6,409 results match your criteria Toxicity Sedative-Hypnotics


Investigating tissue bioconcentration and the behavioural effects of two pharmaceutical pollutants on sea trout (Salmo trutta) in the laboratory and field.

Aquat Toxicol 2019 Feb 1;207:170-178. Epub 2018 Dec 1.

Department of Ecology and Environmental Science, Umeå University, SE-90187, Umeå, Sweden; Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, SE-90183, Umeå, Sweden.

Pharmaceuticals entering aquatic ecosystems via wastewater effluents are of increasing concern for wild animals. Because some pharmaceuticals are designed to modulate human behaviour, measuring the impacts of exposure to pharmaceuticals on fish behaviour has become a valuable endpoint. While laboratory studies have shown that pharmaceuticals can affect fish behaviour, there is a lack of understanding if behaviour is similarly affected in natural environments. Read More

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http://dx.doi.org/10.1016/j.aquatox.2018.11.028DOI Listing
February 2019
1 Read

The anti-apoptotic effect of nerve growth factor on propofol-induced neurotoxicity in hippocampal neurons is Rac1 dependent.

Pharmazie 2018 12;73(12):706-710

Propofol has been considered as a near-ideal anesthetic agent since its introduction 40 years ago. However, the side effects of propofol including bacterial contamination, hyperlipidemia, and neurotoxicity also aroused attention. Nerve growth factor (NGF) plays a pivotal role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Read More

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http://dx.doi.org/10.1691/ph.2018.8726DOI Listing
December 2018
2 Reads

Determination of emerging chlorinated byproducts of diazepam in drinking water.

Chemosphere 2019 Mar 15;218:223-231. Epub 2018 Nov 15.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, 100013, China. Electronic address:

Diazepam (DZP) is often found in source water and drinking water at dozens of nanograms per liter levels. The transformation of DZP in water chlorination disinfection process has aroused new concern because the toxic disinfection byproducts (DBPs) might be produced. However, the DBPs of DZP have not been fully identified, and their occurrence levels in drinking water have not been reported. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2018.11.076DOI Listing
March 2019
1 Read

Pilot studies evaluating the nongenotoxic rodent carcinogens phenobarbital and clofibrate in the rat Pig-a assay.

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

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http://dx.doi.org/10.1002/em.22232DOI Listing
January 2019
2 Reads

Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A.

Biochim Biophys Acta Mol Basis Dis 2018 11 18;1864(11):3618-3628. Epub 2018 Aug 18.

INSERM UMR1149/Inflammation Research Center (CRI), Team "From inflammation to cancer in digestive diseases" labeled by "la Ligue Nationale contre le Cancer", Paris-Diderot University, DHU UNITY, 75018 Paris, France. Electronic address:

Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09254439183031
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http://dx.doi.org/10.1016/j.bbadis.2018.08.023DOI Listing
November 2018
15 Reads

Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar.

J Fish Biol 2018 Dec 28;93(6):1069-1081. Epub 2018 Nov 28.

Marine Laboratory, Marine Scotland Science, Aberdeen, UK.

Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research lags behind methodologies in place for mammalian studies. With a need for individual monitoring and non-lethal sampling, the effect of repeat anaesthesia on experimental fish needs to be better understood. This study analyses the effect of repeat anaesthesia with MS-222, metomidate and AQUI-S upon the gill and general health of post-smolt Atlantic salmon Salmo salar. Read More

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http://dx.doi.org/10.1111/jfb.13803DOI Listing
December 2018
3 Reads
1.658 Impact Factor

Midazolam is effective to reduce cortical network activity in organotypic cultures during severe cholinergic overstimulation with soman.

Toxicol Lett 2018 Nov 27;297:19-23. Epub 2018 Aug 27.

Experimental Anesthesiology Section, Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Electronic address:

Intoxication with organophosphorus compounds can result in life-threatening organ dysfunction and refractory seizures. Sedation or hypnosis is essential to facilitate mechanical ventilation and control seizure activity. The range of indications for midazolam includes both hypnosis and seizure control. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.08.016DOI Listing
November 2018
25 Reads
3.262 Impact Factor

Effect of aflatoxin B, benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells.

Food Chem Toxicol 2018 Nov 26;121:214-223. Epub 2018 Aug 26.

Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Rd, Jefferson, AR, 72079, USA. Electronic address:

The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk highlights the need for developing reliable time- and cost-effective approaches for carcinogen detection and identification. To address this issue, we investigated the utility of high-throughput microarray gene expression and next-generation genome-wide DNA methylation sequencing for the in vitro identification of genotoxic and non-genotoxic carcinogens. Terminally differentiated and metabolically competent human liver HepaRG cells were treated at minimally cytotoxic concentrations of (i) the genotoxic human liver carcinogen aflatoxin B (AFB1) and its structural non-carcinogenic analog aflatoxin B (AFB2); (ii) the genotoxic human lung carcinogen benzo[a]pyrene (B[a]P) and its non-carcinogenic isomer benzo[e]pyrene (B[e]P); and (iii) the non-genotoxic liver carcinogen methapyrilene for 72 h and transcriptomic and DNA methylation profiles were examined. Read More

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http://dx.doi.org/10.1016/j.fct.2018.08.034DOI Listing
November 2018
12 Reads

Catatonia After Liver Transplantation.

Ann Transplant 2018 Aug 28;23:608-614. Epub 2018 Aug 28.

Department of Surgery, Division of Abdominal Transplant, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

BACKGROUND Central nervous system complications after transplantation occur in up to 40% of recipients and these complications are associated with increased length of hospital stay and mortality. Catatonia is a neuropsychiatric clinical syndrome which has been described in case reports and in a small case series as occurring in the immediate post-solid organ transplantation (SOT) period, and it has been attributed to calcineurin inhibitor neurotoxicity, psychological vulnerability, and depression. Among transplant recipients, the incidence of catatonia is unknown; it may be under diagnosed in part due to a broad differential diagnosis in the post-transplantation setting, which includes hypoactive delirium, non-convulsive status epilepticus, drug toxicity, conversion disorder, and volitional uncooperativeness. Read More

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https://www.annalsoftransplantation.com/abstract/index/idArt
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http://dx.doi.org/10.12659/AOT.910298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248284PMC
August 2018
8 Reads

Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver

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

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November 2018
1 Read

Optimal concentration of the transversus abdominis plane block in enhanced recovery after surgery protocols for patients of advanced age undergoing laparoscopic rectal cancer surgery.

J Int Med Res 2018 Nov 15;46(11):4437-4446. Epub 2018 Aug 15.

1 Anesthesiology Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Objective: The transversus abdominis plane (TAP) block ameliorates visual analogue scale scores and decreases morphine requirements, but its role remains unclear. Patients of advanced age are susceptible to local anesthetic intoxication. We aimed to identify an optimal concentration that can be used in enhanced recovery after surgery (ERAS) without compromising analgesic efficacy. Read More

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http://dx.doi.org/10.1177/0300060518790699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259369PMC
November 2018
9 Reads

Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by targeting NLRP3 via miR-381.

J Biochem Mol Toxicol 2018 Nov 13;32(11):e22211. Epub 2018 Aug 13.

Department of Pain, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250012, Shandong, China.

Dexmedetomidine (Dex) is an agonist of α2-adrenergic receptors, and it is used as an anxiety reducing, sedative, and pain medication in clinical. Studies have shown that dexmedetomidine protects against lipopolysaccharide (LPS)-induced acute lung injury; however, the underlying mechanism is still unclear. To investigate, an acute lung injury mouse model was induced by intraperitoneal injection of LPS. Read More

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http://doi.wiley.com/10.1002/jbt.22211
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http://dx.doi.org/10.1002/jbt.22211DOI Listing
November 2018
9 Reads

Serotonin Syndrome in the Perioperative Setting.

Am J Case Rep 2018 Jul 16;19:833-835. Epub 2018 Jul 16.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Read More

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http://dx.doi.org/10.12659/AJCR.909497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061453PMC
July 2018
14 Reads

In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of and In Silico of Certain Compounds Present in This Species.

Biomed Res Int 2018 13;2018:3868070. Epub 2018 May 13.

Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, CA 92182, USA.

Background: (flatweed) from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. Read More

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http://dx.doi.org/10.1155/2018/3868070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016213PMC
January 2019
7 Reads

Dexmedetomidine protects high-glucose induced apoptosis in human retinal pigment epithelial cells through inhibition on p75(NTR).

Biomed Pharmacother 2018 Oct 11;106:466-471. Epub 2018 Jul 11.

