title: Protection effect of kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress.
abstract: Prolonged inflammation and oxidative stress are emerging as key causes of pathological wound healing and the development of liver fibrosis. We have investigated the effects of recombinant human kallistatin, produced in Pichia. pastoris, on preventing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Daily administration of kallistatin prevented development of CCl4-induced liver fibrosis, which was evidenced by histological study. In all kallistatin treated rats, activation of hepatic stellate cells (HSC) as assessed by s-smooth muscle actin staining was attenuated, TGF- β1 expression was inhibited, class I serum biomarkers associated with the process of fibrogenesis, such as hyaluronic acid, laminin, and procollagen III, were lowered, compared with that in the model control group. Furthermore, residual hepatic functional reserve was improved by kallistatin treatment. CCl4 induced elevation of malondialdehyde level and reduced superoxide dismutase activity in the liver, while kallistatin reduced these oxidative parameters. We also investigated the effects of kallistatin on rat primary HSC and LX-2, the human HSC cell line. Kallistatin scavenged H2O2-induced ROS in the LX-2 cells, and suppressed the activation of primary HSC. These results suggest recombinant human kallistatin might be a promising drug candidate for therapeutic intervention of liver fibrosis.
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Luli
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Diao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002460:Cell Line; D024061:Collagen Type III / Q000097:blood; D055166:Hepatic Stellate Cells / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006909:Hydroxyproline / Q000737:chemistry; D007249:Inflammation; D007797:Laminin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D010843:Pichia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D015843:Serpins / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D024061:Collagen Type III; D007797:Laminin; D011994:Recombinant Proteins; D015843:Serpins; C051324:kallistatin; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride; D006909:Hydroxyproline