OBJECTIVETo investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism.

METHODRats suffering from intrahepatic cholestasis were treated with UDCA. Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyl transpeptidase (gamma-GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na(+) and TCH of bile were measured before and after treatment. In addition, the changes of liver tissue under microscrope were observed and recorded.

RESULTSCompared with the control group, serum ALT, ALP, TBIL, DBIL, gamma-GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na(+) and TCH decreased significantly. Degeneration of hepatocytes, infiltration of inflamed cells and proliferation of small bile ducts in the treatment group were improved under microscope.

CONCLUSIONUDCA may have therapeutic effects on cholestatic hepatitis. The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation.

Animals ; Cholestasis, Intrahepatic ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; therapeutic use

Animals ; Cholestasis, Intrahepatic ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; therapeutic use

Chrysosplenium nudicaule,Tibetan name " Yajima",is recorded as an effective medicine for the treatment of liver and gallbladder diseases by Tibetan Pharmacopoeia published in the past dynasties,but its traditional efficacy has not yet been investigated by means of modern pharmacological research methods. In this paper,the protective effect of extract of C. nudicaule(ECN) on liver injury in mice was observed by using the mice model of intrahepatic cholestasis(IC) induced by α-naphthyl isothiocyanate(ANIT) and the possible mechanism by which ECN work as the therapeutic agent was discussed. The results showed that the serum levels of AST,ALT,ALP,DBIL,TBIL and TBA of the model mice were notably reduced in dose-dependent manner(P<0. 01,P<0. 05). The activity of SOD and GSH-Px in the liver homogenate of mice was increased,while the content of MDA was decreased(P<0. 01,P<0. 05).Pathological examination of liver in mice showed that ECN could improve the pathological changes of liver tissue in mice. The mRNA expression level of genes related to bile acid metabolism were detected by RT-PCR and the results suggested that ECN could significantly increase the expression of genes such as BSEP,FXR and MRP2(P<0. 01,P<0. 05),meanwhile significantly reduce the expression of CYP7 A1(P<0. 01,P<0. 05). These results confirmed the protective effect of ECN on intrahepatic cholestasis-induced liver injury in mice,and indicated that the mechanism may be related to activating FXR and its target genes,reducing bile acid synthesis and increasing bile acid excretion. This study provides a modern pharmacological basis for the clinical application of Yajima in Tibetan medicine.
Animals ; Cholestasis, Intrahepatic ; chemically induced ; drug therapy ; Liver ; Medicine, Tibetan Traditional ; Mice ; Plant Preparations ; pharmacology ; Saxifragaceae ; chemistry

OBJECTIVETo study the therapeutic effect of glucocorticoid on early postoperative cholangiole cholestasis hyperbilirubinemia after liver transplantation.

METHODSThirteen liver transplantation recipients with serum total bilirubin above 171 micromol/L at two weeks to one month postoperatively were enrolled in this study. After exclusion of liver blood supply anomalies, bile duct complications, and acute rejection and establishment of a pathological diagnosis of cholangiole cholestasis by hepatic biopsy, hydrocortisone sodium succinate was infused. The liver functions of the patients were tested at 1 day before and 1 day and 1 week after the treatment. Hepatic biopsy was performed before and 1 week after the treatment to observe histopathological changes.

RESULTSThe serum levels of total bilirubin decreased significantly after the treatment with glucocorticoid. Pathology of the hepatic biopsy demonstrated the resolution of cholangiole cholestasis 1 week after the treatment.

CONCLUSIONGlucocorticoid treatment is effective for early postoperative cholangiole cholestasis hyperbilirubinemia after liver transplantation.

Adult ; Aged ; Cholestasis, Intrahepatic ; complications ; Female ; Humans ; Hydrocortisone ; analogs & derivatives ; therapeutic use ; Hyperbilirubinemia ; drug therapy ; etiology ; Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications ; drug therapy

OBJECTIVETo evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy (ICP) and improving prognosis of perinatal newborn babies.

METHODSSixty in-patients of ICP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treatment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery.

RESULTSAfter treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P < 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P > 0.05).

CONCLUSIONBoth YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.

Adult ; Cholestasis, Intrahepatic ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Phytotherapy ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; S-Adenosylmethionine ; therapeutic use

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.
Rats ; Animals ; 1-Naphthylisothiocyanate/toxicity* ; Powders ; NF-E2-Related Factor 2/genetics* ; Rats, Sprague-Dawley ; Cholestasis, Intrahepatic/drug therapy* ; Liver ; Superoxide Dismutase ; Oxidative Stress

OBJECTIVETo conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that have assessed the effect and safety of ursodeoxycholic acid (UDCA), S-adenosylmethionine (SAMe) and UDCA-SAMe combination therapies for intrahepatic cholestasis of pregnancy (ICP).

METHODSUsing searching protocols and assessment methods recommended by the Cochrane Collaboration to reduce bias in systematic reviews, the databases of Medline, EMBASE, Cochrane Central Register of Controlled Trials (CCRT), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature (CBM) and Wanfang China Online Journals were searched to identify relevant RCTs published from database inception to December 2011.

