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Int J Geriatr Psychiatry 2019 Jan 4. Epub 2019 Jan 4.

Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.

Objective: Pyrus pashia has traditionally been used as a therapeutic agent including sedative. In this regard, hydroethanolic extract of Pyrus pashia (HEPP) was screened for phytochemical investigation, acute toxicity, and sedative-hypnotic activity to provide a scientific rationale to its ethno-medicinal uses.

Methods: Mice were used in acute toxicity test; sedative potential was observed in open field test while thiopental-induced sleeping time and barbiturate-induced sleeping time tests were used for the assessment of hypnotic like effects of HEPP. Read More

Environ Mol Mutagen 2019 01 19;60(1):42-46. Epub 2018 Oct 19.

Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.

The Pig-a assay is an emerging and promising in vivo method to determine mutagenic potential of chemicals. Since its development in 2008, remarkable progress has been made in harmonizing and characterizing the test procedures, primarily using known mutagenic chemicals. The purpose of the present study was to evaluate specificity of the Pig-a assay using two nongenotoxic and well-characterized rodent liver carcinogens, phenobarbital and clofibrate, in male F344/DuCrl rats. Read More

Rocz Panstw Zakl Hig 2018 ;69(3):307-314

Department of Toxicology and Health Risk Assessment, National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland

Background: The changes in DNA methylation are considered as one of the early events in hepatocarcinogenesis.

Objective: We evaluated the ability of phenobarbital (PB) – the most widely used anticonvulsant worldwide and classical rodent liver carcinogen – to cause the promoter region of the c-myc protooncogene hypomethylation as well as changes of mRNA level of this gene. Moreover, the expression of Dnmt1 protein in rat treated with this compound was analyzed. Read More

Neurotox Res 2019 Jan 24;35(1):173-182. Epub 2018 Aug 24.

Department of Pharmacology and Physiology, Georgetown University, Washington, DC, 20007, USA.

The developing brain is uniquely susceptible to drug-induced increases in programmed cell death or apoptosis. Many compounds, including anticonvulsant drugs, anesthetic agents, and ethanol, when administered in a narrow postnatal window in rodents, result in increased pruning of neurons. Here, we report that dimethyl sulfoxide (DMSO) triggers widespread neurodegeneration in the immature (postnatal day, P7) rat brain, an effect consistent with a prior report in neonatal mice. Read More

Environ Sci Pollut Res Int 2018 Sep 27;25(25):25383-25389. Epub 2018 Jun 27.

Programa de Pós-Graduação em Ciências Ambientais, Laboratórios Integrados de Pesquisas em Ciências Químicas, Instituto de Ciências Naturais, Humanas e Sociais, Universidade Federal de Mato Grosso, Câmpus de Sinop, Av. Alexandre Ferronato, 1200, Setor Industrial, Sinop, MT, 78557-267, Brazil.

The toxicity of Roundup Original® (GLY), a glyphosate-based herbicide widely used in crops in Mato Grosso state, was determined in hybrid fish jundiara or pintado da Amazônia. The 96 h-LC of GLY was 13.57 mg L. Read More

J Hazard Mater 2018 Sep 17;358:494-502. Epub 2018 May 17.

Masaryk University, Faculty of Science, RECETOX, Kamenice 753/5, 625 00 Brno, Czech Republic. Electronic address:

Growth inhibition of freshwater microalga Pseudokirchneriella subcapitata caused by a waste water treatment plant (WWTP) effluent extract was investigated using an effect directed analysis (EDA) approach. The objective was to identify compounds responsible for the toxicity by combining state-of-the-art sampling, bioanalytical, fractionation and non-target screening techniques. Three fractionation steps of the whole extract were performed and bioactive fractions were analysed with GC (xGC)-MS and LC-HRMS. Read More

Ecotoxicol Environ Saf 2018 Sep 21;160:94-103. Epub 2018 May 21.

Center for Marine Environmental Studies, Ehime University, Bunkyo-cho 2-5, Matsuyama, Ehime prefecture, 790-8577 Japan. Electronic address:

This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. Read More

Food Chem Toxicol 2018 Mar 7;113:322-327. Epub 2018 Feb 7.

