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Protection effect of kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress.

Huang X, Wang X, Lv Y, Xu L, Lin J, Diao Y - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.

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.

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Effects of kallistatin on hepatic hydroxyproline content in CCl4-induced liver fibrosis rats in a dose-dependent manner.The results are shown as the mean±SD (n = 8). ## p<0.01 vs. negative control; *p<0.05 vs. model control group; ** p<0.01 vs. model control group.
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pone-0088498-g002: Effects of kallistatin on hepatic hydroxyproline content in CCl4-induced liver fibrosis rats in a dose-dependent manner.The results are shown as the mean±SD (n = 8). ## p<0.01 vs. negative control; *p<0.05 vs. model control group; ** p<0.01 vs. model control group.

Mentions: The results were further confirmed by analysis of hydroxyproline content in liver. Fibrosis, which is the final result of prolonged liver injury, can be quantified by hydroxyproline analysis and expressed as liver collagen content. Hydroxylation of prolines stabilizes collagen, and increased hydroxyproline content is a marker of fibrosis [17]. The CCl4-treated rats had significantly higher hepatic hydroxyproline content than the oil-injected control rats (Figure 2). Whereas, administration of kallistatin reduced the hepatic hydroxyproline content in CCl4-induced hepatic fibrosis rats in a dose-dependent manner (Figure 2).


Protection effect of kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress.

Huang X, Wang X, Lv Y, Xu L, Lin J, Diao Y - PLoS ONE (2014)

Effects of kallistatin on hepatic hydroxyproline content in CCl4-induced liver fibrosis rats in a dose-dependent manner.The results are shown as the mean±SD (n = 8). ## p<0.01 vs. negative control; *p<0.05 vs. model control group; ** p<0.01 vs. model control group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3928242&req=5

pone-0088498-g002: Effects of kallistatin on hepatic hydroxyproline content in CCl4-induced liver fibrosis rats in a dose-dependent manner.The results are shown as the mean±SD (n = 8). ## p<0.01 vs. negative control; *p<0.05 vs. model control group; ** p<0.01 vs. model control group.
Mentions: The results were further confirmed by analysis of hydroxyproline content in liver. Fibrosis, which is the final result of prolonged liver injury, can be quantified by hydroxyproline analysis and expressed as liver collagen content. Hydroxylation of prolines stabilizes collagen, and increased hydroxyproline content is a marker of fibrosis [17]. The CCl4-treated rats had significantly higher hepatic hydroxyproline content than the oil-injected control rats (Figure 2). Whereas, administration of kallistatin reduced the hepatic hydroxyproline content in CCl4-induced hepatic fibrosis rats in a dose-dependent manner (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.

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.

Show MeSH
Related in: MedlinePlus