The authors have demonstrated the effect of sodium selenite on the hepatotoxicity due to carbon tetrachloride, by observing the distribution and disaggregation of the pyroninophilic granules in the hepatic cell of the mature male albino mice. Each experimental mouse of the selenite and the selenite plus carbon tetrachloride groups was given a single dose of 4 ug. of sodium selenite per kilogram of body weight and that of the control and the carbon tetrachloride groups was given 0.1 ml. of distilled water alone. Six hours after the first administration of distilled water or sodium selenite, the experimental mice of the carbon tetrachloride and the selenite plus carbon tetrachloride groups were given a single dose of l.0 ml. of carbon tetrachloride per kilogram of body weight and those of the selenite groups were given 0.l ml. of paraffin oil alone. Following the 1ast administration of carbon tetrachloride or paraffin oil, the mice were sacrificed by bleeding (cutting the common carotid artery) at the intervals of 2,3,4,6,8, and 12 hours respectively. Histochemical preparations were stained by the methyl-green and pyronin method and oil red 0 method. The hepatotoxicity due to the administration of carbon tetrachoride was evident in the hepatic cells; the pyroninophilic granlues were partly reduced in volume in the hepatic cells of the centrilobular and the intermediate zones as early as the 3 hour-period, and markedly reduced or disappeared in the centrilobular and some part of the intermediate zones associated with hydropic degeneration as well as in the 6 hour-period. Thereafter marked reduction or dissolution of the pyroninophilic granules was found and extended as the periportal zone at the 12 hour-period. However, the pyroninophilic granules in the hepatic cells of selenite plus carbon tetrachbride group showed no significant changes in the hepatic cells of these zones, compared to the histochemical feature of the granules in the hepatic cells of the control and the selenite groups. Consequently it is suggested that the lipid peroxidative decomposition of the microsomal membranes, which is induced with carbon tetrachloride, would be prevented by a previous administration of sodium selenite.
Animal ; Carbon Tetrachloride Poisoning*/pathology ; Cell Nucleus/drug effects ; Cytoplasm/drug effects ; Cytoplasmic Granules ; Lipids ; Liver/drug effects* ; Liver/pathology ; Male ; Mice ; Selenium/pharmacology* ; Vacuoles/drug effects

Objective: To explore the new mechanism of liver fibrosis through D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced necroptosis as an entry point to inhibit lethal injury. Methods: The carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established. At 6 weeks of fibrosis, the mice were challenged with a lethal dose of D-GalN/LPS, and the normal mice treated with the same treatment were used as the control. The experiment was divided into four groups: control group (Control), acute injury group (D-GalN/LPS), liver fibrosis group (Fib), and liver fibrosis + acute challenge group (Fib + D-GalN/LPS). Quantitative PCR and immunofluorescence were used to analyze the expression of necroptosis key signal molecules RIPK1, RIPK3, MLKL and/or P-MLKL in each group. Normal mice were treated with inhibitors targeting key signaling molecules of necroptosis, and then given an acute challenge. The inhibitory effect of D-GalN/LPS-induced-necroptosis on acute liver injury was evaluated according to the changes in transaminase levels and liver histology. Liver fibrosis spontaneous ablation model was established, and then acute challenge was given. Necroptosis key signal molecules expression was analyzed in liver tissue of mice in each group and compared by immunohistochemistry. The differences between groups were compared with t-test or analysis of variance. Results: Quantitative PCR and immunofluorescence assays result showed that D-GalN/LPS-induced significant upregulation of RIPK1, RIPK3, MLKL and/or P-MLKL. Necroptosis key signal molecules inhibition had significantly reduced D-GalN/LPS-induced liver injury, as manifested by markedly reduced serum ALT and AST levels with improvement in liver histology. Necroptosis signaling molecules expression was significantly inhibited in fibrotic livers even under acute challenge conditions. Additionally, liver fibrosis with gradual attenuation of fibrotic ablation had inhibited D-GalN/LPS-induced necroptosis. Conclusion: Liver fibrosis may protect mice from acute lethal challenge injury by inhibiting D-GalN/LPS-induced necroptosis.
Animals ; Chemical and Drug Induced Liver Injury/pathology* ; Galactosamine/adverse effects* ; Lipopolysaccharides/adverse effects* ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Failure, Acute/chemically induced* ; Mice ; Necroptosis

