Urinary benzyl alcohol and hippuric acid in workers exposed to benzyl alcohol during paint-stripping work.

Objective: We aimed to develop a reliable gas chromatography-mass spectrometry (GC-MS) method for detecting urinary benzyl alcohol (BeOH) concentrations and assess the suitability of urinary BeOH as a biomarker for occupational BeOH exposure.

Methods: Thirteen male participants exposed to BeOH during paint-stripping work provided preshift and postshift urine samples, and their personal exposure concentrations were measured. Meanwhile, a control group of 10 nonexposed workers contributed urine samples.

Gender-specific development of experimental autoimmune cholangitis induced by double-stranded RNA.

Here we investigated the gender difference in murine cholangitis resembling human primary biliary cholangitis (PBC) caused by synthetic double-stranded RNA, and underlying hepatic innate immune responses. Female C57Bl/6 mice given repeated injections of polyinosinic-polycytidylic acid (poly I:C) for 24 weeks developed overt cholangitis with positive serum anti-mitochondria-M2 antibody, whereas male mice showed minimal pathological changes without induction in autoantibody. Poly I:C induced hepatic inflammatory cytokines and type-I interferons predominantly in females.

Rifaximin prevents ethanol-induced liver injury in obese KK-A mice through modulation of small intestinal microbiota signature.

Exacerbation of alcoholic hepatitis (AH) with comorbid metabolic syndrome is an emerging clinical problem, where microbiota plays a profound role in the pathogenesis. Here, we investigated the effect of rifaximin (RFX) on liver injury following chronic-binge ethanol (EtOH) administration in KK-A mice, a rodent model of metabolic syndrome. Female, 8-wk-old KK-A mice were fed Lieber-DeCarli diet (5% EtOH) for 10 days, following a single EtOH gavage (4 g/kg body wt).

Glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through modulation of hepatic innate immunity.

Strategies for prevention and treatment of nonalcoholic steatohepatitis remain to be established. We evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-A mice. Male KK-A mice were fed a diet containing 5% glycine for 4 wk, and liver pathology was evaluated.

Sodium 4-phenylbutyric acid prevents murine acetaminophen hepatotoxicity by minimizing endoplasmic reticulum stress.

Background: Acetaminophen (APAP) overdose induces severe oxidative stress followed by hepatocyte apoptosis/necrosis. Previous studies have indicated that endoplasmic reticulum (ER) stress is involved in the cell death process. Therefore, we investigated the effect of the chemical chaperone 4-phenyl butyric acid (PBA) on APAP-induced liver injury in mice.

Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by trans-fatty acid plus fructose.

Excess consumption of trans-fatty acid could increase the risk of non-alcoholic steatohepatitis (NASH); however, treatment targeting trans-fatty acid-induced NASH has not been examined. Here we focused on the influence of trans-fatty acid intake on endoplasmic reticulum (ER) stress in hepatocytes, so we investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA), on trans-fatty acid-caused steatohepatitis using diabetic KK-A(y) mice. Elaidic acid (EA, trans-fatty acid) alone did not cause definitive liver injury.

Innate immune responses involving natural killer and natural killer T cells promote liver regeneration after partial hepatectomy in mice.

To clarify the roles of innate immune cells in liver regeneration, here, we investigated the alteration in regenerative responses after partial hepatectomy (PH) under selective depletion of natural killer (NK) and/or NKT cells. Male, wild-type (WT; C57Bl/6), and CD1d-knockout (KO) mice were injected with anti-NK1.1 or anti-asialo ganglio-N-tetraosylceramide (GM1) antibody and then underwent the 70% PH.

Ursolic acid ameliorates hepatic fibrosis in the rat by specific induction of apoptosis in hepatic stellate cells.

Background & Aims: Specific induction of cell death in activated hepatic stellate cells (HSCs) is a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the cell-killing effect of ursolic acid (UA), a pentacyclic triterpenoid, in activated HSCs both in vitro and in vivo.

