metallothionein and Liver-Cirrhosis--Alcoholic

Epidemiology investigation showed that no worker drunk Maotai liquor for nearly 30 years died of hepatic diseases, and no obvious hepatic fibrosis and cirrhosis were found in 99 workers who had drunk Maotai liquor for a long period by epidemiology investigation and needle biopsy. The same finding was detected in rats that were drunk by Maotai liquor continued for 56 days. This study was to investigate the effects of Maotai liquor on the liver and its mechanism of preventing hepatic fibrosis.. After ingestion of Maotai for 56 consecutive days, male SD rats were killed for detecting the levels of metallothionein and malondialdehyde (MDA) in liver tissues. Rat hepatic stellate cells (HSCs) and human HSCs were cultured in vitro to observe the effect of Maotai on HSCs proliferation and collagen synthesis. After ingestion of Maotai for 14 consecutive weeks, the livers of male SD rats were harvested for pathohistological examination.. The level of metallothionein in the liver of Maotai-induced rats increased by 22 folds, whereas the levels of hepatic lipid peroxide and MDA was decreased significantly (P<0.05) in Maotai-induced animals suffering from CCl4. Maotai demonstrated obvious inhibitory effect on proliferation of HSCs and the inhibition was concentration-dependent. Gene expression and protein secretion of collagens could also be inhibited by Maotai. In alcoholic group, typical liver cirrhosis was observed. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of the interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found.. It might be an important mechanism of interfering the progress of hepatic fibrosis that Maotai increases the level of metallothionein in the liver and inhibits the activation of HSCs and the synthesis of collagen proteins.

Topics: Alcoholic Beverages; Animals; Base Sequence; Biopsy, Needle; Cell Division; Cells, Cultured; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hepatocytes; Immunohistochemistry; Liver Cirrhosis, Alcoholic; Male; Metallothionein; Molecular Sequence Data; Polymerase Chain Reaction; Probability; Rats; Rats, Sprague-Dawley; Reference Values; Risk Assessment; Sensitivity and Specificity

To explore the effect on liver and the mechanism of preventing hepatic fibrosis by drinking Kweichow Moutai liquor (Maotai).. (1) After ingested with Maotai for 56 days consecutively, the male SD rats were decollated for detecting metallothioneins and MDA content in liver tissues; (2) Culturing rat hepatic stellate cell (HSC) and human HSC in vitro, observing the effect of Maotai on HSC's proliferation and collagen synthesis; (3) After male SD rats were ingested with Maotai for 14 weeks consecutively, the livers were harvested for pathohistological examination.. (1) Metallothioneins content in the liver of Maotai-induced rats increased by 22 folds, the production of hepatic lipid peroxide, MDA was significantly decreased (P < 0.05) in Maotai-induced animals suffering from CCL4; (2) Maotai demonstrate obvious inhibitory effect against proliferation of HSC, and the inhibition was concentration-dependent. gene expression and protein secretion of collagens could also be inhibited by Maotai; (3) In control alcoholic group, typical cirrhosis of liver was shaped. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found.. It might be an important mechanism of interfering hepatic fibrosis progressing that Maotai induces the increase of metallothioneins content in the liver, inhibits the activation HSC and the synthesis of collagen protein.

Topics: Alcoholic Beverages; Animals; Cells, Cultured; Collagen; Hepatocytes; Humans; Liver Cirrhosis, Alcoholic; Male; Metallothionein; Rats; Rats, Sprague-Dawley

