Hepatocytes ; metabolism ; pathology ; Liver Diseases ; genetics ; metabolism ; pathology

To study the mechanism of endotoxin-induced hepatocellular injury in rats, a single dose of endotoxin, 15mg/kg, was injected intraperitoneally with or without dexamethasone pretreatment. Studies included light microscopic, histochemical, and electron microscopic observations with concomitant assay of free acid phosphatase activity of liver homogenateg. The results showed an increase of acid phosphatase activity as early as 30 minutes after the injection of endotoxin, and by light microscopy random focal necrosis of liver cells at 1 hour and fibrin thrombi formation in sinusoids especially within the area of necrosis at 3 hours. However, ultrastructural alteration was noted as early as 5 minutes after the injection of endotoxin characterized by marked dilatation of RER. The degree of necrosis, fibrin thrombus formation, and the elevation of free acid phosphatase activity in the liver homogenates seemed to parallel each other suggesting a possible interrelationship among these phenomena. However, the ultrastructnral changes of the hepatocytes were present far ahead of the appearance of fibrin thrombi formation. Therefore, the causal relationship of the fibrin thrombi to liver cell injury appeared unlikely. Despite the increase of free acid phosphatase activity in liver homogenates, no demonstrable structural disruption of lysosomal membrane was noted. In view of the prominent changes of RER 5 minutes after the endotoxin administration, the primary injurious effect of endotoxin affects the membrane system of all organelles including the lysosomal membrane, leading to the leakage of lysosomal enzymes into the cytoplasmic sap. Dexamethasone pretreatment alleviated necrosis and markedly inhibited fibrin thrombus formation, and the mechanism of this effect is considered to be a stabilizing effect of glucocorticoid upon membrane systems.
Acid Phosphatase/metabolism ; Animal ; Endotoxins* ; Injections, Intraperitoneal ; Liver/enzymology ; Liver/pathology* ; Liver Diseases/chemically induced ; Liver Diseases/metabolism ; Liver Diseases/pathology* ; Male ; Necrosis ; Rats

Adult ; Aged ; Chronic Disease ; Female ; Glucuronidase ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Repressor Proteins

Liver function tests (LFT) are helpful screening tools to detect hepatic dysfunction. LFT are further used to categorize hepatic dysfunctions, to estimate the severity of hepatic disease, and for the follow-up of liver diseases. Since liver performs a variety of functions, no single test is sufficient alone to provide complete estimate of function of liver. Effective interpretation of the hepatic function panel requires knowledge of underlying pathophysiology and the characteristics of panel tests. This review includes a classification of liver diseases, which are commonly detected by routine LFT, a list of liver functions with appropriate tests for each function, and a guide to panel interpretation and further laboratory investigation.
Humans ; Liver/enzymology/metabolism/pathology ; Liver Diseases/blood/*diagnosis ; Liver Function Tests

Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can destroy the structure and function of cells through the damage of biological macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can regulate the proliferation, differentiation and apoptosis of cells through several signaling pathways and participate in fibrogenesis of many organs including hepatic and pulmonary fibrosis. Recent study shows that ROS might have an important effect on the forming of myelofibrosis. Consequently, ROS plays a significant role in the fibrogenesis of tissues and organs. In this review, the relevance between ROS and common tissues and organs fibrosis is summarized.
Animals ; Bone Marrow ; pathology ; Bone Marrow Diseases ; metabolism ; pathology ; Fibrosis ; Humans ; Liver ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; Lung ; pathology ; Pulmonary Fibrosis ; metabolism ; pathology ; Reactive Oxygen Species

Animals ; Isoflavones ; pharmacology ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Rats ; Rats, Wistar ; Reperfusion Injury ; pathology ; prevention & control ; Soybeans ; chemistry

OBJECTIVESTo investigate the relationships between proteasome active center LMP7 subunit and the occurrence and development of alcoholic liver disease.

METHODSEighty male Wistar rats, 170 to 190 g, were randomly divided into two groups: a model group (60 rats) and a control group (20 rats). The model group was given alcoholic intragastric administration plus an olive oil diet. Gavage, twice a day, was used to administer ethanol (30%) in a dose of 4 g/kg/d to the model group rats in the first 4 weeks. In the next 4 weeks, 40% ethanol in a dose of 5 g/kg/d was used, and then in the last 4 weeks, 50% ethanol in a dose of 6 g/kg/d was used. After infusion for 12 weeks, 15 rats (fatty liver group) were sacrificed. Others were divided into two groups; one was the hepatitis group with continued alcohol intragastric administration, the other was the hepatitis control group, receiving equal amounts of normal saline. Both groups were sacrificed after 4 weeks. By HE staining, histological pathology of the rat livers was analyzed. The expression of proteasome LMP7 subunit mRNA was examined by reverse transcription and real-time PCR. The content of LMP7 subunit protein was determined by Western blot.