Department of Anesthesiology, Jining First People's Hospital, Jining, 272100, China. Electronic address:

Background: In both human patients and animals, diabetic condition of high blood glucose induced significant apoptotic responses in retinal pigment epithelial (RPE) cells. In this work, we used an in vitro culture model of human ARPE-19 cells to evaluate whether dexmedetomidine (DEX) may protect high d-glucose (DG)-induced diabetic apoptosis.

Methods: ARPE-19 cells were incubated with DG in vitro to induce apoptosis. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.06.117DOI Listing
October 2018
5 Reads

A Case Study Involving U-47700, Diclazepam and Flubromazepam-Application of Retrospective Analysis of HRMS Data.

J Anal Toxicol 2018 Nov;42(9):655-660

Forensic Science SA (Toxicology), Adelaide, South Australia, Australia.

The number of new psychoactive substances (NPS) available is constantly increasing, making it difficult for toxicology laboratories to keep screening methods up to date. Full scan high-resolution mass spectrometry (HRMS) is a versatile technique which allows for progressive updating of spectral databases to increase the scope of screening. It also allows for retrospective screening of data-specifically, reprocessing of data files using an updated spectral database without the need for re-extraction or reanalysis. Read More

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http://dx.doi.org/10.1093/jat/bky039DOI Listing
November 2018
11 Reads

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

Yakugaku Zasshi 2018 ;138(6):809-813

Graduate School of Pharmaceutical Sciences, The University of Tokyo.

 During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. Read More

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https://www.jstage.jst.go.jp/article/yakushi/138/6/138_17-00
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http://dx.doi.org/10.1248/yakushi.17-00213-1DOI Listing
August 2018
26 Reads

Propofol Protects Rat Cardiomyocytes from Anthracycline-Induced Apoptosis by Regulating MicroRNA-181a and .

Oxid Med Cell Longev 2018 18;2018:2109216. Epub 2018 Apr 18.

Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.

We aimed to evaluate the cardioprotective effect and mechanism of propofol in anthracycline-induced cardiomyocyte apoptosis. We selected the rat myocardial cell line, H9c2, and primary cardiomyocytes for study. The cardiomyocytes were treated with vehicle, Adriamycin® (ADM), propofol, or a combination of ADM and propofol. Read More

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http://dx.doi.org/10.1155/2018/2109216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932430PMC
October 2018
9 Reads

Influence of ethanol on the metabolism of alprazolam.

Expert Opin Drug Metab Toxicol 2018 Jun;14(6):551-559

a Department of Forensic Medicine, School of Basic Medical Sciences , Fudan University , Shanghai , China.

Background: Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown.

Research Design And Methods: The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. Read More

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http://dx.doi.org/10.1080/17425255.2018.1483338DOI Listing
June 2018
3 Reads

Benzodiazepine-refractory status epilepticus, neuroinflammation, and interneuron neurodegeneration after acute organophosphate intoxication.

Biochim Biophys Acta Mol Basis Dis 2018 09 23;1864(9 Pt B):2845-2858. Epub 2018 May 23.

Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, College of Medicine, Bryan, TX 77807, USA. Electronic address:

Nerve agents and some pesticides such as diisopropylfluorophosphate (DFP) cause neurotoxic manifestations that include seizures and status epilepticus (SE), which are potentially lethal and carry long-term neurological morbidity. Current antidotes for organophosphate (OP) intoxication include atropine, 2-PAM and diazepam (a benzodiazepine for treating seizures and SE). There is some evidence for partial or complete loss of diazepam anticonvulsant efficacy when given 30 min or later after exposure to an OP; this condition is known as refractory SE. Read More

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http://dx.doi.org/10.1016/j.bbadis.2018.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066461PMC
September 2018
5 Reads

Effects on the hepatic transcriptome of chicken embryos in ovo exposed to phenobarbital.

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

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http://dx.doi.org/10.1016/j.ecoenv.2018.05.033DOI Listing
September 2018
3 Reads

Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats.

Neurol Res 2018 Sep 23;40(9):767-773. Epub 2018 May 23.

a Department of Anesthesiology , The First Affiliated Hospital of Guangxi Medical University , Nanning , China.

