Protective effects of salidroside against acetaminophen-induced toxicity in mice.

The protective effect of salidroside (SDS) isolated from Rhodiola sachalinensis A. BOR. (Crassulaceae), was investigated in acetaminophen (APAP)-induced hepatic toxicity mouse model in comparison to N-acetylcysteine (NAC). Drug-induced hepatotoxicity was induced by an intraperitoneal (i.p.) injection of 300 mg/kg (sub-lethal dose) of APAP. SDS was given orally to mice at a dose of 50 or 100 mg/kg 2 h before the APAP administration in parallel with NAC. Mice were sacrificed 12 h after the APAP injection to determine aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in serum and glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and caspase-3 expression in liver tissues. SDS significantly protected APAP-induced hepatotoxicity for SDS improved mouse survival rates better than NAC against a lethal dose of APAP and significantly blocked not only APAP-induced increases of AST, ALT, and TNF-alpha but also APAP-induced GSH depletion and MDA accumulation. Histopathological and immunohistochemical analyses also demonstrated that SDS could reduce the appearance of necrosis regions as well as caspase-3 and hypoxia inducible factor-1alpha (HIF-1alpha) expression in liver tissue. Our results indicated that SDS protected liver tissue from the APAP-induced oxidative damage via preventing or alleviating intracellular GSH depletion and oxidation damage, which suggested that SDS would be a potential antidote against APAP-induced hepatotoxicity.

A one-year trial of entecavir treatment in patients with HBeAg-positive chronic hepatitis B.

AIM: To evaluate the efficacy and safety of entecavir (ETV) in hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who had not received a nucleoside analogue and who had failed in lamivudine (LVD) therapy. METHODS: Sixty-one patients were divided into three groups. Forty-two patients who had not received a nucleoside analogue were randomized into two groups: group A (n = 21) received LVD 100 mg/d and group B (n = 21) received ETV 0.5 mg/d. The remaing 19 patients treated with LVD (n = 19), who switched to ETV 1.0 mg/d served as group C. All patients were treated for 48 wk. HBV DNA levels were measured with polimerase-chain-reaction (PCR) analysis. Liver function tests, HBV serology and safety assessments were also conducted. RESULTS: Significantly more patients in group B (52.1% and 71.4%) had undetectable HBV DNA levels than in groups A (35.8% and 38%; P < 0.0001) and C (10.6% and 21.1%, P < 0.0001) at wk 24 and 48, respectively. At wk 48, ALT levels were normalized in more patients in group B (85.7%) than in groups A (76.2%) and C (74%). CONCLUSION: ETV had a significantly higher response rate than LVD in patients with HBeAg-positive CHB who had not previously received a nucleoside analogue; ETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in refractory CHB patients treated with LVD; and ETV is safe in clinical application.

Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model.

AIM: To investigate the therapeutic effect of tetrandrine on liver fibrosis induced by thioacetamide in rats in vivo and in vitro. METHODS: In vitro study: we investigated the effect of tetrandrine on the apoptosis of rat hepatic stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the features of activated cells. In vivo study: hepatic fibrosis was induced in rats by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20 mg/kg for 4 wk compared with intraperitoneal injection of interferon-r. RESULTS: In vitro study: 5, 10 or 25 microg/mL of tetrandrine-induced activation of caspase-3 in t-HSC/Cl-6 cells occurred dose-dependently. In vivo study: tetrandrine treatment as well as interferon-r significantly ameliorated the development of fibrosis as determined by lowered serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil) and the levels of liver hydroxyproline (Hyp), hyaluronic acid (HA), laminin (LN) and also improved histological findings. The effects of tetrandrine at the concentration of 20 mg/kg were better than the other concentration groups. CONCLUSION: Tetrandrine promotes the apoptosis of activated HSCs in vitro. Tetrandrine administration can prevent liver fibrosis and liver damage induced by thioacetamide in rats in vivo, indicating that it might exert a direct effect on rat HSCs.

[Expression of cyclooxygenase-2 and vascular endothelial growth factor in human prostate cancer and its significance].

OBJECTIVE: To evaluate expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in primary prostate cancer and its clinical significance. METHODS: Expressions of COX-2 and VEGF were detected by immunohistochemical assay in tissues of 40 prostate cancer and 10 benign prostatic hyperplasia samples. RESULTS: COX-2 and VEGF levels in prostate cancer were much higher than those in BPH. The degrees of cancer malignancy and invasion positively correlated with the expressions of COX-2 and VEGF. COX-2 level positively correlated with VEGF level. CONCLUSION: The abnormal expression of COX-2 plays an important role in the development of primary prostate cancer. COX-2 and VEGF are good molecular markers of prostate cancer which are hopeful to be used for the assistant diagnosis and the prediction of prognosis of prostate cancer.

[Effects of immunoglobulin on the neuronal expression of IL-1beta and IL-1ra and the neuronal death at hippocampus in rats with convulsion induced by pentylenetetrazol].

OBJECTIVE: To study the effects of immunoglobulin on the neuronal expression of IL-1beta and IL-1ra and the neuronal death at hippocampus in rats with convulsion induced by pentylenetetrazol. METHODS: The epilepsy model was established by injecting intraperitoneally pentylenetetrazol (PTZ) into Wistar rats. Forty-five rats were randomly divided into three groups, normal control group, PTZ plus intravenous immunoglobulin (PTZ-IVIG); PTZ plus normal saline (PTZ-NS). Neuronal death was assessed by light microscopy with the hematoxylin-eosin (HE) staining and with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). IL-1beta and IL-1ra expressions were examined by histochemistry. RESULTS: The ratio of IL-1beta/IL-1ra at hippocampal CA(1) region in PTZ-IVIG group (0.5 +/- 0.1) was significantly lower than that in PTZ-NS group (1.9 +/- 0.5, t = 12.9, P < 0.05). Apoptotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group, compared to PTZ-NS group (t = 27.1, P < 0.05). The numbers of positive cells were 16.4 +/- 3.3/1000 microm(2) in the former and 41.7 +/- 3.5/1000 microm(2) in the latter. Necrotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group (19.0 +/- 2.6/1000 microm(2)), compared to PTZ-NS group (42.3 +/- 4.9/1000 microm(2), t = 20.9, P < 0.05). CONCLUSION: Immunoglobulin could inhibit neuronal death induced by convulsion and its possible mechanism might be the regulation of IL-1 system in neurons.

Morphological and serum hyaluronic acid, laminin and type IV collagen changes in dimethylnitrosamine-induced hepatic fibrosis of rats.

AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN). METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin alpha-SMA staining as well as Sirius-red and HE staining. RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with HE and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 lobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of alpha-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of alpha-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P<0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen. CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-alpha.

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-alpha) 1b on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR,OM and IFN-alpha. Radioimmunoassay was utilized to measure procollagen type III (PCIII) and collagen type IV (CIV). RT-PCR was used to assay the expression of liver transforming growth factor-beta 1 (TGF-beta1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (alpha-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCIII and CIV in BR, OM and IFN-alpha groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-beta1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that alpha-SMA also declined more than that in model group. Serum ALT in IFN-alpha, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-alpha, control and model groups. Serum ALT in OM group was significantly higher than those in BR, IFN-alpha, model, and control groups. CONCLUSION: BR, OM and IFN-alpha can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.