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

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

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.
Anti-Bacterial Agents/*adverse effects ; Bilirubin/blood ; Child ; Child, Preschool ; China ; Drug-Induced Liver Injury/blood/*etiology/pathology ; Drugs, Chinese Herbal/*adverse effects ; Female ; Humans ; Liver/pathology ; Male ; Prothrombin Time ; Respiratory Tract Infections/*complications/drug therapy ; Retrospective Studies

Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.
Adult ; Aged ; Alanine Transaminase/blood ; Alkaline Phosphatase/blood ; Aloe/*chemistry/metabolism ; Drug-Induced Liver Injury/*diagnosis/etiology/pathology ; Female ; Humans ; Liver/pathology ; Male ; Middle Aged ; Plant Extracts/*adverse effects/*chemistry ; Splenomegaly/diagnosis ; Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH. METHODS: The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2+/-12.8 years (mean+/-SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were 662.2+/-574.8 U/L, 905.4+/-794.9 U/L, 12.9+/-10.8 mg/dL, 195.8+/-123.3 U/L, and 255.3+/-280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1+/-519.1 vs. 1043.3+/-600.5 U/L), globulin levels (2.7+/-0.4 vs. 3.3+/-0.5 g/dL), and prothrombin time (12.9+/-2.4 vs. 15.2+/-3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7+/-0.9 in the DILI group and 6.5+/-0.9 in the AIH group (P<0.001). CONCLUSIONS: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.
Adult ; Alanine Transaminase/blood ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/blood ; Biopsy ; Drug-Induced Liver Injury/*diagnosis/pathology ; Female ; Globulins/analysis ; Hepatitis, Autoimmune/*diagnosis/pathology ; Herbal Medicine ; Humans ; Jaundice/etiology ; Male ; Middle Aged ; Prothrombin Time

OBJECTIVEChildren with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied. The clinical manifestations and therapeutic approaches were investigated in order to improve its diagnosis and management.

METHODClinical information as well as features and management of 4 inpatients who were suffered from intractable epilepsy with severe liver function impairment induced by VPA since 2006 were collected and analyzed, including age of onset of epilepsy, VPA using age and the time when liver injury occurred, clinical manifestations, auxiliary examinations and management.

RESULTAmong the 4 cases, three were male and one was female. The admitted age ranged from 1 - 9 years and 1 month. The course of disease was 25 d - 6 months. They manifested as refractory epilepsy of epilepsia partialis continua which was difficult to control. After using VPA for 62 d (50 - 76 d), all developed severe impairment of liver synthetic function which was not related to the concentration of VPA. One was diagnosed with Alpers syndrome, two were suspicious of Alpers syndrome, and the other was diagnosed gliocytoma after brain biopsy. VPA was stopped immediately and symptomatic therapies were used. Other than that, intravenous injection of L-carnitine in 3 cases recovered the liver function.

CONCLUSIONVPA-associated severe hepatotoxicity can manifest first as impaired liver synthetic function. Besides alanin transaminase and aspartate transaminase, the liver synthetic function test is more important than monitoring of liver enzymatic functions in monitoring for the hepatotoxicity. Intravenous injection of L-carnitine in early stage showed good treatment effect.

Anticonvulsants ; adverse effects ; Biomarkers ; blood ; Carnitine ; administration & dosage ; therapeutic use ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diffuse Cerebral Sclerosis of Schilder ; chemically induced ; drug therapy ; genetics ; Epilepsy ; drug therapy ; Female ; Humans ; Infant ; Liver ; drug effects ; pathology ; Liver Function Tests ; Male ; Retrospective Studies ; Valproic Acid ; adverse effects

OBJECTIVETo study the protective effects of Isodon lophanthoides var. gerardianus (ILVG) aqueous extract on the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats.

METHODSixty rats were allocated into control group, model group, low, middle and high dosage group and Bifendate group randomly. At the test group, rats received either ILVG aqueous extract (15, 7.5, 3.75 g x kg(-1)) or Bifendate (45 mg x kg(-1)) by gastric perfusion daily for 10 consecutive days. In 1st, 4th, 7th and 10th days, 10% CCl4 (2 mL x kg(-1)) was given to rats by intraperitoneal (ip) injection. The rats were killed 24 h after the last adminiction with drug, the levels of ALT, AST, ALP and total bilirubin in serum were analyzed, the body weight, liver weight, spleen weight and thymus weight of each rat were measured, and the hepatic tissue pathology was observed.

