We performed DNA microarray analysis on the white blood cells (WBCs) of rats housed on solid and grid cage flooring. The expression levels of 50 genes were found to increase more than 2-fold in the WBCs on grid cage flooring, including many genes encoding proteins involved in inflammatory or immune ...

Rats subjected to bilateral common carotid artery (CCA) occlusion or 2-vessel occlusion (2VO) have been used as animal models of subcortical ischemic vascular dementia. However, this model possesses an inherent limitation in that cerebral blood flow (CBF) drops too sharply and substantially after ligation of CCAs. To circumvent such hypoxic-ischemic ...

Endosulfan is an important hepatotoxic agent that generates free oxygen radicals in liver. With the widespread use of endosulfan in agriculture, human beings are most likely to be exposed to it by eating food contaminated with endosulfan, exposure to its low levels by skin contact with contaminated soil, smoking cigarettes ...

Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were ...

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ...

The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats ...

Since selenium supplements have been shown to undergo biotransformation in the gut, probiotic treatment in combination with selenium supplements may change selenium disposition. We investigated the metabolism of L: -selenomethionine (SeMet) and selenite by probiotic bacteria in vitro and the disposition of selenium after probiotic treatment followed by oral dosing ...

The purpose of this work was to evaluate if the fat liver accumulation interferes with intracellular calcium fluxes and the liver glycogenolytic response to a calcium-mobilizing α(1)-adrenergic agonist, phenylephrine. The animal model of monosodium l-glutamate (MSG)-induced obesity was used. The adult rats develop obesity and steatosis. Calcium fluxes were evaluated ...

BACKGROUND: Cold storage in any of the commonly used preservation solutions is not always adequate for donation after cardiac death (DCD) liver grafts due to prolonged warm ischemic time. In this study, we used a third-generation perfluorocarbon (PFC), Oxycyte, for DCD liver graft preservation in a rat model. MATERIALS AND ...

The purpose of this study was to investigate the effect of chronic cysteamine (CS) supplementation on rat metabolism. Rats received biweekly intragastric administration of either CS-HCl at 250 mg/kg body weight or saline (control) for four weeks. Twenty-four-hour urine and blood serum samples after the last CS treatment were analyzed ...

PURPOSE: Romiplostim, a treatment for adults with immune thrombocytopenia (ITP), is a novel thrombopoietin mimetic agent with a similar mechanism of action as thrombopoietin with no sequence homology. Structurally, it is a peptibody containing thrombopoietin mimetic peptides and the Fc portion of human IgG(1). We investigated romiplostim pharmacokinetics in rodents ...

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of ...

Magnesium (Mg) deficiency is well known to affect metabolism of some trace minerals. We investigated the effect of Mg deficiency on hepatic concentration of various minerals in rats. Twelve 5-week-old male rats were divided into the groups given a control diet and an Mg-deficient diet. After 4 weeks, liver sample was ...

AIM: To assess the diagnostic accuracy of a new reconstruction technique for gradient-recalled-echo magnetic resonance (MR) sequences that provides a full decomposition of the water and fat content inside a voxel for nonalcoholic fatty liver disease (NAFLD) in rats. MATERIAL AND METHODS: Rats were randomized into two groups. A control ...

We examined age-related changes in the protein expression of carbonic anhydrase III (CAIII) in livers of Long-Evans with a cinnamon-like color (LEC) rats using an agouti color (LEA) rats as controls. The levels of the protein of CAIII in the liver of LEC male rats increased before 20 weeks of ...

Objectives  The importance of drug lipophilicity on absorption from the liver surface was examined in rats using paraben derivatives, antipyrine, Sudan III, and Sudan blue. Methods  The log partition coefficient (PC) of n-octanol/water ranged from -1.39 to 4.62. The compounds were applied to the rat liver surface using a cylindrical ...

Levels of urinary dialkylphosphates (DAPs) are currently used as a biomarker of human exposure to organophosphorus insecticides (OPs). It is known that OPs degrade on food commodities to DAPs at levels that approach or exceed those of the parent OP. However, little has been reported on the extent of DAP ...

2,4,6-Triphenyldioxane-1,3 (TPD) is a highly effective species-specific inducer of CYP2В in rats. Several analogs of TPD were synthesized to verify a hypothesis that minor changes in the inducer structure can cause changes in induction abilities (R=H, cisTPD and transTPD; R=N(CH(3))(2), transpDMA; R=NO(2), transpNO(2); R=F, transpF; R=OCH(3), transpMeO). Five of six ...