Methods: Culture-activated rat HSCs were treated with UA (0-40μM), and the mechanisms of cell death were evaluated.

CD1d-restricted natural killer T cells contribute to hepatic inflammation and fibrogenesis in mice.

Background & Aims: Several lines of evidence suggest that innate immunity plays a key role in hepatic fibrogenesis. To clarify the role of natural killer (NK) T cells in hepatic inflammation and fibrogenesis, we here investigated xenobiotics-induced liver injury and subsequent fibrogenesis in mice lacking mature NKT cells caused by genetic disruption of the CD1d molecule.

Methods: Male CD1d-knockout (KO) and wild-type (WT) mice were given repeated intraperitoneal injections of thioacetamide (TAA, 3times/week; 0.

Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen.

Despite pathophysiological similarities to alcoholic liver disease, susceptibility to acetaminophen hepatotoxicity in metabolic syndrome-related nonalcoholic steatohepatitis (NASH) has not been well elucidated. In this study, therefore, we investigated acetaminophen-induced liver injury in KK-A(y) mice, an animal model of metabolic syndrome. Twelve-week-old male KK-A(y) and C57Bl/6 mice were injected intraperitoneally with 300 or 600 mg/kg acetaminophen, and euthanized 6 h later.

Evaluation and comparison of the antioxidative potency of various carbohydrates using different methods.

A detailed analysis of the antioxidative activity of 12 carbohydrates including chondroitin sulfate, fucoidan, agaro-oligosaccharide, 2-deoxy-scyllo-inosose (DOI), Galbeta1-4DOI, D-glucuronic acid, chitobiose, D-mannosamine, D-galactosamine, D-glucosamine, heparin, and colominic acid was performed using four established methods: 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, superoxide dismutase (SOD) activity assay, and the deoxyribose method. Ascorbic acid and/or catechin were used as positive standards. In the DPPH radical scavenging activity measurements, fucoidan, DOI, and Galbeta1-4DOI showed remarkable levels of activity, although at lower levels than ascorbic acid.

Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-A(y) mice.

Unlabelled: Pathogenesis of metabolic syndrome-related nonalcoholic steatohepatitis (NASH) involves abnormal tissue-repairing responses in the liver. We investigated the effect of pioglitazone, a thiazolidinedione derivative (TZD), on hepatic regenerative responses in obese, diabetic KK-A(y) mice. Male KK-A(y) mice 9 weeks after birth underwent two-thirds partial hepatectomy (PH) after repeated intragastric injections of pioglitazone (25 mg/kg) for 5 days.

Role of apoptosis in acetaminophen hepatotoxicity.

Acetaminophen overdose causes liver injury by mechanisms involving glutathione depletion, oxidative stress and mitochondrial dysfunction. The role of apoptosis in acetaminophen-induced cell killing is still controversial. Here, our aim was to evaluate the mitochondrial permeability transition (MPT) as a key factor in acetaminophen-induced necrotic and apoptotic killing of primary cultured mouse hepatocytes.

Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria.

Disorders in enteric bacteria recognition by intestinal macrophages (Mphi) are strongly correlated with the pathogenesis of chronic colitis; however the precise mechanisms remain unclear. The aim of the current study was to elucidate the roles of Mphi in intestinal inflammation by using an IL-10-deficient (IL-10-/-) mouse colitis model. GM-CSF-induced bone marrow-derived Mphi (GM-Mphi) and M-CSF-induced bone marrow-derived Mphi (M-Mphi) were generated from bone marrow CD11b+ cells.

Breeding severely vitamin B12-deficient mice as model animals.

Newborn mice weaned from mice fed on a B12-deficient diet during pregnancy and lactation were fed on a B12-deficient diet for 90 days after weaning, and the state of B12 deficiency was evaluated. The effect of B12 deficiency on the testicular tissue was also examined. The body weight of the mice fed on a B12-deficient diet for 90 days was slightly lower than that of the control mice administrated CN-B12, and the urinary excretion of methylmalonic acid (MMA) was increased.