OBJECTIVETo observe the protective effect of ginsenosides (GS) or low dose of glucocorticoid dexamethasone (Dex) alone or combined in managing the liver injury and renal function after transcatheter arterial chemoembolization (TACE).

METHODS120 patients with primary liver carcinoma were randomly divided into four groups (A, B, C, D) with 30 patients in each. Group A was treated with placebo; group B with Dex; group C with GS and group D with Dex plus GS. The changes in liver and renal function after TACE were observe according to the WHO criteria for side effects of anti-cancer drug.

RESULTSCompared with group A, Dex combined with GS was able to reduce the level of TB, ALT/AST, BUN and Child-grade, which significantly protected the liver and kidney (P < 0. 05). However, Dex or GS alone could also improve some parameters of liver and renal function after TACE (P < 0.05).

CONCLUSIONDex combined with GS is effective in managing the liver injury and renal function after transcatheter arterial

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Blood Urea Nitrogen ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Creatinine ; blood ; Dexamethasone ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Ginsenosides ; pharmacology ; therapeutic use ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Iodized Oil ; administration & dosage ; Kidney ; drug effects ; pathology ; physiopathology ; Liver Diseases ; etiology ; pathology ; prevention & control ; Liver Neoplasms ; blood ; therapy ; Male ; Middle Aged ; Prospective Studies ; Topotecan ; administration & dosage

OBJECTIVETo provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.

METHODSTwenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL + UDA group) through oral intake (7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7 th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca(2+)) as well as the bacterio-genetic and endogenous beta-glucuronidase activity for comparing.

RESULTSLevels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment (P < 0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P < 0.05). Moreover, levels of Ca(2+) and endogenous beta-glucuronidase activity got significantly lowered (P < 0.05).

CONCLUSIONCombined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca(2+) and the activity of endogenous beta-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.

Adult ; Bile ; chemistry ; Bile Acids and Salts ; analysis ; Bilirubin ; analysis ; Calcium ; analysis ; Cholagogues and Choleretics ; pharmacology ; Choledochostomy ; Cysteic Acid ; analogs & derivatives ; pharmacology ; Drainage ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gallstones ; metabolism ; Glucuronidase ; analysis ; Glycocholic Acid ; analysis ; Humans ; Male ; Middle Aged ; Taurocholic Acid ; analysis ; Ursodeoxycholic Acid ; analogs & derivatives ; pharmacology

OBJECTIVETo investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice (OJ).

METHODSA total of 180 rats were randomly divided into the sham-operated, model control and treated groups (60 in each group). On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil), direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were determined. And the pathological changes of livers, kidneys and lungs, and protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF-κB), as well as apoptotic indexes of multiple organs were observed, respectively.

RESULTSThe pathological severity scores of multiple organs (including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14, 21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR-4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic indexes in livers (7 and 21 days) in the treated group were significantly lower than those in the model control group (P<0.05 or P<0.01).

CONCLUSIONRadix Astragali Injection exerts protective effects on multiple organs of OJ rats by improving the pathological changes of lung, liver and kidney, decreasing the serum index of hepatic and renal function as well as inhibiting the protein expression of TLR-4 and Bax in the livers and Bax in the kidneys.

Alanine Transaminase ; blood ; Animals ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Immunohistochemistry ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Jaundice, Obstructive ; blood ; drug therapy ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; NF-kappa B ; metabolism ; Organ Specificity ; drug effects ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism ; bcl-2-Associated X Protein ; metabolism ; gamma-Glutamyltransferase ; metabolism

OBJECTIVETo investigate the effect and mechanism of emodin on acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in rats.

METHODAcute cholestatic model in rats was induced by ANIT. Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treatment were set up. Liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transport protein genes mdr1a (multidrug resistance protein 1a), mdr1b (multidrug resistance protein 1b) mdr2 (multidrug resistance protein 2), The expression of P-gp were determined by Western blotting analysis.

RESULTCompared to the model group, Emodin treatment resulted in significant reductions in serum total bilirubin (TBiL), direct bilirubin (DBiL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA) (P < 0.01 or P < 0.05). By examining the liver pathology, it was found that hepatic cellular change and necrosis, inflammatory cell infiltration and bile duct proliferation were notably alleviated in emodin model with ANIT treatment. Analysis of gene expression in livers from emodin-treated cholestatic rats revealed that mdr1a, mdr1b and mdr2 could be up-regulated (P < 0.01 or P < 0.05), expression of P-gp was increased in accordance with its mRNA (P < 0.05).

CONCLUSIONEmodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile-metabolism-related transporter P-gp in the liver to prevent bile acids and other toxic compounds overaccumulation in hepatocytes and hepatic toxicity.

1-Naphthylisothiocyanate ; pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis, Intrahepatic ; chemically induced ; drug therapy ; genetics ; metabolism ; Emodin ; pharmacology ; therapeutic use ; Gene Expression Regulation ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDBlocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation.

METHODSThe orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope.

RESULTSIsotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.

CONCLUSIONSThese results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

4-1BB Ligand ; immunology ; Alanine Transaminase ; metabolism ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; Bilirubin ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Graft Rejection ; immunology ; prevention & control ; Graft Survival ; drug effects ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Liver Transplantation ; adverse effects ; Male ; Rats ; Rats, Inbred Lew

We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-beta1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRalpha, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRalpha and SREBP-1 expression and oxidative stress.
Animals ; Bilirubin/pharmacology/*therapeutic use ; Cell Line, Tumor ; Creatine/blood ; Diabetes Mellitus, Experimental/chemically induced/complications/*pathology ; Diabetic Nephropathies/*drug therapy/etiology ; Disease Models, Animal ; Kidney/pathology ; Lipoproteins, HDL/blood ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase/metabolism ; Orphan Nuclear Receptors/antagonists & inhibitors/genetics/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Streptozocin/toxicity ; Triglycerides/analysis/*biosynthesis/blood