To explore the possible mechanism why drinking Maotai liquor dose not cause hepatic fibrosis.. After being fed with Maotai for 56 days consecutively, the male SD rats were decollated for detecting the biological indexes, and the livers were harvested to examine the liver indexes and the level of hepatic metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen generation were also observed.. Hepatic MT contents were 216.0 ng.g(-1)+/-10.8 ng.g(-1) in the rats of Maotai group and 10.0 ng.g(-1)+/-2.8 ng.g(-1) in the normal control group, which was increased obviously in Maotain group (P<0.05). In the rats with grade CCL(2) poisoning induced by Maotai, hepatic MT content was 304.8 ng.g(-1)+/-12.1 ng.g(-1) whereas in the controls with grade CCL(4) poisoning, it was 126.4 ng.g(-1)+/-4.8 ng.g(-1) (P<0.05). MDA was 102.0 nmol.g(-1)+/-3.4 nmol.g(-1) in Maotai group and 150.8 nmol.g(-1)+/-6.7 nmol.g(-1) in the control group (P<0.05). When both of the groups were suffering from grade CCL(4) poisoning, hepatic MT contents was negatively correlated with MDA (r=-0.8023, n=20, P<0.01). The 570 nmA values of each tube with HSC regeneration at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai were 0.818, 0.742, 0.736, 0.72, 0.682, and 0.604, respectively. From the concentration of 10 g.L(-1), Maotai began to show obvious inhibitory effects against HSC, and the inhibition was concentration-dependent (P<0.05, P<0.01). Type I collagen contents in HSC were 61.4, 59.9, 50.1, 49.2, 48.7, 34.4 microg.g(-1) at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai. At the concentration of 100-200 g.L(-1), Maotai had obvious inhibitory effect against the secretion of type I collagen (P<0.05). Gene expression analysis was conducted on cells with Maotai concentrations of 0, 50, 100g.L(-1) respectively and the ash values of beta-actin gene expression were 0.88, 0.74, and 0.59, respectively,suggesting that at the concentration of 100g.L(-1), Maotai could obviously inhibit gene expression of type I procollagen (P<0.05), but the effect was not obvious at the concentration of 50 g.L(-1) (P>0.05). At the concentration of 10 g.L(-1), HSC growth in vitro inhibition rates were 16.4+/-2.3 in Maotai group and -8.4+/-2.3 in the control group (P<0.05).. Maotai liquor can increase metallothioneins in the liver and inhibit the activation of HSC and the synthesis of collagen in many aspects, which might be the mechanism that Maotai liquor interferes in the hepatic fibrosis.

Topics: Alcoholic Beverages; Animals; Cell Division; Collagen; Hepatocytes; Humans; Liver Cirrhosis, Alcoholic; Male; Metallothionein; Rats; Rats, Sprague-Dawley

Previous studies using metallothionein (MT)-overexpressing transgenic mice have demonstrated that MT protects the liver from oxidative injury induced by alcohol. The mechanism of action of MT is unknown. Because MT primarily binds to zinc under physiological conditions and releases zinc under oxidative stress and zinc is an antioxidant element, it is likely that zinc mediates the protective action of MT. The present study was undertaken to determine the distinct role of zinc in hepatic protection from alcoholic injury. MT I/II-knockout (MT-KO) mice along with their wild-type controls were treated with three gastric doses of ethanol at 5 g/kg at 12-hour intervals. Zinc sulfate was injected intraperitoneally in a dosage of 5 mg/kg/day for 3 days before ethanol treatment. MT concentrations in MT-KO mice were very low and zinc concentrations in MT-KO mice were lower than in wild-type mice. Zinc treatment significantly elevated hepatic MT concentrations only in wild-type mice and increased zinc concentrations in both MT-KO and wild-type mice. Ethanol treatment caused degenerative morphological changes and necrotic appearance in the livers of MT-KO mice. Microvesicular steatosis was the only ethanol-induced change in the liver of wild-type mice. Ethanol treatment decreased hepatic glutathione concentrations and increased hepatic lipid peroxidation, and the concentrations of lipid peroxide products in the wild-type mice were lower than in the MT-KO mice. All of these alcohol-induced toxic responses were significantly suppressed by zinc treatment in both MT-KO and wild-type mouse livers. These results demonstrate that zinc, independent of MT, plays an important role in protection from alcoholic liver injury. However, MT is required to maintain high levels of zinc in the liver, suggesting that the protective action of MT in the liver is likely mediated by zinc.

Topics: Animals; Ethanol; Lipid Peroxidation; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Metallothionein; Mice; Mice, Knockout; Thiobarbituric Acid Reactive Substances; Zinc; Zinc Sulfate

Of 1361 consecutive liver biopsy specimens, 24% contained orcein-positive granules. The highest incidence of positivity was found in biliary disease (90.9%), long before cirrhosis had developed, whereas in chronic non-primarily biliary disease, positive results were almost exclusively in patients with well established cirrhosis. Orcein-positive granules were never found in acute liver disease. These granules were also demonstrated in tumour cells of primary hepatocellular tumours (benign 4 of 4 cases; malignant 9 of 37 cases), while all the secondary tumour deposits were negative. In our view the additional information obtained by this technique warrants its adoption as a routine procedure.

Topics: Carcinoma, Hepatocellular; Coloring Agents; Cytoplasmic Granules; Humans; Liver; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Biliary; Liver Diseases; Liver Neoplasms; Male; Metalloproteins; Metallothionein; Oxazines; Staining and Labeling