Effects of Japanese herbal medicine Inchin-ko-to on endotoxin-induced cholestasis in the rat.
OBJECTIVE
Inchin-ko-to (ICKT) is an herbal medicine used in Japan to treat jaundice and liver fibrosis.We investigated the effect of oral ICKT supplementation on endotoxin-induced cholestasis in the rat.


METHODS
Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used as a model of sepsis-induced cholestasis. Bile flow, biliary bile salt secretion, biliary glutathione secretion and protein expression of the main hepatobiliary transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by conventional techniques in ICKT treated and non-treated animals.


RESULTS
Injection of LPS induced a significant decrease of bile flow (-24%), biliary bile salts (-40%) and glutathione excretion (-70%) as well as a significant decrease in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially prevented the effects of LPS determining a less intense reduction in bile flow (-10%), a normalization of glutathione excretion as well as a significant increase in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT administration did not modify the effects of LPS on BS secretion or Ntcp protein levels.


CONCLUSIONS
Our data show that oral supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bile salt-independent flow.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Juan Pablo
JP
Arab
Carolina
C
Ramírez
Pablo
P
Muñoz
Margarita
M
Pizarro
Nancy
N
Solís
Arnoldo
A
Riquelme
Marco
M
Arrese
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000627:therapeutic use*; D002779:Cholestasis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D004731:Endotoxins / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D029001:Herbal Medicine; D007564:Japan; D008099:Liver / Q000378:metabolism; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D004365:Drugs, Chinese Herbal; D004731:Endotoxins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C078038:inchinko-to; C071908:sodium-bile acid cotransporter; D005978:Glutathione