Environmental Toxicology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004, India. Electronic address:

Tartrazine is a synthetic lemon yellow azo dye primarily used as a food coloring. The present study aimed to screen the neurobiochemical effects of Tartrazine in Wistar rats after administering the Acceptable Daily Intake (ADI) level. Tartrazine (7. Read More

Neurotox Res 2018 08 7;34(2):173-187. Epub 2018 Feb 7.

Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6. Read More

Biol Pharm Bull 2018 ;41(2):247-253

Department of Pharmacognosy, School of Pharmacy, Kitasato University.

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. Read More

Biochemistry 2018 02 30;57(7):1262-1273. Epub 2018 Jan 30.

Department of Biochemistry and Molecular Biology, ‡Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205-7199, United States.

Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC value of 8 μM and exhibited 5-10-fold specificity for hpol η over replicative pols. We conclude from kinetic analyses, chemical footprinting assays, and molecular docking that PNR-7-02 binds to a site on the little finger domain and interferes with the proper orientation of template DNA to inhibit hpol η. Read More

Arch Toxicol 2018 Feb 21;92(2):953-966. Epub 2017 Dec 21.

Department of Medicine I, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.

Many frequently prescribed drugs are non-genotoxic carcinogens (NGC) in rodent liver. Their mode of action and health risks for humans remain to be elucidated. Here, we investigated the impact of two model NGC, the anti-epileptic drug phenobarbital (PB) and the contraceptive cyproterone acetate (CPA), on intrahepatic epithelial-mesenchymal crosstalk and on growth of first stages of hepatocarcinogenesis. Read More

Georgian Med News 2017 Nov(272):138-144

Azerbaijan Medical University, Baku, Azerbaijan.

Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poisoning in Azerbaijan. We collected and analyzed the data on all cases of acute poisoning by psychopharmacological drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. Read More

Eur J Med Chem 2018 Jan 27;143:829-842. Epub 2017 Nov 27.

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal; Department of Chemistry, University of Beira Interior, 6201-001 Covilhã, Portugal.

Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC values of 24. Read More

Pharmacogn Mag 2017 Oct 11;13(Suppl 3):S567-S572. Epub 2017 Oct 11.

Department of Biochemistry, S.D.M. Centre for Research in Ayurveda and Allied Sciences, Kuthpady, Udupi, Karnataka, India.

Background: Aluminum chloride (AlCl) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine.

Objective: To evaluate the neuroprotective activity of hydroalcoholic extract of in chronic AlCl-induced neurotoxicity in Swiss albino mice. Read More

J Toxicol Sci 2017 ;42(6):773-788

Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd.

High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations. Read More

Drug Metab Lett 2017;11(2):144-148

PK Sciences, Global Biotransformation, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, United States.

Background: 4-(piperazin-1-yl)-8-(trifluoromethyl)pyrido[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (1) is a small-molecule which demonstrated a sub-nM inhibitory potency toward the histamine H4 receptor (H4R). However, it was found to be mutagenic in an in vitro Ames assay. Metabolic bioactivation of 1 could potentially arise from the piperazine moiety by forming reactive intermediates such as glyoxal, aldehyde-imine and/or iminium ion, which could all lead to genotoxicity. Read More

Mol Med Rep 2017 Aug 8;16(2):1559-1564. Epub 2017 Jun 8.

Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, P.R. China.

Diosgenin is a steroidal saponin extract from numerous plants, including Solanum and Dioscorea species, and has been reported to possess neuroprotective activity. However, the role of diosgenin in neuropathic pain remains unclear. The present study examined the effects of diosgenin on allodynia and the levels of inflammatory mediators in rats following neuropathic pain evoked by chronic constriction injury (CCI). Read More

Int J Mol Sci 2017 Sep 21;18(10). Epub 2017 Sep 21.

Departamento de Investigación Agroambiental, IMIDRA, Finca "El Encín", Autovía del Noreste A-2 Km 38.2, 28800 Alcalá de Henares, Madrid, Spain.

Plant growth promoting endophytic bacteria (PGPB) isolated from were inoculated in two cultivars of (VR and D19) growing on sand supplemented with 0.1 mM Cd or 1 mM Zn. Plant growth, concentrations of metals and thiobarbituric acid (TBA) reactive compounds were determined. Read More

J Pharmacol Exp Ther 2017 12 19;363(3):336-347. Epub 2017 Sep 19.

GlaxoSmithKline, King of Prussia, Pennsylvania (JLA, DFA, DF, TS, KJD, MP, MB, KW) and while at GlaxoSmithKline, King of Prussia, Pennsylvania (LL, EHDF, CE-M).

