Intestinal Absorption of Fucoidan Extracted from the Brown Seaweed, Cladosiphon okamuranus

The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro

Interferon-Alpha-Induced Changes in Metallothionein Expression in Liver Biopsies from Patients with Chronic Hepatitis C

An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy ( P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection

Stress-induced Biomarkers in Liver with Non-alcohol Fatty Liver Diseases and Non-alcohol Steatohepatitis

Background& Aims : A comparative study between plasma diagnostic markers and oxidative stressinduced biomarkers localized differently in the liver has not been reported in non-alcohol fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH). Methods : Pathological observations by Hematoxylin and Eosin (HE) staining and immunostaining by specific antibodies against metallothionein (MT)-1/2 and-3,heme oxygenase-1 (HO-1), adiponectin using biopsy samples and plasma diagnostic makers were determined in 37 cases. Results : The MT-1/2,HO-1 and adiponectin levels were all significantly reduced in the liver with NASH compared with NAFLD and control. MT-1/2 was most strongly stained in hepatocytes in the normal and NAFLD liver,while it was significantly reduced in NASH. Adiponectin was stained significantly less at blood vessels in NASH compared with NAFLD and controls. HO-1 was also stained significantly less in the Kupffer cells in NASH compared with NAFLD and controls. MT-3 was stained similarly among the three groups at blood vessel cells. Those biomarkers trended negatively with plasma liver injury biomarkers. Conclusions : The significantly reduced expression of oxidative stress-induced biomarkers in NASH may be associated with the degree of pathological damage. In particular, MT-1/2 appears to exert an important effect in hepatocytes against stress-induced damage in NASH