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Hydrophobic Bile Acid (hydrophobic + bile_acid)
Selected AbstractsFibrate for treatment of primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Shinji Iwasaki Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and ,-guanosine 5,-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity. [source] 17,-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell culturesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2006Matteo Ricchi Abstract Background:, Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17,-estradiol (E2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods:, HepG2 cells were exposed for 24 h to DCA (350 µmol/L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 µmol/L), or E2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 µmol/L) or mixtures of E2/DCA or UDCA/DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. Results:, High concentrations of E2 and UDCA prevented DCA-induced decrease in cell viability, increase in enzyme activity and apoptosis evaluated both by 4,,6-diamidino-2-phenylindole dihydrochloride (DAPI) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. In addition, DCA-related apoptosis, assessed by caspase activity, was also prevented by E2 (P < 0.01) in physiological (1,10 nmol/L) doses. The cytoprotective effects of E2 and UDCA was also observed in the WRL-68 cell line. Conclusions:, 17,-Estradiol prevents DCA-induced cell damage in HepG2 and WRL-68 cell lines to an extent comparable to UDCA. The hypothesis that the protective effect of E2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification. [source] Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2007Tzung-Yan Lee The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg,1 YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-, compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg,1 having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and ,8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction. [source] | ||||||||||