OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

To assess the neurotoxic effects and redox responses of Aroclor 1254 (A1254) on perinatally exposed rat offspring, A1254 was administered by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Neurobehavioral development, antioxidant enzyme activities, lipid peroxidation (LPO), nitric oxide (NO), and NO synthase (NOS) levels were analyzed in the offspring. Neurobehavioral development analysis revealed delayed appearance of the righting reflex, negative geotaxis, and cliff drop test responses in A1254 exposed group. Developmental A1254 exposure also caused oxidative stress in the brain of PND 22 offspring via reductions in the activity of SOD and GSH-Px, and by promoting a rise in the levels of NO and NOS.
Aging ; metabolism ; Animals ; Cerebral Cortex ; drug effects ; enzymology ; metabolism ; Chlorodiphenyl (54% Chlorine) ; toxicity ; Female ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; enzymology ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; enzymology ; metabolism ; Mice ; Nervous System ; drug effects ; growth & development ; metabolism ; physiopathology ; Nervous System Diseases ; chemically induced ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism

BACKGROUNDDyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications. Previous studies have shown that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO), and NO/endothelial nitric oxide synthase (eNOS) pathway is the key route of NO production. The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester (L-NAME)-induced hypertensive rats by NO/eNOS pathway.

METHODSThirty-six 4-week old Sprague-Dawley (SD) male rats were randomly assigned to 6 groups (n = 6): control group, L-NAME group, control + glibenclamide group, control + NaHS group, L-NAME + NaHS group, and L-NAME + NaHS + glibenclamide group. Measurements were made of plasma triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (CHO), glutamic-pyruvic transaminase (ALT) levels after 5 weeks. Then measurements of NO level and proteins expression of eNOS, P-eNOS, AKT, P-AKT were made in liver tissue.

RESULTSAfter 5 weeks of L-NAME treatment, the blood pressure, plasma TG ((1.22±0.12) mmol/L in L-NAME group vs. (0.68±0.09) mmol/L in control group; P < 0.05) and LDL ((0.54±0.04) mmol/L in L-NAME group vs. (0.28±0.02) mmol/L in control group; P < 0.05) concentration were significantly increased, and the plasma HDL ((0.26±0.02) mmol/L in L-NAME group vs. (0.69±0.07) mmol/L in control group; P < 0.05) concentration significantly decreased. Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS, diminished NO levels ((1.36±0.09) mmol/g protein in L-NAME group vs. (2.34±0.06) mmol/g protein in control group; P < 0.05) and pathological changes of the liver. H2S therapy can markedly decrease the blood pressure ((37.25±4.46) mmHg at the fifth week; P < 0.05), and ameliorate the plasma TG ((0.59±0.06) mmHg), LDL ((0.32±0.04) mmHg), and HDL ((0.46±0.03) mmHg) concentration in L-NAME + NaHS group (all P < 0.05). H2S therapy can also restore eNOS function and NO bioavailability and attenuate the pathological changes in the liver in L-NAME-induced hypertensive rats.

CONCLUSIONH2S protects the L-NAME-induced hypertensive rats against liver injury via NO/ eNOS pathway, therefore decreases the cardiovascular risk.

Animals ; Cardiovascular Diseases ; metabolism ; prevention & control ; Hydrogen Sulfide ; therapeutic use ; Hypertension ; chemically induced ; drug therapy ; Liver ; drug effects ; metabolism ; Male ; NG-Nitroarginine Methyl Ester ; toxicity ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.
Adult ; Benzene/toxicity ; Communicable Diseases/*economics ; Dimethylformamide/toxicity ; Drug-Induced Liver Injury/economics ; Female ; Hematologic Diseases/chemically induced/*economics ; Humans ; Lead/toxicity ; Liver Diseases/*economics ; Male ; Middle Aged ; Occupational Diseases/*economics ; Republic of Korea ; Trichloroethylene/toxicity ; Vinyl Chloride/toxicity ; Workers' Compensation/*economics

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

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Hepatitis B ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; chemically induced ; complications

OBJECTIVETo establish a kidney deficient aging model (KDAM), assess it in antioxidant capacity, HPAT axis function and bone metabolism, and compare with D-galactose aging model.

METHODAging rat model was established by injecting D-galactose solution, meanwhile dexamethasone solution was injected to establish kidney deficient aging model. Then these models were evaluated by serum MDA (malondialdehyde) and GSH-Px (glutathione peroxidase), liver SOD (superoxide dismutase), adrenal, thymus and spleen index, CD4(+), CD8(+), and serum COR (cortisol), BGP (bone Gla-protein), plasma ACTH (adrenocorticotropic hormone) and CRH (corticotropin-releasing hormone).

RESULTCompared with the normal group, the aging model group and the kidney deficient aging group showed significant decrease in liver SOD activity (P < 0.01 on average) and significant increase in serum MDA content (P < 0.01 on average) , and the kidney deficient aging group revealed remarkable decline in plasma ACTH content (P < 0.05). Compared with the normal group and the aging model group, the kidney deficient aging model group's weight, serum GSH-Px decreased (P < 0.01, P < 0.05), adrenal index decreased (P < 0.05, P < 0.01), serum COR decreased (P < 0.05 on average), plasma CRH increased (P < 0.05, P < 0.01), serum BGP content significantly decreased (P < 0.01 on average), value of CD4(+), CD8(+) decreased (P < 0.05, P < 0.01), CD4(+)/CD8(+) increased, but without significant difference.

CONCLUSIONThe kidney deficient aging model shows significant decrease in antioxidant capacity, dysfunction of HPAT axis disorder and abnormal bone metabolism. However, D-galactose aging model only shows a significant difference in antioxidant capacity.

Aging ; drug effects ; physiology ; Animals ; Antioxidants ; metabolism ; Disease Models, Animal ; Galactose ; adverse effects ; Humans ; Kidney ; physiopathology ; Kidney Diseases ; chemically induced ; metabolism ; physiopathology ; Liver ; enzymology ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; 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

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

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.
Anti-Infective Agents/*adverse effects/therapeutic use ; Brain Diseases/*chemically induced/diagnosis ; Hepatic Encephalopathy/*drug therapy/etiology ; Humans ; Liver Cirrhosis/*complications ; Magnetic Resonance Imaging ; Male ; Metronidazole/*adverse effects/therapeutic use ; Middle Aged ; Tomography, X-Ray Computed