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line ; Glycyrrhizic Acid ; pharmacology ; Humans ; Lipopolysaccharides ; toxicity ; Liver ; drug effects ; pathology

OBJECTIVETo investigate the pathological changes of major organs in rats that have inhaled methyl ethyl ketone peroxide (MEKP) aerosol and to provide clues to the oxidative damage mechanism of MEKP.

METHODSA total of 100 Sprague-Dawley rats (male-to-female ratio = 1:1) were randomly and equally divided into blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups to inhale clean air, solvent aerosol, or MEKP for 6 h per day, 5 d per week, for 13 weeks. A rat model of subchronic MEKP exposure was established. The clinical manifestations during exposure were recorded. The organ coefficients of the kidney, thymus, and testis were calculated. The histopathological changes of the lung, liver, and testis were observed by HE staining.

RESULTSThe male rats in 1000 mg/m(3) MEKP exposure group had significantly lower organ coefficients of the kidney and testis than those in blank control group, solvent control group, and 50 and 500 mg/m(3) MEKP exposure groups (P < 0.05). The rats in 1000 mg/m(3) MEKP exposure group had a significantly lower organ coefficient of the thymus than those in blank control group and solvent control group (P < 0.05). Some rats in 500 and 1000 mg/m3 MEKP exposure groups had significant damage to the lung, liver, and testis, which demonstrated a worsening trend as the dose increased. Pulmonary hyperinflation, hyperemia, bleeding, interstitial pneumonia, and even lung abscess were seen in the damaged lung. Nuclear enrichment, hepatocyte steatosis, and mild cellular edema in the portal area were seen in the damaged liver. Variable degeneration, necrosis, and dysplasia of spermatogenic cells and significant decrease in sperms in spermatogenic cells were seen in the damaged testis. The female rats in blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups showed no pathological changes in the ovary.

CONCLUSIONInhalation of MEKP aerosol can cause oxidative damage to the liver, lung, kidney, thymus, and testis in rats, particularly to the testis in male rats.

Animals ; Butanones ; administration & dosage ; toxicity ; Female ; Inhalation Exposure ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; pathology ; Thymus Gland ; drug effects ; pathology

OBJECTIVETo study the influence of alcohol on the liver sinusoids endothelial cell (LSEC) fenestrae of rats.

METHODSSetting up the rat model of alcoholic liver disease by orogastric administration of alcohol, then kill the experimental and control groups of rats at the end of 4 weeks, 8 weeks and 12 weeks after alcohol feeding, and also at the end of another 12 weeks after balance foods feeding succeeding with alcohol feeding for 12 weeks. Staining the liver tissue by means of HE method and observing the successive change of LSEC fenestrae by transmission electron microscope.

RESULTSThe normal LSEC was flat with nucleus and organelle arranged regularly. The distal cytoplasm displayed as lamina with many fenestrae, not accompanied by basement membrane (BM) formation under the endothelial cell. At the end of 4 weeks of alcohol feeding, fenestrae decreased at the partial distal LSEC cytoplasm, but no BM developed. At the end of 8 weeks, fenestrae decreased significantly, even disappeared, with the BM developed incompletely under the endothelial cell. Concomitantly, fibroblast with active function developed. At the end of 12 weeks, the changes became more obvious; the complete BM could even be seen. However, this kind of changes was mostly limited in the single or adjoining sinusoids, as well as with little widespread formation of fibrosis. At the end of 12 weeks of stopping alcohol feeding, defenestrae and development of BM attenuated obviously.

