Increased melibiose/rhamnose ratio in bile of rats with acute cholestasis.
OBJECTIVE
Melibiose/rhamnose permeability test is used for noninvasive intestinal mucosa barrier testing. However, the possible escape route of the absorbed saccharides through either intact or impaired blood-biliary barriers has not so far been explored. The objective of the present study was therefore two-fold: First, to describe in detail the biliary pharmacokinetics of melibiose and rhamnose in rats; second, to evaluate the changes of both sugars' pharmacokinetics upon impairment of the blood-biliary barrier by acute extrahepatic cholestasis in rats.


METHODS
Bile duct obstructed (BDO), sham-operated and intact (unoperated) male Wistar rats were administered, 24 h after the appropriate intervention, with a single intravenous dose of melibiose and rhamnose, and a 4-h pharmacokinetic study was performed.


RESULTS
In intact animals, the biliary excretion of melibiose and rhamnose was only 0.06% and 0.4% of the administered dose, respectively, while the urinary excretion accounted for 70.6% and 61.7%, respectively. In BDO animals, the biliary excretion rate of both saccharides, especially that of melibiose, was increased with a consequent 4.4-fold rise of the biliary melibiose/rhamnose ratio, the accepted paracellular permeability indicator. Both, the renal clearance of melibiose and the urinary melibiose/rhamnose ratio remained uninfluenced by cholestasis.


CONCLUSIONS
The present study is the first to describe in detail pharmacokinetic parameters and the biliary excretion of melibiose and rhamnose in healthy and cholestatic rats. The altered melibiose/rhamnose biliary excretion ratio in BDO rats indicates that the test is able to detect the impairment of the blood-biliary barrier in acute extrahepatic cholestasis.
Tomsik
Pavel
P
Department of Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic. tomsikp@lfhk.cuni.cz
Sispera
Ludek
L
Rezacova
Martina
M
Niang
Mohamed
M
Stoklasova
Alena
A
Cerman
Jaroslav
J
Knizek
Jiri
J
Brcakova
Eva
E
Cermanova
Jolana
J
Micuda
Stanislav
S
D000208:Acute Disease; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001648:Bile Canaliculi / Q000378:metabolism*; D002779:Cholestasis / Q000175:diagnosis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003938:Diagnostic Techniques, Digestive System; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008297:Male; D008553:Melibiose / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012210:Rhamnose / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation
D008553:Melibiose; D012210:Rhamnose