Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis.
The effect of oral taurine supplementation on endotoxin-induced cholestasis was investigated in rat liver. At 12h following lipopolysaccharide (LPS) injection (4mg/kg body weight i.p.) bile flow and bromosulfophthalein (BSP) and taurocholate (TC) excretion were determined in the perfused liver and the expression of the canalicular transporters multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) was analyzed. Injection of LPS induced a significant decrease of bile flow ( 2.2+/-0.2 microl/g liver wet weight/min vs 3.3+/-0.1 microl/g liver wet weight in controls), biliary BSP excretion (10.8+/-2.2 nmol/g/min vs 21.0+/-3.8 nmol/g/min), and biliary TC excretion (114+/-23 nmol/g/min vs 228+/-8 nmol/g/min). These effects were due to transporter retrieval from the canalicular membrane and downregulation of Mrp2 and Bsep expression. In taurine-supplemented rats bile flow was 30% higher than that in untreated rats and the expression of Mrp2 and Bsep protein was increased two- to threefold. In taurine-supplemented rats there was no significant reduction of bile flow or of BSP and TC excretion at 12h following LPS injection. This protective effect of taurine was due to higher Mrp2 and Bsep protein levels compared to nonsupplemented LPS-treated rats, whereas relative Mrp2 retrieval from the canalicular membrane induced by LPS was not significantly different. LPS-induced tumor necrosis factor alpha and interleukin-1beta release were lower in taurine-fed rats; however, downregulation of Mrp2 and Bsep expression by LPS was delayed but not prevented. The data show that oral supplementation of taurine induces Mrp2 and Bsep expression and may prevent LPS-induced cholestasis.
Mühlfeld
Anja
A
Clinic for Gastroenterology, Hepatology and Infectiology, Universitätsklinikum Düsseldorf, Moorenstrasse 5, Germany.
Kubitz
Ralf
R
Dransfeld
Olaf
O
Häussinger
Dieter
D
Wettstein
Matthias
M
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002779:Cholestasis / Q000139:chemically induced / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013654:Taurine / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; C423013:Abcc2 protein, rat; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014409:Tumor Necrosis Factor-alpha; D013654:Taurine