The present study assessed and compared the oxidative and reductive biotransformation of brominated flame retardants, including established polybrominated diphenyl ethers (PBDEs) and emerging decabromodiphenyl ethane (DBDPE) using an in vitro system based on liver microsomes in liver microsomes from various arctic marine-feeding mammals: polar bear (Ursus maritimus), beluga whale (Delphinapterus ...

Purpose: To correlate spin-lattice relaxation time in the rotating frame (T1ρ) measurements with degree of liver fibrosis in a rat model. Materials and Methods: The protocols and procedures were approved by the local Animal Experimentation Ethics Committee. Liver fibrosis was induced with biliary duct ligation (BDL). Two studies, 1 month ...

Salvia miltiorrhiza (Danshen) is a famous Traditional Chinese medicine used widely in the treatment of cardiovascular and cerebrovascular diseases. This study explored the effects of Danshen capsules commonly used in clinical practice on the liver CYP3A activity in humans and rats. The effects of Danshen extract on liver CYP3A activity ...

Objective: The pharmacokinetic properties of three newly synthesized retinoid X receptor (RXR) agonists were evaluated in rats to elucidate the structural factor influencing their pharmacokinetic properties. Material and methods: Three RXR agonists possessing a common 6-[N-ethyl-N-(3-alkoxy-4-isopropylphenyl)amino]nicotinic acid skeleton and side chain structures that are slightly different from each other were ...

Objectives  Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post-menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)(2) on body weight gain, intra-abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized ...

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic ...

The biotransformation of honokiol, a major constituent of the bark of Magnolia officinalis, was investigated in rat and human livers. When isolated, rat livers were perfused with 10 µM honokiol and two metabolites, namely hydroxylated honokiol conjugated with glucuronic and sulfuric acid (M1) and honokiol monoglucuronide (M2), were quantified in bile ...

Alcoholic fatty liver disease (AFLD) is the result of an excessive or chronic consumption of alcohol. Nine male Wistar rats per group were randomly assigned to one of the following drinking treatments: a 20% (w/w) alcohol solution (ALC); a 20% (w/w) alcohol solution cotreated with 0.25 g silymarin/kg BW/day; or ...

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop and is reported to protect against various diseases such as cancer. To investigate the effect of the ethanolic extract of adlay bran (ABE) on drug-metabolizing enzymes and glutathione-related antioxidant enzymes in rats, three groups of eight male Sprague-Dawley rats ...

We describe the preclinical and clinical pharmacokinetic profiles of FK3453 [6-(2-amino-4-phenylpyrimidin-5-yl)-2-isopropylpyridazin-3(2H)-one] and the mechanism responsible for poor oral exposure of FK3453 in humans. FK3453 showed favourable profiles in preclinical pharmacokinetic studies, including satisfactory absolute bioavailability and total body clearance in animals (30.5%-41.4%, 54.7%-68.2%, and 71.3%-93.4% and 10.8-17.6, 1.9-17.1, and 5.0 mL/min/kg ...

AIM OF THE STUDY: Tripterygium Wilfordii Multiglycoside (GTW), an authorized Chinese patent drug, is used for treatment of rheumatoid arthritis and other immune disease. This study was to determine whether GTW induced different toxic reactions in Adjuvant Arthritis rats (AA rats) compared to those in normal rats. MATERIALS AND METHODS: ...

Non-alcoholic steatohepatitis (NASH) is becoming a prevalent disease in developing countries with no effective therapy. Isoflavones such as genistein have been shown to prevent NASH in a rat model, but the effects of neonatal exposure to genistein on lipid metabolism have been rarely studied. In the present study, three doses ...

Micafungin (MCFG) is a novel echinocandin-class antifungal agent that extensively undergoes metabolic removal in the liver. In the present study, the influence of decreased blood volume on pharmacokinetic disposition of MCFG was examined using a rat model prepared by phlebotomy. In phlebotomized rats, hematocrit level and plasma albumin concentration were ...

Cytochrome P450 (CYP)-mediated drug interactions caused by Kampo medicine have not been investigated sufficiently. The current study was conducted to reveal the effect of anchusan, a commonly used Kampo formula for gastrointestinal disease, on CYP3A-mediated drug metabolism in rats. The pharmacokinetics of midazolam (MDZ) was investigated after the single or ...

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. ...

Although recent studies have demonstrated the in vitro hepatic differentiation potential of mesenchymal stem cells (MSCs), the evidence supporting the in vivo engraftment of MSCs, hepatic differentiation and improvement of hepatic function is still lacking. We investigated in vivo hepatic differentiation potential and therapeutic effect of cord blood derived-MSCs (CBMSCs) transplantation in a ...