RESULTSThe LMP7 mRNA level of the fatty liver group was 36% of the control group. The level of the hepatitis control group was 51% of the control group. The level of the hepatitis group was the lowest, which was only 26% of the control group. Western blot results showed that the level of the LMP7 protein content of the control group was 0.50+/-0.01; the level was 0.39+/-0.02 of the fatty liver group; 0.30+/-0.04 of the hepatitis group, and 0.38+/-0.02 of the hepatitis control group. The differences of the LMP7 protein content and mRNA expression correlated with the severity of the pathological alterations of the livers.

CONCLUSIONSThe proteasome LMP7 mRNA expression and protein content decreased in the alcoholic liver group. It may be one of the factors responsible for the decreased activity of proteasome and may play an important role in the pathogenesis of alcoholic liver disease.

Animals ; Liver ; pathology ; Liver Diseases, Alcoholic ; metabolism ; pathology ; Male ; Multienzyme Complexes ; metabolism ; Proteasome Endopeptidase Complex ; Rats ; Rats, Wistar

OBJECTIVETo investigate the expression of K18, Ser-33 and Ser-52 phosphorylated K18 in HBV infected human liver disease and its significance.

METHODSThe expression and localization of K18 and Ser-33, Ser-52 phosphorylated K18 in healthy liver tissue, in liver tissues of patients with post-HBV infection cirrhosis and severe chronic hepatitis were detected by histochemistry.

RESULTSK18, Ser-33 and Ser-52 phosphorylated K18 were expressed in normal liver cells, in liver tissues of cirrhosis patients and severe chronic hepatitis cases. The expression of K18 in the liver cells from the 3 different sources had no significant difference in levels. Ser-33 and Ser-52 phosphorylated K18 were expressed in normal liver cells, in liver tissues of cirrhosis patients chronicity HBV hepatitis and severe chronic hepatitis cases. Ser-33 and Ser-52 located around cytoplasmic membrane, diffused into cytoplasm and expressed at a higher levels in cirrhosis and severe chronic hepatitis.

CONCLUSIONThe expression levels of Ser-33 and Ser-52 phosphorylated K18 increased along with the progression of HBV infected human liver disease. The phosphorylation of K18 could be a marker of progression of HBV infected human liver disease.

Hepatitis B ; metabolism ; Humans ; Immunohistochemistry ; Keratin-18 ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; virology ; Liver Diseases ; metabolism ; pathology ; virology ; Phosphorylation ; Serine ; metabolism

A study conducted 15-year ago showed that only 13.5% of chronic alcoholics developed alcohol-induced liver damage, which misled some people to believe a lack of relationship between the amount of alcohol and the occurrence of liver disease. However, it is true that a significant correlation exists between per capita consumption and the prevalence of cirrhosis. Alcoholic fatty liver is observed in most of chronic alcoholics even though the severity is not uniform. Abstinence remains the cornerstone of therapy for alcoholic liver disease (ALD). There is also consensus for the use of corticosteroids and pentoxifylline in severe alcoholic hepatitis maintaining good nutritional status to treat comorbidities in all forms of ALD, and liver transplantation in the end-stage ALD patients who can stop drinking for 6 months pre-transplantation period. Several clinical trials targeting tumor necrosis factor (TNF-alpha) and reducing oxidative stress have not been successful at this time. There is still a large field of alcohol research to explore in order to go farther in the area of pathophysiology. We need to understand a role of various cytokines and immune cells in the development of ALD to have more treatment tools to cope with ALD.
Alcohols/metabolism ; Cytochrome P-450 CYP2E1/metabolism ; Fatty Liver, Alcoholic/pathology/therapy ; Humans ; Liver Cirrhosis, Alcoholic/pathology/therapy ; Liver Diseases, Alcoholic/*etiology/pathology/therapy ; Oxidative Stress

Adult ; Alanine Transaminase ; metabolism ; Diagnosis, Differential ; Humans ; Liver ; pathology ; Male ; Niemann-Pick Diseases ; pathology