Objective:  Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning (HPC) was previously demonstrated to provide neuroprotection and brain recovery from either acute or chronic neurodegeneration in several cellular and animal models. Therefore, the present study was designed to investigate the protective effects of hypoxic preconditioning on apoptosis caused by propofol in neonatal rats. Read More

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http://dx.doi.org/10.1080/01616412.2018.1477545DOI Listing
September 2018
11 Reads

Beneficial Outcome of Urethane Treatment Following Status Epilepticus in a Rat Organophosphorus Toxicity Model.

eNeuro 2018 Mar-Apr;5(2). Epub 2018 Apr 17.

Department of Pharmacology, Emory University, Atlanta, GA 30322.

The efficacy of benzodiazepines to terminate electrographic status epilepticus (SE) declines the longer a patient is in SE. Therefore, alternative methods for ensuring complete block of SE and refractory SE are necessary. We compared the ability of diazepam and a subanesthetic dose of urethane to terminate prolonged SE and mitigate subsequent pathologies. Read More

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http://eneuro.org/lookup/doi/10.1523/ENEURO.0070-18.2018
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http://dx.doi.org/10.1523/ENEURO.0070-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952304PMC
January 2019
6 Reads

Differential sensitivity to the antifouling chemical medetomidine between wood frog and American toad tadpoles with evidence for low-dose stimulation and high-dose inhibition of metamorphosis.

Environ Sci Pollut Res Int 2018 Jul 5;25(20):19470-19479. Epub 2018 May 5.

Department of Biology, Gettysburg College, Gettysburg, PA, 17325, USA.

Antifouling chemicals are legacy contaminants in aquatic ecosystems. Previous experiments have shown that a 14-day exposure to the antifouling chemical medetomidine delays metamorphosis and reduces body mass in wood frog tadpoles. In the present study, we exposed wood frog tadpoles to medetomidine for 3, 7, and 10 days at 100 nM, 1 μM, and 10 μM. Read More

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http://dx.doi.org/10.1007/s11356-018-2168-yDOI Listing
July 2018
2 Reads

Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits.

Ann Ital Chir 2018 ;89:92-94

Ackground: Experimental surgery needs a pharmacological approach that can interfere with cardiac function.

Case Report: In a animal model of regenerative medicine of myocardium we use an anaesthesiological protocol that included Propofol, a benzodiazepine (Midazolam) and an alpha-2 adrenergic agent.

Results: In a group of 15 rabbits undergoing cardiac surgery we reported 1 arrhythmic complication during stem cell injection. Read More

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November 2018
12 Reads

Cytochrome P450-dependent drug oxidation activities in commercially available hepatocytes derived from human induced pluripotent stem cells cultured for 3 weeks.

J Toxicol Sci 2018 ;43(4):241-245

Hepatocyte-like cells differentiated from human induced pluripotent stem (iPS) cells are of great interest for applications in pharmacological research. For drug metabolism testing, commercially available hepatocytes derived from human iPS cells are generally recommended to be used 1 week after seeding on plates. In this study, however, after 3-4 weeks of culture according to the manufacturer's instructions, human cytochrome P450 (P450) 2C9- and 2C19-dependent diclofenac 4'-hydroxylation and omeprazole 5-hydroxylation activities of the iPS-derived hepatocytes had significantly increased above the activities at 1 week and had reached levels similar to those in HepaRG cells, a human hepatocyte-like cell line. Read More

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http://dx.doi.org/10.2131/jts.43.241DOI Listing
August 2018
4 Reads

The antihistamine diphenhydramine is demethylated by anaerobic wastewater microorganisms.

Chemosphere 2018 Jul 15;202:460-466. Epub 2018 Mar 15.

Department of Environmental Sciences, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA. Electronic address:

While emerging pharmaceutical contaminants are monitored in wastewater treatment and the environment, there is little information concerning their microbial metabolites. The transformation of diphenhydramine by microorganisms in anaerobic digester sludge was investigated using anaerobic cultures amended with 1 mM diphenhydramine as the sole carbon source. Complete transformation of the parent compound to a persistent metabolite occurred within 191 days. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2018.03.093DOI Listing
July 2018
4 Reads
3.340 Impact Factor

Effects of isopentyl ferulate on oxidative stress biomarkers and a possible GABAergic anxiolytic-like trait in Swiss mice.

Chem Biol Interact 2018 Jun 20;289:119-128. Epub 2018 Mar 20.

Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil; Laboratory of Research in Experimental Neurochemistry of Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil.

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.03.009DOI Listing
June 2018
4 Reads

Non-sedation of the neonate for radiologic procedures.

Authors:
Richard B Parad

Pediatr Radiol 2018 04 17;48(4):524-530. Epub 2018 Mar 17.

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, 75 Francis St., Rm. CWN418, Boston, MA, 02115, USA.

On Dec. 16, 2016, the U.S. Read More

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http://dx.doi.org/10.1007/s00247-017-4002-yDOI Listing
April 2018
2 Reads

Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases.

Chem Biol Interact 2018 Mar 19;284:48-55. Epub 2018 Feb 19.

Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Amentoflavone (AMF), an abundant natural biflavonoid found in many medicinal plants, displays various beneficial effects including anti-inflammatory, anti-oxidative and anti-cancer. Despite the extensive studies on pharmacological activities, the toxicity or undesirable effects of AMF are rarely reported. In this study, the inhibitory effects of AMF on human UDP-glucuronosyltransferases (UGTs) were carefully investigated. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.02.009DOI Listing
March 2018
22 Reads

Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats.

Physiol Behav 2018 05 16;188:298-310. Epub 2018 Feb 16.

Pharmacology Department, Federal University of Paraná, Paraná, Brazil. Electronic address:

Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms impairment and depression, important non-motor symptoms. It is known that toxin-based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6-OHDA) intranigral model, we first investigated the possible disturbances on circadian rhythms of locomotor activity. Read More

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http://dx.doi.org/10.1016/j.physbeh.2018.02.033DOI Listing
May 2018
5 Reads

Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner.

PLoS One 2018 15;13(2):e0192796. Epub 2018 Feb 15.

Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata, Japan.

The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia and sedation in critical patient care. However, the rare but severe complication propofol infusion syndrome (PRIS) can occur, especially in patients receiving high doses of propofol for prolonged periods. In vivo and in vitro evidence suggests that the propofol toxicity is related to the impaired mitochondrial function. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192796PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813975PMC
April 2018
4 Reads

Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain.

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

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http://dx.doi.org/10.1007/s12640-018-9872-8DOI Listing
August 2018
3 Reads

Dexmedetomidine stops benzodiazepine-refractory nerve agent-induced status epilepticus.

Epilepsy Res 2018 03 31;141:1-12. Epub 2018 Jan 31.

USAMRICD, Medical Toxicology Research Division, Neuroscience Branch, 2900 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010, United States.

Nerve agents are highly toxic chemicals that pose an imminent threat to soldiers and civilians alike. Nerve agent exposure leads to an increase in acetylcholine within the central nervous system, resulting in development of protracted seizures known as status epilepticus (SE). Currently, benzodiazepines are the standard of care for nerve agent-induced SE, but their efficacy quickly wanes as the time to treatment increases. Read More

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http://dx.doi.org/10.1016/j.eplepsyres.2018.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242267PMC
March 2018
5 Reads

Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.

Br J Anaesth 2018 Jan 23;120(1):188-196. Epub 2017 Nov 23.

School of Psychological Sciences, Sharet Building, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00070912175394
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http://dx.doi.org/10.1016/j.bja.2017.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246773PMC
January 2018
2 Reads

Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model.

Eur J Drug Metab Pharmacokinet 2018 Aug;43(4):423-430

Pacific University School of Pharmacy, 222 SE 8th Ave., Hillsboro, OR, 97123, USA.

Background And Objectives: While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluated the risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal. This study was undertaken to evaluate the potential toxicity of PG in patients with acute alcohol withdrawal treated with intermittent intravenous bolus doses of diazepam and/or lorazepam.

Methods: This is a retrospective case study using data collected from 18 randomly selected patients receiving one or both of these medications per a modified Clinical Institute Withdrawal Assessment for Alcohol (CIWA) Class 3 protocol. Read More

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http://dx.doi.org/10.1007/s13318-018-0462-1DOI Listing
August 2018
9 Reads

Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias.

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

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http://dx.doi.org/10.1248/bpb.b17-00803DOI Listing
August 2018
14 Reads

Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

PLoS One 2018 19;13(1):e0191070. Epub 2018 Jan 19.

Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.

