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

Alcohols ; Animals ; Disease Models, Animal ; Female ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases, Alcoholic ; metabolism ; pathology ; Proto-Oncogene Proteins c-sis ; biosynthesis ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the antagonism effects of green tea (GT) against microcystin LR (MC-LR) induced hepatotoxicity and nephrotoxicity in mice.

METHODSAll 40 male mice were randomly divided into four groups. Mice in group III and IV were pretreated with green tea for free drink at doses of 2 g/L and 12 g/L prior to MC-LR intoxication, for consecutively 18 days. The toxin treatment mice were administered continually intraperitoneal injections of MC-LR at a dose of 10 microg x kg(-1) x d(-1) bw from day 6th till sacrifice, continually 13 days. Mice were sacrificed and immediately subjected to necropsy, and the body weight, relative organ weight, serum biochemical parameters, antioxidant enzyme levels (SOD and GSH), lipid peroxidation products (MDA) and histopathology were systematically evaluated.

RESULTSMC-LR exposure led to increase the oxidative stress and organ injury was significantly observed through biochemical parameters and microscopic evaluation. However, high dose of GT pretreatment caused a significant elevation in serum GSH and SOD levels, and a decrease of serum MDA level as compared with MC-LR control. The mean values of GSH and SOD activities were separately 467.29 mg/L and 139.22 U/ml in group IV. Subsequently, GT pretreatment obviously diminished the serum ALT, AST and Cr activities. Those pathological damages in liver and kidney, were to a certain extent, lessened in GT pretreatment mice in correlation with the biochemical parameters.

CONCLUSIONGT might elevate antioxidant defense system, clean up free radicals, lessen oxidative damages and protect liver and kidney against MC-LR induced toxicity.

Animals ; Antioxidants ; pharmacology ; Chemical and Drug Induced Liver Injury ; Free Radicals ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Microcystins ; toxicity ; Oxidative Stress ; Tea

OBJECTIVETo explore the effect of Dogwood fruits on tonifying kidney-yang.

METHODThe effect of the water extract of Dogwood fruits on rats model of kidney-yang deficiency with the hydrocortisone was observed.

RESULTThe water extract of Dogwood fruits could make normal the liver weight, and mitigate hepatocyte pathologic changes, increase the heptocellular levels of RNA and hepatin, and decrease the malondialdehyde (MDA) in rats model of kidney-yang deficiency. It could also make the viscera quotiety return to normal way and increase the levels of RNA in the interstitial cells of testicle in rats model of kidney-yang deficiency.

CONCLUSIONWater extract of Dogwood fruits can protect and improve the functions of the liver and testicle in rats model of kidney-yang deficiency.

Animals ; Cornus ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fruit ; chemistry ; Hydrocortisone ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Liver Glycogen ; metabolism ; Male ; Malondialdehyde ; metabolism ; Plants, Medicinal ; chemistry ; RNA ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Testis ; metabolism ; pathology ; Yang Deficiency ; chemically induced ; metabolism ; pathology

BACKGROUND/AIMS: Eukaryotic cell cycle is regulated by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDKs) and their partner cyclins, or by interaction with CDK inhibitors. Thioacetamide (TA) is a weak hepatocarcinogen causing several types of liver damage in a dose dependent manner and ultimately producing malignant transformation. We investigated alterations of expression of cell cycle regulators in the rat liver, involved in G1 entry and progression during TA administration. METHODS: We studied expression patterns of cyclin D1, CDK4, CDK6, p21(CIP1) and p16(INK4a) during daily intraperitoneal injection of low dose TA (50 mg/kg) till 7 day. We used western blot and immunohistochemistry for detection. RESULTS: Expression of cyclin D1, CDK4, CDK6 and p21(CIP1) increased from 6 hour and peaked at 2, 3 day, then decreased next 2 days, and re-increased at 6 day. Cytoplasmo-nuclear translocation of cyclin D1 and p21(CIP1) was evident within 1 day and prominent at 2 and 7 day. Expression of p16(INK4a) increased immediately after TA treatment and remarkably increased from 3 day and progressed till 7 day, showing cytoplasmic location, suggestive of inactive form. Most of in situ immunoreactions occurred at the centrilobular hepatocytes. Concomitant nuclear translocation of p21(CIP1) and cyclin D1, different with p16(INK4a) suggests that p21(CIP1) might be a transporter for nuclear translocation rather than cell cycle inhibitor. CONCLUSIONS: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to cyclin D1, CDK4 and CDK 6, their transporter p21(CIP1), and inactive p16(INK4a), which occur at quiescent hepatocytes, not stem cells.
Animals ; Cell Cycle Proteins/*metabolism ; Cyclin D1/metabolism ; Cyclin-Dependent Kinase 4/metabolism ; Cyclin-Dependent Kinase 6/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; G1 Phase ; Immunohistochemistry ; Liver/*drug effects/enzymology/metabolism ; Liver Diseases/chemically induced/metabolism/pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thioacetamide/*toxicity

