6,809 results match your criteria Toxicity Sedative-Hypnotics


Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish.

Ecotoxicol Environ Saf 2022 Jun 28;238:113568. Epub 2022 Apr 28.

College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People's Republic of China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People's Republic of China. Electronic address:

Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. Read More

View Article and Full-Text PDF

Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood the Akt/p27 Signaling Pathway.

Biomed Environ Sci 2022 Apr;35(4):283-295

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China;NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.

Objective: Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established.

Methods: SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). Read More

View Article and Full-Text PDF

Analysis of drug adverse events in elderly patients based on the Japanese Adverse Drug Event Report Database.

J Clin Pharm Ther 2022 Apr 25. Epub 2022 Apr 25.

Laboratory of Regulatory Science, Faculty of Pharmacy, Musashino University, Nishi-tokyo, Japan.

What Is Known And Objective: Compared with the general adult population, pharmacokinetics and changes in drug responsiveness occur to a greater extent in the elderly. Interactions may occur between drugs used in combination to treat various diseases and may cause adverse events (AEs). We conducted a cross-sectional risk assessment of AEs in elderly patients based on information gathered from Japanese medical practices with the goal of obtaining information that will contribute to optimizing pharmacotherapy. Read More

View Article and Full-Text PDF

Midazolam Ameliorates Impairment of the Blood-Brain Barrier (BBB) Against LPS.

Neurotox Res 2022 Jun 22;40(3):751-762. Epub 2022 Apr 22.

Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.

Central nervous system (CNS) dysfunction induced by sepsis and pathogenic microbial infections is reported to be closely associated with increased permeability of the blood-brain barrier (BBB), which is mainly mediated by the stimulation of lipopolysaccharide (LPS) on inflammatory signaling. Midazolam is a novel sedative acting on the benzodiazepine receptor, which is recently reported to exert a neuroprotective effect by inhibiting inflammation. The present study will explore the potential repair capacity of Midazolam on LPS-induced damage to the BBB. Read More

View Article and Full-Text PDF

Propofol protects cardiomyocytes from doxorubicin-induced toxic injury by activating the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 signaling pathways.

Bioengineered 2022 Apr;13(4):9145-9155

Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Propofol offers important protective effects in ischemia/reperfusion-induced cardiomyocyte injury, but its specific mechanisms in doxorubicin (DOX)-induced cardiotoxicity have not been investigated. In this paper, we attempted to explore the effects of propofol on DOX-induced human cardiomyocyte injury and its related mechanisms. H9c2 cell viability was assessed by cell counting kit-8 and lactate dehydrogenase assay kit. Read More

View Article and Full-Text PDF

Efficacy of lipid emulsion therapy in treating cardiotoxicity from diphenhydramine ingestion: a review and analysis of case reports.

Clin Toxicol (Phila) 2022 May 16;60(5):550-558. Epub 2022 Feb 16.

Department of Emergency Medicine, Division of Medical Toxicology, Boston Children's Hospital, Boston, MA, USA.

Introduction: Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described. Read More

View Article and Full-Text PDF

Massive Nonfatal Hydroxychloroquine Ingestion in a Pediatric Patient.

J Emerg Med 2022 03 20;62(3):332-336. Epub 2022 Jan 20.

Division of Medical Toxicology, Department of Emergency Medicine, University of California-San Diego, San Diego, California.

Background: Hydroxychloroquine overdose is rare but potentially lethal. Hydroxychloroquine overdose symptoms are characterized by central nervous system toxicity, cardiac toxicity, and hypokalemia. Recommended treatment consists of epinephrine, high-dose diazepam, and careful potassium repletion. Read More

View Article and Full-Text PDF

Acute toxicity of disinfection by-products from chlorination of algal organic matter to the cladocerans Ceriodaphnia silvestrii and Daphnia similis: influence of bromide and quenching agent.

Environ Sci Pollut Res Int 2022 May 21;29(24):35800-35810. Epub 2022 Jan 21.

Department of Hydraulics and Sanitation, São Carlos School of Engineering, University of São Paulo, Av. Trabalhador São-Carlense, 400, São Carlos, , São Paulo, 13566-59, Brazil.

Algal organic matter (AOM) in water reservoirs is a worldwide concern for drinking water treatment; once it is one of the main precursors for disinfection by-products formation (DBPs). In this context, this study investigated the ecotoxicity of DBPs from chlorination of AOM to Ceriodaphnia silvestrii and Daphnia similis (Crustacea, Cladocera). The bioassays evaluated three scenarios, including the AOM extracted from Chlorella sorokiniana, the quenching condition used in the tests, and the DBPs formed after the chlorination of the two test waters with AOM (with and without bromide presence). Read More

View Article and Full-Text PDF

Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology.

Toxicol In Vitro 2022 Apr 14;80:105311. Epub 2022 Jan 14.

ScitoVation, 6 Davis Drive, Suite 146, Durham, NC 27709, United States of America.