Background: Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex) has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS)-induced neuroinflammation and sickness behavior in mice. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191070PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774758PMC
February 2018
5 Reads

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish.

Environ Toxicol Chem 2018 04 5;37(4):1175-1181. Epub 2018 Feb 5.

Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas, USA.

The zebrafish fish embryo toxicity (FET) test is increasingly employed for alternative toxicity studies, yet our previous research identified increased sensitivity of zebrafish slightly older than embryos employed in FET methods (0-4 d postfertilization [dpf]). We identified rapid steady-state accumulation of diphenhydramine across zebrafish embryo and larval stages. However, significantly (p < 0. Read More

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http://dx.doi.org/10.1002/etc.4068DOI Listing
April 2018
3 Reads

Mesenchyme-derived factors enhance preneoplastic growth by non-genotoxic carcinogens in rat liver.

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

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http://dx.doi.org/10.1007/s00204-017-2080-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818586PMC
February 2018
13 Reads

Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet.

Epilepsia 2018 01 24;59(1):79-91. Epub 2017 Nov 24.

Department of Neuroscience, IRCCS-Mario Negri Institute for Pharmacological Research, Milano, Italy.

Objective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Read More

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http://dx.doi.org/10.1111/epi.13950DOI Listing
January 2018
19 Reads

Protective effects of agomelatine on testicular damage caused by bortezomib.

Biotech Histochem 2017 21;92(8):552-559. Epub 2017 Nov 21.

b Biochemistry, Faculty of Veterinary Medicine , Ataturk University , Erzurum , Turkey.

Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. Read More

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http://dx.doi.org/10.1080/10520295.2017.1350748DOI Listing
February 2019
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Evaluation of the human relevance of the constitutive androstane receptor-mediated mode of action for rat hepatocellular tumor formation by the synthetic pyrethroid momfluorothrin.

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

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http://dx.doi.org/10.2131/jts.42.773DOI Listing
March 2018
25 Reads

Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells.

Neural Plast 2017 8;2017:9182748. Epub 2017 Oct 8.

Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. Read More

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http://dx.doi.org/10.1155/2017/9182748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651106PMC
July 2018
2 Reads

Genotoxicity of 4-(piperazin-1-yl)-8-(trifluoromethyl)pyrido[2,3-e][1,2,4] triazolo[4,3-a]pyrazine, a Potent H4 Receptor Antagonist for the Treatment of Allergy: Evidence of Glyoxal Intermediate Involvement.

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

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http://dx.doi.org/10.2174/1872312811666171106151730DOI Listing
October 2018
10 Reads

Evaluation of diphenhydramine in talc induced type 2 diabetes mellitus in Wistar rats.

Biomed Pharmacother 2018 Jan 6;97:652-655. Epub 2017 Nov 6.

Department of Biochemistry, Faculty of Science, King Abdul Azeez University, Kingdom of Saudi Arabia. Electronic address:

Evaluation of diphenhydramine in talc induced type 2 diabetes mellitus was done in Wistar rats. Oral administration of Talc (10mg/kg)carried out for 21days increased the levels of serum glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), serum creatinine, blood glucose, urea, uric acid and triglycerides (TGs), but when the animals were treated with diphenhydramine (DPH), the levels of the aforementioned biochemical parameters decreased significantly (p<0.0001). Read More

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http://dx.doi.org/10.1016/j.biopha.2017.10.085DOI Listing
January 2018
14 Reads

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

Biochem Biophys Res Commun 2018 01 31;495(1):92-97. Epub 2017 Oct 31.

Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou 510630, People's Republic of China.

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Read More

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http://dx.doi.org/10.1016/j.bbrc.2017.10.162DOI Listing
January 2018
2 Reads

Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-α correlating with high-mobility group box 1 expression in lipopolysaccharides-stimulated RAW 264.7 cells.

BMC Anesthesiol 2017 Oct 26;17(1):148. Epub 2017 Oct 26.

Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Background: Studies have found that propofol can inhibit endotoxin-induced monocyte-macrophages to produce various inflammatory factors. This study is to disclose whether the propofol affects the expression of high-mobility group box 1 (HMGB1) in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and the release of interleukin-6 (IL-6), 8 (IL-8) and tumor necrosis factor-α (TNF-α). Read More

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http://dx.doi.org/10.1186/s12871-017-0441-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658982PMC
October 2017
20 Reads