The human placenta is an organ for fetus development and abundant reservoir of various bioactive molecules. Interest to human placenta extract (hPE) is growing, and application with trial of hPE is widening in oriental medicine including in liver diseases. However, underlying mechanisms for therapeutic effects are still unclear. Here, we ...

Setileuton (4-(4-fluorophenyl)-7-[({5-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-1-benzopyran-2-one) is a selective inhibitor of the 5-lipoxygenase enzyme, which is under investigation for the treatment of asthma and atherosclerosis. During the development of setileuton, a metabolite (M5) was identified in incubations with rat, dog, and human liver microsomes which represented the addition of 18 Daltons to the 1,3,4-oxadiazole ...

Myeloperoxidase (MPO) is involved in acute and chronic inflammatory diseases. The source of MPO in acute liver diseases is still a matter of debate. Therefore, we analysed MPO-gene expression on sections from normal and acutely damaged [carbon tetrachloride-(CCl(4)) or whole liver γ-Irradiation] rat liver by immunohistochemistry, real time PCR and ...

In a previous study, we obtained histologic documentation of liver gas embolism in the rat model of rapid decompression. The aim of the study was to assess in the same model occurrence and time course of liver embolism using 2-D ultrasound imaging, and to explore by this means putative liver ...

AIM: To explore protective effect of probucol on liver injury induced by carbon tetrachloride (CCl(4)) in rats. METHODS: We used CCl(4) to induce a rat model of liver injury. Some of those rats were treated with an oral administration of probucol. Liver function, blood lipid, liver tissue malondialdehyde (MDA), superoxide ...

We previously reported that machine perfusion (MP) performed at 20°C enhanced the preservation of steatotic rat livers. Here, we tested whether rat livers retrieved 30min after cardiac arrest (NHBDs) were better protected by MP at 20°C than with cold storage. We compared the recovery of livers from NHBDs with organs ...

We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer (14)C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy ...

Abstract Augmenter of Liver Regeneration (Alrp) enhances, through unknown mechanism/s, hepatocyte proliferation only when administered to partially hepatectomized (PH) rats. Liver resection, besides stimulating hepatocyte proliferation, induces reactive oxygen species (ROS), triggering apoptosis. To clarify the role of Alrp in the process of liver regeneration, hepatocyte proliferation, apoptosis, ROS-induced parameters ...

This study was designed to investigate the protective effects of caffeic acid phenethyl ester on carbon tetrachloride-induced liver damage in rats. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected with carbon tetrachloride every other day for 1 ...

Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher ...

Aim:  Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors, are well known to reduce low-density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti-inflammatory ...

Aflatoxin B₁ (AFB₁) is a DNA-binding toxin that contributes to the burden of liver cancer in tropical areas. AFB₁-DNA adducts are powerful biomarkers that discern individual and population risk from exposure to this carcinogen. The discovery of concordance between the metabolic pathways of the male Fischer rat and humans allowed ...

Molybdenum is an essential trace micronutrient element that plays an important role in animal and plant physiology. Molybdenum is a constituent of at least three mammalian metalloflavoproteins: xanthine oxidase, aldehyde oxidase and sulphite oxidase. In the present study, the hepatoprotective potential of sodium molybdate was investigated against carbon tetrachloride (CCl(4))-induced ...

Abstract Humans occasionally become infected with acanthocephalans, particularly Moniliformis moniliformis. Although several anthelmintics have been used, no controlled studies have been conducted to assess the efficacy of common anthelmintics in the treatment of moniliformiasis. The effectiveness of pyrantel pamoate, ivermectin, praziquantel, niclosamide, thiabendazole, and mebendazole was evaluated in the treatment ...

The hepatic pharmacokinetics of five selected cationic drugs (propranolol, labetalol, metoprolol, antipyrine and atenolol) was studied in the liver from control rats and from those with high-fat emulsion-induced non-alcoholic steatohepatitis (NASH). Studies were undertaken using an in situ perfused rat liver (IPRL) and multiple indicator dilution (MID), with outflow data ...

We present an improved cytotoxicity test for reactive metabolites, in which the S9 microsomal fraction of rat liver homogenate is encapsulated in alginate gel microbeads to avoid cytotoxic effects of S9-self-generated toxicants, microsomal lipid peroxides. The S9-encapsulated gel microbeads were prepared by a coaxial two-fluid nozzle and surfaces of the ...