Decreased erythropoietin (EPO) production, shortened erythrocyte survival, and other factors reducing the response to EPO contribute to anemia in patients who have a variety of underlying pathologies such as chronic kidney disease. Treatment with recombinant human EPO (rHuEPO) at supraphysiologic concentrations has proven to be efficacious. However, it does not ameliorate the condition in all patients, and it presents its own risks, including cardiovascular complications. Read More

Anesthesiology 2017 11;127(5):838-851

From the Department of Physiology and Pharmacology (M.-C.K.) and the Department of Physiology and Pharmacology and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.

Background: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

Methods: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Read More

Clin Toxicol (Phila) 2018 Feb 1;56(2):81-89. Epub 2017 Sep 1.

e McGill University Health Centre , Emergency Medicine, McGill University , Montreal , QC , Canada.

Context: Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate that lamotrigine overdose is usually benign. However, there are reported cases of cardiac arrest and mortality following lamotrigine overdose. Read More

Oxid Med Cell Longev 2017 26;2017:2186383. Epub 2017 Jul 26.

Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, China.

Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. Read More

J Toxicol Sci 2017 ;42(4):491-497

Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Health and Nutrition.

Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. Read More

Neurotox Res 2017 Oct 22;32(3):460-472. Epub 2017 Jun 22.

Department of Neonatology, Charité University Medical Center, Augustenburger Platz 1, 13353, Berlin, Germany.

Phenobarbital is the most commonly used drug for the treatment of neonatal seizures but may induce neurodegeneration in the developing brain. Methylxanthine caffeine is used for the treatment of apnea in newborn infants and appears to be neuroprotective, as shown by antiapoptotic and anti-inflammatory effects in oxidative stress models in newborn rodents and reduced rates of cerebral palsy in human infants treated with caffeine. We hypothesized that caffeine may counteract the proapoptotic effects of phenobarbital in newborn rats. Read More

Pediatr Emerg Care 2018 Mar;34(3):e51-e54

Vilazodone hydrochloride is the first member in a new class of antidepressants called indolealkylamines and was approved for use in the United States in 2011 for major depressive disorder. It has a combined mechanism of action of a selective serotonin reuptake inhibitor and a partial agonist of serotonin 5-HT1A receptors. It has not been approved for use in the pediatric population, and toxicity from exploratory vilazodone ingestion has been rarely described to date. Read More

Toxicol Pathol 2017 06 5;45(4):493-505. Epub 2017 Jun 5.

3 Food Safety Commission, Cabinet Office, Minato-ku, Tokyo, Japan.

We previously reported the contribution of constitutive androstane receptor (CAR) in cytotoxicity-related hepatocarcinogenesis induced by oxadiazon (OX) or acifluorfen (ACI), two pesticides categorized as protoporphyrinogen oxidase (PROTOX) inhibitors. The molecular characteristics of preneoplastic and neoplastic lesions induced by OX and ACI were immunohistochemically compared to those by phenobarbital (PB), a typical CAR activator, in wild-type (WT) and CAR knockout (CARKO) mice after diethylnitrosamine initiation. We focused on changes in β-catenin and its transcriptional product glutamine synthetase (GS). Read More

Pediatrics 2017 May;139(5)

Divisions of Medicine Critical Care,

A 15-year-old female subject presented comatose, in respiratory failure and shock, after the intentional ingestion of ∼280 extended-release 200-mg carbamazepine tablets with a peak serum concentration of 138 µg/mL (583.74 µmol/L). The patient developed clinical seizures and an EEG pattern of stimulus-induced rhythmic, periodic, or ictal discharges, suggestive of significant cortical dysfunction. Read More

Toxicol Sci 2017 08;158(2):367-378

Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, CH-4057 Basel, Switzerland.

Derisking xenobiotic-induced nongenotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster noncoding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB). Read More

Food Chem Toxicol 2017 Nov 8;109(Pt 1):690-702. Epub 2017 May 8.

Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address:

Identification of sensitive and novel biomarkers or endpoints associated with toxicity and carcinogenesis is of a high priority. There is increasing interest in the incorporation of epigenetic and metabolic biomarkers to complement apical data; however, a number of questions, including the tissue specificity, dose-response patterns, early detection of those endpoints, and the added value need to be addressed. In this study, we investigated the dose-response relationship between apical, epigenetic, and metabolomics endpoints following short-term exposure to experimental hepatotoxicants, clofibrate (CF) and phenobarbital (PB). Read More

Georgian Med News 2017 Mar(264):127-1311

Tbilisi State Medical University I.Kutateladze Institute of Pharmacochemistry; Iv. Javakhishvili Tbilisi State University, Georgia.

Antiseizure activity of Cephalaria gigantea root extract was studied using PTZ- and/or audiogenic seizure models in outbred Wistar and inbred Krouchinsky- Molodkina rats respectively. In PTZ - model onset of tonic- clonic seizures, latencies to the beginning of the seizure activity, and mortality, and similarly in audiogenic seizures behavioral convulsive reactions , facial automatisms and latency to wild running were evaluated. The extract is used traditionally in Georgian folk medicine as anticonvulsant drug. Read More

Leg Med (Tokyo) 2017 Mar 16;25:52-58. Epub 2017 Jan 16.

Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan.

Cerebrospinal fluid (CSF) is routinely subjected to gross evaluation in postmortem investigations; however, its use in chemical evaluations has not been fully realized. Analysis of nuclear magnetic resonance (NMR) spectra with pattern recognition methods was applied to CSF samples. Rats were treated with pentylenetetrazol (PTZ) to induce seizure or pentobarbital (PB) to induce coma, and postmortem CSF was collected after CO gas euthanization. Read More

Chem Biol Interact 2017 May 14;270:41-50. Epub 2017 Apr 14.

Department of Pharmacology, Faculty of Medicine, Beni-Suef University, Egypt.

The objective of the current study was to investigate the possible chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using DEN for initiation and PB as a promoting agent. Read More

Sud Med Ekspert 2017;60(2):36-40

Saint-Petersburg State Chemical and Pharmaceutical Academy, Saint-Petersburg, Russia, 197376.

The objective of the present study was to develop and validate the method for the extraction of toxic substances from the hair samples as exemplified by enzymatic hydrolysis of barbituric acid derivatives. The experiments were carried out with the use of laboratory animals (white female rats and albino guinea pigs) that had been daily given a phenobarbital solution per os during 4 months preceding the study. The hairs obtained from the experimental animals were subjected to acid hydrolysis with a 6 mole hydrochloric acid and enzymatic hydrolysis with the use of chymopsin, trypsin, chymotrypsin, and papain solutions. Read More

Pharm Biol 2017 Dec;55(1):1513-1520

a Department of Pathology, Faculty of Veterinary Medicine , Cairo University , Giza , Egypt.

Context: Camel milk (CM) is recommended for liver disease patients in Egypt for a strong belief that it has a curative effect.

Objective: The effect of consumption of CM with or without chemotherapeutic drug cisplatin was evaluated on induced hepatocarcinogenesis in rats.

Materials And Methods: Wistar male rats (56) were divided into eight groups (7 rats each). Read More

Food Chem Toxicol 2017 Jul 22;105:1-7. Epub 2017 Mar 22.

Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193 Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain. Electronic address:

Lipid peroxidation products can induce tissue damage and are implicated in diverse pathological conditions, including aging, atherosclerosis, brain disorders, cancer, lung and various liver disorders. Since in vivo studies produce relevant information, we have selected Drosophila melanogaster as a suitable in vivo model to characterise the potential risks associated to two lipid peroxidation products namely 4-oxo-2-nonenal (4-ONE) and 4-hydroxy-hexenal (4-HHE). Toxicity, intracellular reactive oxygen species production, and genotoxicity were the end-points evaluated. Read More

Clin Biochem 2017 Sep 11;50(13-14):784-790. Epub 2017 Mar 11.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 1301 Medical Center Drive, 4918B TVC, Nashville, TN 37232, USA. Electronic address:

Objectives: Drug screening in neonates is traditionally performed using meconium, but cord tissue has been proposed as an alternative specimen. This study compares the detection of drugs in a large number of paired meconium and umbilical cord tissue samples from subjects at risk of in utero drug exposure.