RESULTSTen RCTs (of 727 pregnant women) were included in the study and represented a low risk for bias. Compared to the patients who received UDCA monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of Cesarean section (odds ratio (OR) =0.45, 95% confidence interval (CI):0.24-0.86), preterm birth (OR=0.36, 95% CI:0.20-0.63), and fetal asphyxia (OR=0.27, 95% CI:0.13-0.56) (all P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of amniotic fluid pollution (OR=0.38, 95% CI:0.14-1.01) or better new bom weight (mean difference (MD) =397.36, 95% CI:-96.17-890.89). Compared to the patients who received SAMe monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of preterm birth (OR=0.39, 95% CI:0.21-0.73), fetal asphyxia (OR=0.23, 95% CI:0.07-0.75), and amniotic fluid pollution (OR=0.41, 95% CI:0.20-0.85) (all, P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of Cesarean section (OR =0.62, 95% CI:0.27-1.44) or better new bom weight (MD =445.95, 95% CI:-143.51-1035.42). Comparison of the two monotherapies (UCDA vs.SAMe) showed no statistical differences in rates of Cesarean section (OR=0.91, 95% CI:0.47-1.78), preterm birth (OR =0.79, 95% CI:0.49-1.38), fetal asphyxia (OR=0.90, 95% CI:0.38-2.12), and amniotic fluid pollution (OR=1.14, 95% CI:0.61-2.13), as well as of new born weight (MD =-62.86, 95% CI:-157.81-32.09). Six studies reported no side effects.None of the included studies reported use of allocation concealment or blinding.

CONCLUSIONUDCA-SAMe combination therapy is better than either UDCA or SAMe monotherapy for improving the outcome of ICP without adverse effects. Large-scale trials with adequate sample sizes and higher quality study design are needed to further confirm the efficiency and safety of UDCA and SAMe for treating ICP.

Cholestasis, Intrahepatic ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; Randomized Controlled Trials as Topic ; S-Adenosylmethionine ; administration & dosage ; adverse effects ; therapeutic use ; Ursodeoxycholic Acid ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the curative effect of Danxiaoling Pill (DXLP), a Chinese herbal preparation, in treating intrahepatic cholestasis in pregnancy (ICP).

METHODSFifty-eight cases of ICP were divided randomly into two groups and treated by DXLP and Composite Yiganling as control respectively with the other identical conventional treatment. The changes of clinical symptoms, related laboratory parameters after treatment and the condition of labor were observed.

RESULTSThe total effective rate in both groups was 100%, but the markedly effective rate in the DXLP treated group was higher than that in control group (P < 0.01). Levels of blood cholyglycine acid (CGA), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, total cholesterol and low density lipoprotein were all decreased in both groups after treatment, but DXL showed a better efficacy in decreasing CGA, ALT and AST than that of Yiganling. Moreover, the amniotic fluid meconium contaminated rate, premature delivery occurrence in the DXLP group were lower than those in the control group, while the weight of newborn baby was higher in the former than in the latter.

CONCLUSIONDXLP could effectively lower the serum bile acid and improve liver function in treating ICP.

Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Cholestasis, Intrahepatic ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycocholic Acid ; blood ; Humans ; Phytotherapy ; Pregnancy ; Pregnancy Complications ; blood ; drug therapy

OBJECTIVETo investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis.

METHODSNinety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR.

RESULTSAt all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (P<0.05). The emodin group had significantly higher mRNA expression of FXR and significantly lower serum levels of TB, DB, ALT, and TBA compared with the model group (P<0.05).

CONCLUSIONSEmodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.

Acute Disease ; Alanine Transaminase ; blood ; Animals ; Cholestasis, Intrahepatic ; drug therapy ; metabolism ; Disease Models, Animal ; Emodin ; pharmacology ; therapeutic use ; Hepatitis ; drug therapy ; metabolism ; Liver ; pathology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; genetics

OBJECTIVETo evaluate the curative effect of Wuling pill (WLP), a traditional Chinese patent medicine, in treating gestation period intrahepatic cholestasis (GPI).

METHODSIn the clinical study, 90 GPI patients were divided into the treated group treated by conventional therapy plus WLP and the control group treated by conventional therapy plus compound Yiganling (YGL) with a ratio of 2:1. Clinical symptoms and accouchement condition were observed. Levels of cholyglycine acid (CGA), total and direct bilirubin (TB and DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected before and after treatment. For the experimental study, GPI rat model was induced by injecting estradiol benzoate to pregnant Wistar rats. The model rats in the treated group were administrated with WLP by gastro-perfusion and those in the control group, were administrated with YGL. Levels of CGA,TB,DB, ALT, AST and ALP in the mother and fetal rats, as well as in the amnionic fluid were determined. Besides, the volume of bile excreted by the mother rats was observed.

RESULTSIn clinical trials, the markedly effective rate in the treated group (47 cases, 78.3% ) was higher than that in the control group (15 cases, 50%, chi2 = 7.17286, P < 0.01). Levels of blood CGA, TB, ALT and AST were all decreased in both groups after treatment, but WLP showed a better efficacy than YGL (P < 0.05) in lowering CGA, ALT and AST. Moreover, the occurrence of meconium contaminated amnionic fluid and premature delivery were lower, while weight and Apgar grade of newborn babies were higher in the treated group than those in the control group. In animal experiment, WLP showed significant effects in decreasing CGA level in amniotic fluid, and in blood of the mother and fetal rats. In addition, it could also decrease the levels of bilirubin, ALT and AST, and promote the bile excretion to reduce CGA concentration in bile. All the above effects showed a dose-dependent pattern.

CONCLUSIONWLP could effectively lower the serum bile acid, improve the hepatic function and better the pregnant outcome in treating GPI.

Adult ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Cholestasis, Intrahepatic ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycocholic Acid ; blood ; Humans ; Phytotherapy ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; Rats ; Rats, Wistar