Juan Pablo Arab, Carolina Ramírez, Pablo Muñoz, Margarita Pizarro, Nancy Solís, Arnoldo Riquelme, Marco Arrese
Background/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. Material and 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. Conclusion. 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.
Key words. Inchin-ko-to, Cholestasis, Endotoxin, Genipin