This study is to observe the effects of sequoyitol on the expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver diseases. The model of high fat and high sugar diet as well as intraperitoneal injection of small dose of streptozotocin (STZ, 35 mg x kg(-1)) induced diabetic rat liver disease was used. After sequoyitol (50, 25 and 12.5 mg x kg(-1)) was administrated for 6 weeks, the contents of blood glucose (BG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), NO and insulin (Ins) were measured, liver p22 phox and p47 phox mRNA content was determined with real-time PCR and the expression of p22 phox and p47 phox protein was examined by Western blotting. In addition, pathological changes in liver were observed with HE staining. Sequoyitol could reduce the content of fasting blood glucose, ALT, AST, Ins and H2O2, restore insulin sensitive index (ISI) and weight, elevate liver tissue T-AOC and NO content, reduce the NADPH oxidase subunit liver tissue p22 phox and p47 phox mRNA and protein expression, as well as ameliorate liver pathologic lesions. The results showed that sequoyitol can ease the type 2 diabetic rat liver oxidative stress by lowering NADPH oxidase expression.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; Hydrogen Peroxide ; metabolism ; Hypoglycemic Agents ; pharmacology ; Inositol ; analogs & derivatives ; pharmacology ; Insulin ; blood ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; Male ; NADPH Oxidases ; genetics ; metabolism ; Nitric Oxide ; metabolism ; Oxidation-Reduction ; drug effects ; Oxidative Stress ; drug effects ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin

OBJECTIVETo optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine.

METHODSThe liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition.

RESULTSThe ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05).

CONCLUSIONYCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

1-Naphthylisothiocyanate ; toxicity ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Annonaceae ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Body Weight ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Glutathione ; metabolism ; Hepatocytes ; drug effects ; enzymology ; pathology ; Jaundice ; chemically induced ; drug therapy ; pathology ; Liver ; drug effects ; enzymology ; pathology ; Liver Diseases ; drug therapy ; pathology ; Male ; Malondialdehyde ; metabolism ; Organ Size ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity.

METHODSFemale Wistar rats were randomly assigned to control (3 groups, 6 rats in each) and treatment groups (3 groups, 6 rats in each). They were subjected to subcutaneous injections of DM (at doses of 0.003, 0.03, and 0.3 mg/kg bw/d) after 30, 45, and 60 d, respectively.

RESULTSSignificant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase (P≤0.05) of plasma MDA concentrations after 45 d. A significant increase (P≤0.05) in plasma ALT (after 45 and 60 d) and AST (after 60 d) concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages (P≤0.05), especially in the dominance of classes 3 and 4 of obtained comet.

CONCLUSIONDM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.

Animals ; Aspartate Aminotransferases ; metabolism ; Behavior, Animal ; drug effects ; Chemical and Drug Induced Liver Injury ; metabolism ; pathology ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Female ; Insecticides ; administration & dosage ; chemistry ; toxicity ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; pathology ; Liver ; drug effects ; Malondialdehyde ; Molecular Structure ; Nitriles ; administration & dosage ; chemistry ; toxicity ; Organ Size ; Oxidative Stress ; drug effects ; Pyrethrins ; administration & dosage ; chemistry ; toxicity ; Random Allocation ; Rats ; Urea ; blood ; Weight Gain ; drug effects