Design And Methods: Physician-ordered toxicology results and clinical information were collected in a retrospective review of subject medical records. Read More

Toxicol Pathol 2016 12;44(8):1146-1159

1 Department of Pathology, Botucatu Medical School, UNESP-São Paulo State University, Botucatu, São Paulo, Brazil.

The medium-term multiorgan initiation-promotion chemical bioassay (diethylnitrosamine, methyl-nitrosourea, butyl-hydroxybutylnitrosamine, dihydroxypropylnitrosamine, dimethylhydrazine [DMBDD]) with the Fischer 344 rat was proposed as an alternative to the conventional 2-year carcinogenesis bioassay for regulatory purposes. The acronym DMBDD stands for the names of five genotoxic agents used for initiation of multiorgan carcinogenesis. The Brazilian Agency for the Environment officially recognized a variation of this assay (DMBDD) as a valid method to assess the carcinogenic potential of agrochemicals. Read More

Physiol Behav 2017 05 6;173:132-143. Epub 2017 Feb 6.

Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Neuropharmacology Group, ASAM, Macquarie University, Sydney, NSW, Australia.

Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice. CMS and MPTP/p-coexposed C57BL/6 mice exhibited low neuromuscular strength and stride length with enhanced oxidative stress and inflammation as compared to CMS or MPTP/p alone exposed mice. Read More

Pharmacology 2017 21;99(5-6):205-215. Epub 2017 Jan 21.

College of Pharmacy, Chongqing Medical University, Chongqing, China.

Aim: To examine the effect of synthetic muscone on the expression of CYP1A2 and CYP3A4 enzymes in human liver L02 cells and in the liver tissue of Kunming mice.

Methods: The L02 hepatic cell line was used to study the effect of low (10-4 μmol/L), middle (10-3 μmol/L), and high concentrations (10-2 μmol/L) of muscone on the expression of CYP1A2 and CYP3A4 enzymes. In addition, the cytochrome P450 (CYP) expression was investigated in Kunming mice after the administration of 10 mg/kg (low), 50 mg/kg (middle), and 100 mg/kg (high) dose of muscone for 6 days. Read More

Pain 2017 05;158(5):856-867

aRudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Leipzig, Germany bCarl-Ludwig-Institut für Physiologie, Universität Leipzig, Leipzig, Germany.

The melastatin-related transient receptor potential (TRP) channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Because TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Read More

Drug Metab Dispos 2017 03 6;45(3):330-335. Epub 2017 Jan 6.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut

Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. Read More

Arch Toxicol 2017 Aug 6;91(8):2895-2907. Epub 2017 Jan 6.

Department of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074, Tübingen, Germany.

The agricultural fungicides cyproconazole and prochloraz exhibit hepatotoxicity in rodent studies and are tumorigenic following chronic exposure. Both substances are suspected to act via a CAR (constitutive androstane receptor)/PXR (pregnane-X-receptor)-dependent mechanism. Human relevance of these findings is under debate. Read More

Addiction 2017 03 20;112(3):486-493. Epub 2016 Nov 20.

Department of Forensic Medicine, Monash University, Southbank, VIC, Australia.

Background And Aims: There are numerous factors putting health-care professionals (HCP) at a higher risk of substance abuse and premature death, including high-stress jobs, access to controlled substances, long hours of practice and constant contact with the critically ill. This study aimed to examine fatal drug toxicity in this high-risk cohort, in order to: (1) estimate the rate of drug-caused deaths of Australian HCPs; (2) describe the key characteristics of the cohort; and (3) examine the relationship between HCP occupation and drug type, or intent.

Design: Retrospective cohort study. Read More

Sci Rep 2016 11 17;6:37426. Epub 2016 Nov 17.

Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 M.G. Marg, Post Box No. 80, Lucknow-226 001, Uttar Pradesh, India.

Epigenetic studies were carried in the rat offsprings, born to dams treated with cypermethrin (orally; 5.0 mg/kg) from gestation day (GD) 5 to 21 and rechallenged with cypermethrin (orally; 10 mg/kg for 6 days), at adulthood (12 weeks) to understand the mechanism underlying the overexpression of cerebral cytochrome P450s (CYPs) in exposed offsprings. The data revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of CYP1A- and 2B- isoenzymes in the brain isolated from rechallenged animals. Read More

Vet Q 2016 Dec 10;36(4):242-246. Epub 2016 May 10.

a Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine , Ghent University , Merelbeke , Belgium.

Psychopharmacology (Berl) 2017 01 25;234(2):281-291. Epub 2016 Oct 25.

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.

Background: Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation.

Objectives: This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures.

Results: CYT administered intraperitoneally (i. Read More