RESULTILVG could decrease the ALT, AST, ALP and T-Bil in serum, restrain the enlargement of liver and the shrinkage of thymus, and reduce the necrosis in pathological observation.

CONCLUSIONILVG aqueous extract possesses the effects of protecting on the acute hepatic injury induced by CCl4 in rats.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Isodon ; chemistry ; Liver ; pathology ; Male ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effect of dl-tetrahydropalmatine(dl-THP) on liver injury induced by carbon tetrachloride (CC4) in mice.

METHODMice were administracted with dl-tetrahydropalmatine ip 20, 40 mg x kg(-1) daily for 9 d respectively, and then actue liver injury model was induced by 0.1% carbon tetrachloride ip 20 mL x kg(-1). The mice were killed 17 h after injection ip of CCl4, serum alanine and aspartate aminotransferase (ALT and AST) activity were measured, and maleic dialdehyde (MDA) and superoxide dismutase(SOD) activity in liver were detected.

RESULTdl-THP significantly reduced the level of serum ALT and AST, inhibited lipoperxidation in liver, while increased SOD activity in liver tissue. Degeneration of hepatocytes was obviously prevented in mice treated with dl-THP, and the liver histological structure was well maintained.

CONCLUSIONdl-THP has inhibitory effects on liver injury induced by CCl4 in mice. The mechanisms may be related with its effects of reducing lipid peroxidation product.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Berberine Alkaloids ; pharmacology ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; etiology ; metabolism ; pathology ; Female ; Lipid Peroxidation ; drug effects ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Protective Agents ; pharmacology ; Random Allocation ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the therapeutic effects and mechanisms of SQDG on carbon tetrachloride-induced chemical liver injury in mice as well as its possible mechanisms. At the same time the pharmacodynamics of SQDG was compared with TGP or ASTs of effective dose.

METHODThe model of carbon tetrachloride-induced chemical liver injury in mice was prepared. The levels of ALT, AST, MDA content, SOD and GSH-Px activities in liver homogenate were assayed by spectrophotometry; Meanwhile, hepatic pathological examination was observed.

RESULTProtective effect of SQDG on carbon tetrachloride-induced chemical liver injury: SQDG was able to significantly decrease serum transaminase levels of chemical liver injury's mice induced by carbon tetrachloride, decreased MDA content and improved the reduced SOD and GSH-px levels in liver homogenate. Furthermore, SQDG also attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cell. Compared with TGP or ASTs of effective dose, SQDG has a better effect on carbon tetrachloride-induced chemical liver injury in mice.

CONCLUSIONSQDG can protect mice injured by carbon tetrachloride-induced chemical.

Alanine Transaminase ; blood ; Animals ; Antioxidants ; isolation & purification ; pharmacology ; Aspartate Aminotransferases ; blood ; Astragalus membranaceus ; chemistry ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; etiology ; metabolism ; pathology ; Drug Combinations ; Glucosides ; isolation & purification ; pharmacology ; Glutathione Peroxidase ; metabolism ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Superoxide Dismutase ; metabolism

AIMTo study the gene expression profiles between the CCl4 injured liver and normal liver in mice, and to screen the differentially expressed genes that relate to liver injury by CCl4 on a large scale using cDNA microarrays.

METHODSMale Kunming strain mice were divided into two groups: one was control group and another was CCl4 injured liver group that was given 0.1% CCI4 oil solution ip at dose of 10 mL x kg(-1) every three days, totally for ten times. Then mRNA in livers of the two groups of mice was extracted, separately, and reversely transcribed to cDNA with the incorporation of different fluorescent-labeled dUTP as the hybridization probes. The mixed probes were hybridized to the cDNA microarrays. The fluorescent signal values were acquired by scanner and analyzed with statistical software.

RESULTSAmong the 14 100 target genes, 379 genes were differentially expressed, in which 163 genes were up-regulated and the other 216 genes were down-regulated. They are closely related to a range of biological functions.

CONCLUSIONUsing the cDNA microarray and experimental animal modeling technique, the differentially expressed genes of CCl4 injured liver in mice on a large scale could be studied. It is useful for further investigation of the injury mechanism of CCl4.

Alanine Transaminase ; blood ; Animals ; Apoptosis Regulatory Proteins ; metabolism ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; etiology ; genetics ; metabolism ; Cytochrome P-450 Enzyme System ; metabolism ; Gene Expression Profiling ; Liver ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 12 ; metabolism ; Mice ; Nuclear Proteins ; metabolism ; Oligonucleotide Array Sequence Analysis ; methods ; Proteins ; metabolism ; Random Allocation