Chong LW |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=0.619 ------>paper_class3=2 ------>paper_class2=1 ------>vol=13 ------>confirm_bywho=ncchang ------>insert_bywho=m001003 ------>Jurnal_Rank=84.1 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=8 ------>paper_class2Letter=None ------>page2=418 ------>medlineContent= ------>unit=E0100 ------>insert_date=20070424 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=0403-0418 ------>authors_c= ------>score=500 ------>journal_name=Journal of Biomedical Science ------>paper_name=Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats ------>confirm_date=20081128 ------>tch_id=091002 ------>pmid=16604421 ------>page1=403 ------>fullAbstract=Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IKKalpha expression and IkappaBalpha phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats receiving high dose of thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition, real-time PCR analysis indicated that hepatic mRNA expressions of TGF-beta1, alpha-SMA, collagen 1alpha2, TNF-alpha and iNOS genes were attenuated by thalidomide treatment. In conclusion, our results showed that thalidomide inhibited activation of HSC-T6 cells by TNF-alpha and ameliorated liver fibrosis in DMN-intoxicated rats. ------>tmu_sno=None ------>sno=15156 ------>authors2=Hsu YC ------>authors3=Chiu YT ------>authors4=Yang KC ------>authors5=Huang YT ------>authors6= ------>authors6_c= ------>authors=Chong LW ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=4 |