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 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

A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine tumor and multiple hepatic metastases. Despite optimal treatment with interferon alpha, a somatostatin analog, local therapy with high-intensity focused ultrasound ablation for multiple hepatic metastases, and multiple lines of chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine monotherapy, the tumor progressed. As few chemotherapeutic options were available for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen. Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy. Serial computed tomography scans showed that the primary and metastatic tumors were stable. Thirteen months after beginning targeted therapy, and up to the time of this report, the patient is well without disease progression. We suggest that sorafenib is effective against pancreatic endocrine tumors.
Adult ; Antineoplastic Agents/adverse effects/*therapeutic use ; Benzenesulfonates/adverse effects/*therapeutic use ; Humans ; Liver Neoplasms/drug therapy/pathology/secondary ; Male ; Neuroendocrine Tumors/*diagnosis/drug therapy/pathology ; Pancreatic Neoplasms/*diagnosis/drug therapy/pathology ; Pyridines/adverse effects/*therapeutic use ; Salvage Therapy ; Skin Diseases/chemically induced ; Tomography, X-Ray Computed

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

We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson's disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury.
Acute Disease ; Adrenergic alpha-Antagonists/*adverse effects ; Dysuria/pathology ; Humans ; Liver Diseases/*chemically induced/pathology ; Liver Function Tests ; Male ; Middle Aged ; Prostatic Hyperplasia/drug therapy ; Quinazolines/*adverse effects

OBJECTIVETo evaluate the role of adiponectin in regulating tumor necrosis factor alpha (TNF alpha) production and preventing fulminant autoimmunological damage of hepatocytes following concanavalin A (Con A) injection into mice.

METHODSThree days after recombinant plasmids pAA-neo-mAd were injected into the mice via the tail veins, Con A was injected into the mice. Mice transfected with empty pAA-neo vector served as controls. The serum levels of alanine aminotransferase (ALT), TNF alpha and adiponectin were detected, and histological examination of livers was carried out at different time points after the Con A injection. All results were subjected to statistical analyses.

RESULTSHistological examinations showed that the damage in livers of mice with high serum adiponectin levels was milder than that of the controls. The serum levels of ALT and TNF alpha were both lower than those of the controls (P less than 0.01, respectively). Statistical analyses showed the serum levels of ALT was negatively related to the levels of adiponectin in the sera (r=-0.5034).

CONCLUSIONAdiponectin is effective in protecting hepatocytes from Con A-induced immunological injury. The mechanism of this protective effect may be caused by inhibiting the synthesis and/or release of TNF alpha.

Adiponectin ; blood ; pharmacology ; Alanine Transaminase ; blood ; Animals ; Concanavalin A ; adverse effects ; Female ; Immune System Diseases ; chemically induced ; pathology ; prevention & control ; Liver ; drug effects ; pathology ; Liver Diseases ; pathology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

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

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

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.
Vomiting/chemically induced ; Treatment Outcome ; Survival Analysis ; Neoplasm Recurrence, Local ; Nausea/chemically induced ; Middle Aged ; Male ; Magnetic Resonance Imaging ; Liver Diseases/chemically induced ; Leukopenia/chemically induced ; Humans ; Glioma/*drug therapy/radiotherapy/surgery ; Female ; Drug Administration Schedule ; Dacarbazine/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Combined Modality Therapy ; Brain Neoplasms/*drug therapy/radiotherapy/surgery ; Brain/drug effects/pathology ; Antineoplastic Agents, Alkylating/administration & dosage/adverse effects/therapeutic use ; Adult ; Adolescent ; Administration, Oral

OBJECTIVETo explore the hepatic injury induced by CCl4in SD rat.

METHOD40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination.

RESULT19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group.

CONCLUSIONCCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats.

Animals ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Cysts ; chemically induced ; pathology ; Disease Models, Animal ; Female ; Liver ; pathology ; Liver Cirrhosis ; chemically induced ; pathology ; Liver Diseases ; pathology ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Precancerous Conditions ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley ; Sex Factors