The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.
Alanine Transaminase ; Animals ; Chemical and Drug Induced Liver Injury/drug therapy* ; Dexmedetomidine/pharmacology* ; Galactosamine/toxicity* ; Interleukin-6/blood* ; Lipopolysaccharides/toxicity* ; Liver ; Male ; Mice ; Mice, Inbred BALB C ; Microtubule-Associated Proteins/metabolism* ; Tumor Necrosis Factor-alpha/blood* ; Up-Regulation

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Alanine Transaminase ; blood ; Aldehyde Dehydrogenase ; blood ; Animals ; Antrodia ; chemistry ; Aspartate Aminotransferases ; blood ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Cholestenes ; chemistry ; pharmacology ; therapeutic use ; Cholesterol, VLDL ; blood ; Disease Models, Animal ; Ethanol ; toxicity ; Female ; Fruiting Bodies, Fungal ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Malondialdehyde ; blood ; Mice ; Molecular Structure ; Triglycerides ; blood ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; blood ; metabolism ; Biomarkers ; blood ; Carbon Tetrachloride ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; pathology ; Chromatography, Liquid ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Female ; Liver ; drug effects ; pathology ; Male ; Mass Spectrometry ; Metabolome ; drug effects ; Metabolomics ; Rats ; Rats, Wistar ; Taurocholic Acid ; blood ; Taurodeoxycholic Acid ; analogs & derivatives ; blood

Suicide through naphthalene poisoning is rare. Prolonged hemolytic anemia and hemoglobinuria are typical symptoms of naphthalene poisoning. We report an unusual case of naphthalene poisoning. The decedent was an 87-year-old female who intentionally ingested over 5 g of naphthalene. After more than 5 hours, she was found in a drowsy state. During initial examination, hemoglobin level and urine test results were normal. Aspartate aminotransferase and alanine aminotransferase levels were elevated (854 and 1,197 U/L, respectively). Metabolic acidosis was found on arterial blood gas analysis. The patient was treated conservatively by administration of activated charcoal, calcium gluconate, insulin, and glucose. However, the patient died after 1 day of hospital admission. On autopsy, the liver showed toxic hepatitis with confluent necrosis. Naphthalene concentrations in the blood and gastric contents were 5.4 and 5.8 mg/L, respectively. In conclusion, the decedent ingested naphthalene and died due to liver failure without hemolysis.
Acidosis ; Aged, 80 and over ; Alanine Transaminase ; Anemia, Hemolytic ; Aspartate Aminotransferases ; Autopsy* ; Blood Gas Analysis ; Calcium Gluconate ; Charcoal ; Drug-Induced Liver Injury* ; Female ; Glucose ; Hemoglobinuria ; Hemolysis ; Humans ; Insulin ; Intention ; Liver ; Liver Failure ; Naphthalenes ; Necrosis ; Poisoning* ; Suicide

BACKGROUND/AIMS: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. METHODS: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. RESULTS: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The < or = 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the < or = 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. CONCLUSIONS: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.
Adult ; Aged ; Alanine Transaminase/blood ; Antitubercular Agents/*adverse effects ; Aspartate Aminotransferases/blood ; Biomarkers/blood ; Chemical and Drug Induced Liver Injury/blood/*diagnosis/etiology ; Chi-Square Distribution ; Clinical Enzyme Tests ; Coinfection ; Drug Monitoring/*methods ; Drug Therapy, Combination ; Early Diagnosis ; Female ; Hepatitis/complications/diagnosis ; Humans ; *Liver Function Tests ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Time Factors

Acute graft-versus-host disease (GVHD) following liver transplantation is a rare but fatal complication. The correct diagnosis and management of GVHD after liver transplantation are still major challenges. Herein, we reported successful salvage treatment of acute GVHD by withdrawal of immunosuppression in a patient who presented with fever, skin rashes, and decreased blood cell counts after liver transplantation. This case highlights the need for awareness of drug-induced liver injury if liver function tests are elevated during treatment, especially in patients taking multiple potentially hepatotoxic drugs, such as broad-spectrum antibiotics. When occurs, an artificial liver support system is a useful tool to provide temporary support of liver function for the patient in the event of drug-induced liver injury.
Anti-Bacterial Agents ; Blood Cell Count ; Diagnosis ; Drug-Induced Liver Injury ; Exanthema ; Fever ; Graft vs Host Disease* ; Humans ; Immunosuppression* ; Liver Function Tests ; Liver Transplantation* ; Liver* ; Liver, Artificial

Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.
Acetaminophen/*toxicity ; Animals ; Biomarkers/*blood ; Chemical and Drug Induced Liver Injury/*blood/*diagnosis/pathology ; Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; Hepatocytes/*drug effects ; Inflammation/blood/diagnosis ; Liver Regeneration ; MicroRNAs/*blood/genetics ; Predictive Value of Tests ; Rats ; Time

Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.
Alanine Transaminase/analysis ; Aspartate Aminotransferases/analysis ; Bilirubin/blood ; Chemical and Drug Induced Liver Injury/complications/*diagnosis/pathology ; Duodenal Ulcer/pathology ; Endoscopy, Digestive System ; Female ; Focal Nodular Hyperplasia/complications/*diagnosis/pathology ; Humans ; Liver/enzymology/pathology ; Magnetic Resonance Imaging ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo investigate the protective effects of Yuyin Ruangan Decoction(YRD, traditional Chinese medicine) on experimental hepatic injury in mice.

METHODSThe mice were randomly divided into control group, model group and YRD low, middle and high dose group(n = 11). By ip injection of D-GalN, CCk or thioacetamide (TAA), three models of hepatic injury mice were established to investigate the effects of YRD through detecting the indexes of liver function in serum and, the content of antioxidant system in the hepatic tissue.

RESULTSYRD could decrease the content of alanine aminotransferase (ALT)and aspartate aminotransferase (AST) in serum and that of malonaldehyde (MDA) in the hepatic tissue, upregulate the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hepatic tissue. Furthermore, the above effects were dosedependent in a certain degree. CoNCLUSION: YRD has some protection effects on the model of experimental hepatic injury in mouse.

Alanine Transaminase ; blood ; Animals ; Antioxidants ; metabolism ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; metabolism ; Liver ; drug effects ; enzymology ; Malondialdehyde ; metabolism ; Mice ; Superoxide Dismutase ; metabolism

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/enzymology/*etiology/pathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy/adverse effects ; Plant Preparations/adverse effects ; Prescription Drugs/adverse effects ; Republic of Korea ; Retrospective Studies