CONCLUSIONThe defenestrae and BM of LSEC develop gradually with the chronic alcohol stimulation. Sinusoid capillarization and liver fibrosis even form when significant changes happen. The early change of the limited defenestrae and capillarization may be the basis of alcohol periportal fibrosis formation. This kind of liver fibrosis can be reversible after stopping alcohol feeding.

Animals ; Basement Membrane ; pathology ; Endothelium ; drug effects ; pathology ; Ethanol ; Liver ; blood supply ; pathology ; Liver Cirrhosis, Experimental ; pathology ; Liver Diseases, Alcoholic ; pathology ; Male ; Rats ; Rats, Wistar

Ultrastructural changes were induced in rat liver by the single administration of aflatoxin B1 and G1. These were assessed at intervals of 1, 6, 18, 24 and 48 hours and 1, 4 and 8 weeks. It would appear that administration of aflatoxin B1 induced a marked nucleolar alteration seen from 6 hours after the injection. No significant alterations were noted in animals treated with a small amount of aflatoxin G1, but injection of a larger amount of aflatoxin G1 induced nucleolar alterations similar to aflatoxin Bl treatment. The nucleolar change was characterized by segregation of the granular and fibrillar elements. All three groups showed cytoplasmic changes, such as dilation of rough endoplasmic reticulum with detachment of ribosomes, hyperplasia of smooth endoplasmic reticulum, increased numbers of lipid droplets and microbodies. Autoradiographic studies have shown the absorbtion of both aflatoxin B1 and G1 in parenchymal cells, but aflatoxin Bl was absorbed more intensely than Gl, especially in the nucleus. Autoradiographic findings in electron microscopy showed a marked difference in the size grains between aflatoxin B1 and G1, aflatoxin G1 being 1arger than aflatoxin B1.
Aflatoxins/toxicity* ; Animal ; Autoradiography ; Comparative Study ; Liver/drug effects ; Liver/pathology* ; Male ; Microscopy, Electron ; Rats

Ultrastructural changes were induced in rat liver by the single administration of aflatoxin B1 and G1. These were assessed at intervals of 1, 6, 18, 24 and 48 hours and 1, 4 and 8 weeks. It would appear that administration of aflatoxin B1 induced a marked nucleolar alteration seen from 6 hours after the injection. No significant alterations were noted in animals treated with a small amount of aflatoxin G1, but injection of a larger amount of aflatoxin G1 induced nucleolar alterations similar to aflatoxin Bl treatment. The nucleolar change was characterized by segregation of the granular and fibrillar elements. All three groups showed cytoplasmic changes, such as dilation of rough endoplasmic reticulum with detachment of ribosomes, hyperplasia of smooth endoplasmic reticulum, increased numbers of lipid droplets and microbodies. Autoradiographic studies have shown the absorbtion of both aflatoxin B1 and G1 in parenchymal cells, but aflatoxin Bl was absorbed more intensely than Gl, especially in the nucleus. Autoradiographic findings in electron microscopy showed a marked difference in the size grains between aflatoxin B1 and G1, aflatoxin G1 being 1arger than aflatoxin B1.
Aflatoxins/toxicity* ; Animal ; Autoradiography ; Comparative Study ; Liver/drug effects ; Liver/pathology* ; Male ; Microscopy, Electron ; Rats

Animals ; Hexanes ; blood ; toxicity ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

Carcinoma, Hepatocellular ; pathology ; Cell Transformation, Neoplastic ; drug effects ; Ginsenosides ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Signal Transduction ; drug effects

As the research on the signal transduction pathway of tumor is developing, people has become more aware of the confusion of the signal transduction mechanisms on the tumor cells and their effects on tumor growth, apoptosis, and metastasis. Currently, the research that Chinese medicine and its extract inducing apoptosis and angiogenesis of hepatocellular carcinoma by acting on the signal transduction pathway has made gratifying progress. In this article, we will provide an overview of recent literature about this.
Animals ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Signal Transduction ; drug effects