title: Nicotinamide inhibits hepatic fibrosis by suppressing DNA synthesis and enhancing apoptosis of hepatic stellate cells.
abstract: Liver fibrosis and its end-stage disease, cirrhosis, are major worldwide healthcare burdens. In this study, we evaluated the inhibitory effects of nicotinamide (NA) on rat hepatic fibrogenesis and investigated its underlying mechanism. We examined the inhibitory effects of NA in vivo by using F344 rats in a thioacetamide (TAA)-induced fibrogenesis model and assessed the inhibitory effects in vitro by using the rat hepatic stellate cell line THSC-Cl6. In vivo, NA significantly attenuated liver fibrosis in TAA-treated rats as assessed by histological analysis using hematoxylin-eosin and Masson's trichrome staining. In vitro, NA inhibited viability of THSC-Cl6 cells in a dose- and time-dependent manner, suppressed DNA synthesis, and induced apoptosis. Transcription of collagen mRNA and expression of alpha smooth muscle actin (the hallmark of activated hepatic stellate cells) were reduced by NA. Expression of the cell cycle-related proteins cyclin E, cyclin D1, and cyclin-dependent kinase (cdk)4, was reduced by NA treatment, but expression of cyclin A and cdk2 was not. Expression of the cdk inhibitors p16 and p21 was decreased by NA treatment, whereas expression of p27 was increased. It appears that NA inhibits rat hepatic fibrogenesis by suppressing DNA synthesis and enhancing apoptosis of hepatic stellate cells.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, South Korea.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Kyong Bun
authors.initials: KB
authors.lastname: Lee
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D000199:Actins; D003094:Collagen; D004247:DNA; D009536:Niacinamide; D014803:Vitamin B Complex; C498862:Acta2 protein, rat