosulfophthalein > dibromosulfophthalein > bilirubin), and enhanced the capacity of bile to micellize membrane lipids as assayed by means of erythrocyte lysis. Biliary bile acid concentration did not determine biliary lipid secretion. Conclusion: Bilirubin, dibromosulfophthalein, and bromosulfophthalein in bile uncouple biliary lipid from bile acid secretion by inhibiting hepatic pgp3 phosphatidylcholine flippase activity, putatively through diffusing into the pgp3 pore. [ABSTRACT FROM AUTHOR]

Background: Large intravenous bilirubin loads cause loss of hepatic canalicular membrane microvilli and cholestasis. This study examines whether these untoward effects might be due to canalicular membrane injury from cytotoxic bile. Methods: The cytotoxicity of bile was assayed against pig erythrocytes before and throughout 4.5-h intravenous infusion of 170 μg[sup -1] kg body weight of bilirubin in anaesthetized pigs. The capacity to generate canalicular bile flow was tested before and after bilirubin infusion by means of short-term intraportal cholic acid infusion. Results: Bilirubin infusion increased the cytotoxicity of hepatic bile, reduced biliary phospholipid secretion by 90%, and caused cholestasis. Cholic acid infusion before bilirubin also increased the cytotoxicity of bile but increased bile flow and doubled biliary phospholipid output. Conclusion: Large intravenous bilirubin infusions increase the cytotoxicity of bile, suppress biliary phospholipid secretion, and render hepatic canalicular membrane microvilli susceptible to injury from cytotoxic bile so that cholestasis occurs. [ABSTRACT FROM AUTHOR]

Investigates the effects of intravenous bilirubin infusion on biliary phospholipid secretion in pigs. Increase in the biliary cytotoxicity; Alterations in hepatic P-glycoprotein expression; Use of gas chromatography in determining biliary phospholipid fatty acid profile.

Background: Oral intake (60 ml daily) over 12 days in eight healthy volunteers of an immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM (AndoSan™)), reduced the monocyte and granulocyte release of mainly proinflammatory cytokines in vivo, suggesting an anti-inflammatory effect. In this foremost in vivo study, the aim was to examine the effect of such AndoSan™ consumption on the expression of adhesion molecules CD11b, CD11c and CD62L and production of reactive oxygen species (ROS) in leukocytes., Methodology/principal Findings: As shown by flow cytometry, there was a significant increase of CD62L expression on monocytes and granulocytes from before (day 0) compared with 12 days after daily AndoSan™ consumption. However, only minor alterations and no clear trend in the expression of CD11b and CD11c were detected. Intracellular ROS (mainly superoxide ion) were significantly reduced in these cells from days 0 to 12., Conclusions/significance: These results support that oral intake of AndoSan™ exhibits an anti-inflammatory effect in humans in vivo.

Background: Large intravenous bilirubin infusions in bile acid-depleted pigs (BADP) destroy hepatocyte canalicular membrane microvilli (CMV) and cause cholestasis. This study examines whether bilirubin photoconversion product infusions do the same., Methods: The effects of systemic infusion of 135 mumol.kg-1 body weight bilirubin photoconversion products on CMV density and choleretic response to intraportal bile acid infusion were studied in BADP. Furthermore, the effects of 135 mumol.kg-1 b.w. bilirubin infusion, either through an arteriovenous bilirubin photoconversion shunt device (PCD) or intravenously, were measured in PCD-connected BADP., Results: Intravenous bilirubin photoconversion product infusions affected neither the CMV density nor the choleretic response to cholic acid infusion, and neither did bilirubin infusion through the PCD. In contrast, intravenous bilirubin infusion caused canalicular injury and cholestasis in four of six PCD-connected BADP., Conclusion: Bilirubin photoconversion products do not destroy CMV or cause cholestasis in BADP. A bilirubin photoconversion shunt device can confer cholestasis protection to bilirubin-loaded BADP.