title: Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with D-galactosamine-induced acute liver failure.
abstract: Only liver transplantation is currently available therapy for the patients with acute liver failure (ALF). This study was designed to determine whether administration of granulocyte colony-stimulating factor (G-CSF) has therapeutic efficacy in animals with ALF. Female Sprague-Dawley (SD) rats were intraperitoneally injected with a single dose of d-galactosamine (d-GalN, 1.4g/kg) to induce ALF. After 2h, the rats were randomized to receive G-CSF (50μg/kg/day), or saline vehicle injection for 5 days. Rats were observed for survival and assessed for liver injury by serum alanine transaminase (ALT) measurement and histological analysis. CD34+ cells in bone marrow were assessed by flow cytometry. CD34+ cells and Ki-67+ hepatocytes in liver tissue were evaluated by immunohistochemistry. In the ALF model, 5-day survival after d-GalN injection was 33.3% (10/30), while G-CSF administration following d-GalN resulted in 53.3% (16/30) survival (p=0.027). G-CSF treated rats had lower ALT level and less hepatic injury compared with saline vehicle rats. The increases of CD34+ cells in bone marrow and liver tissue and Ki-67+ cells in liver tissue in G-CSF treated rats were higher than those in saline rats. No correlation was observed between CD34+ cells and Ki-67+ hepatocytes in liver tissue in both G-CSF and vehicle rats. It is suggested that G-CSF increases survival rate, decreases liver injury and enhances hepatocyte proliferation in rats with d-GalN-induced ALF possibly through actions including but not limiting to CD34+ cell mobilization, and that G-CSF may be of potential value in treating ALF.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, #277 Yanta West Road, Xi'an 710061, Shaanxi Province, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Kang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lei
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.forename: Guoyu
authors.initials: G
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Sai
authors.initials: S
authors.lastname: Lou
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018952:Antigens, CD34; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005434:Flow Cytometry; D005688:Galactosamine / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D005688:Galactosamine; D000410:Alanine Transaminase