Attenuation of N-nitrosodiethylamine-induced liver fibrosis by high-molecular-weight fucoidan derived from Cladosiphon okamuranus.
OBJECTIVE
Liver fibrosis is closely associated with the progression of various chronic liver diseases. Fucoidan exhibits different biological properties such as anti-inflammatory, anti-oxidant and anti-fibrotic activities. The aim of this study was to determine whether oral fucoidan administration inhibits N-nitrosodiethylamine (DEN)-induced liver fibrosis.


METHODS
Liver fibrosis was induced in rats by injecting DEN (50 mg/kg). Rats were given 2% of crude fucoidan solution or 2% of high-molecular-weight (HMW) fucoidan solution. They were divided into a crude fucoidan group, an HMW fucoidan group, a DEN alone group, a DEN + crude fucoidan group, a DEN + HMW fucoidan group and a control group.


RESULTS
Liver fibrosis and hepatic hydroxyproline levels were significantly more decreased in the DEN + HMW fucoidan group than in the DEN-alone group. Anti-fibrogenesis was unremarkable in the DEN + crude fucoidan group. Hepatic messenger RNA levels and immunohistochemistry of transforming growth factor beta 1 were markedly increased by DEN. This increase was attenuated by HMW fucoidan. Hepatic chemokine ligand 12 expression was increased by DEN. This increase was suppressed by HMW fucoidan. HMW fucoidan significantly decreased the DEN-induced malondialdehyde levels. Also, fucoidan markedly increased metallothionein expression in the liver. Fucoidan was clearly observed in the liver by immunohistochemical staining in HMW fucoidan-treated rats, while it was faintly stained in the livers of crude fucoidan-treated rats.


CONCLUSIONS
These findings suggest that the HMW fucoidan treatment causes anti-fibrogenesis in DEN-induced liver cirrhosis through the downregulation of transforming growth factor beta 1 and chemokine ligand 12 expressions, and that scavenging lipid peroxidation is well-incorporated in the liver.
Nakazato
Kyoumi
K
School of Health Sciences, Faculty of Medicine, Gunma University, Showa-machi, Maebashi, Japan. nkyoumi@health.gunma-u.ac.jp
Takada
Hisashi
H
Iha
Masahiko
M
Nagamine
Takeaki
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004048:Diethylamines / Q000633:toxicity; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000627:therapeutic use*; D011134:Polysaccharides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012624:Seaweed; D013463:Sulfuric Acid Esters; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004048:Diethylamines; D028321:Plant Preparations; D011134:Polysaccharides; D013463:Sulfuric Acid Esters; C007789:fucoidan; C031406:N-nitrodiethylamine