There is increasing interest in using modern 'omics technologies, such as whole transcriptome sequencing, to inform decisions about human health safety and chemical toxicity hazard. High throughput methodologies using in vitro assays offer a path forward in reducing or eliminating animal testing. However, many aspects of these technologies need assessment before they will gain the trust of regulators and the public as viable alternative test methods for human health and safety. Read More

View Article and Full-Text PDF

Impurity Profiling and Identification of 2,6-Diisopropylphenol by HPLC Method and Raman Spectroscopy Method.

Adv Exp Med Biol 2021 ;1339:273-282

Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati, Andhra Pradesh, India.

Identification of 2,6-diisopropylphenol by Raman spectroscopy using the TruScan Raman spectrum is validated by specificity test and robustness. HPLC assay method is developed to detect the 2,6-diisopropylphenol and its impurities A = determination of 2,6-diisopropylphenol; its main impurities related compound A = 2,6-diisopropylphenyl isopropyl ether, related compound B = 2,6-diisopropylquinone, and related compound C = 3,3'-5,5'-tetraisopropyl diphenol; and unknown impurities done by HPLC method. Related compound A and C determination has been developed by normal phase HPLC; good resolution peak shapes have resulted from the peak results. Read More

View Article and Full-Text PDF
January 2022

Propofol rescues LPS-induced toxicity in HRT-8/SVneo cells via miR-216a-5p/TLR4 axis.

Arch Gynecol Obstet 2022 04 4;305(4):1055-1067. Epub 2022 Jan 4.

Department of Anesthesiology, Fujian Maternity and Child Health Hospital, 18 Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China.

Objective: The purpose of this study was to evaluate the effect of propofol on lipopolysaccharide (LPS)-induced toxicity in HTR-8/SVneo cells.

Methods: In this study, HTR-8/SVneo cells were induced by LPS. The cells were treated with different concentrations of propofol. Read More

View Article and Full-Text PDF

[Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice].

Sheng Li Xue Bao 2021 Dec;73(6):901-908

Center of Emergency and Trauma, First Affiliated Hospital of Army Medical University, Chongqing 400038, China.

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Read More

View Article and Full-Text PDF
December 2021

Dexmedetomidine modulates mitochondrial dynamics to protect against endotoxin-induced lung injury via the protein kinase C-ɑ/haem oxygenase-1 signalling pathway.

Biomarkers 2022 Mar 18;27(2):159-168. Epub 2022 Jan 18.

Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China.

Background: Endotoxin-induced acute lung injury (ALI) has a high mortality rate, and there are limited effective treatment options available. The aim of the present study was to identify if dexmedetomidine could regulate mitochondrial fusion and fission through the protein kinase C (PKC)-α/haem oxygenase (HO)-1 pathway to protect against endotoxin-induced ALI.

Materials And Methods: Dexmedetomidine was administered by intraperitoneal injection once daily for three days prior to induction of lung injury to mice. Read More

View Article and Full-Text PDF

Effects of ketamine, thiopental and their combination on the rat liver: A biochemical evaluation.

Adv Clin Exp Med 2022 Mar;31(3):285-292

Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Turkey.

Background: In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine.

Objectives: To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats.

Material And Methods: Male albino Wistar type rats received intraperitoneally (ip. Read More

View Article and Full-Text PDF

Propofol and Sevoflurane Anesthesia in Early Childhood Do Not Influence Seizure Threshold in Adult Rats.

Int J Environ Res Public Health 2021 11 24;18(23). Epub 2021 Nov 24.

II Department of Anesthesiology and Intensive Care, Medical University of Lublin, ul. Staszica 16, 20-081 Lublin, Poland.

Experimental studies have demonstrated that general anesthetics administered during the period of synaptogenesis may induce widespread neurodegeneration, which results in permanent cognitive and behavioral deficits. What remains to be elucidated is the extent of the potential influence of the commonly used hypnotics on comorbidities including epilepsy, which may have resulted from increased neurodegeneration during synaptogenesis. This study aimed to test the hypothesis that neuropathological changes induced by anesthetics during synaptogenesis may lead to changes in the seizure threshold during adulthood. Read More

View Article and Full-Text PDF
November 2021

The protective effect of high heme oxygenase-1 expression induced by propofol on the alveolar II type epithelial cells of rats with acute lung injury induced by oleic acid.

J Physiol Pharmacol 2021 Jun 3;72(3). Epub 2021 Dec 3.

Department of Anesthesiology, Tai'an Central Hospital, Tai'an, Shandong, China.

This study aimed to investigate the mechanism of propofol (PR) pretreatment inducing high heme oxygenase-1 (HO-1) expression to protect alveolar type II epithelial cells (AEC-II) in rats with acute lung injury (ALI) induced by oleic acid (OA). In this study, 32 male Sprague-Dawley rats (250 - 300 g) were randomly divided into four groups (n = 8 in each group) as follows: group C (the normal control group), the OA group (the oleic acid injury control group), the OA + PR group (the PR pretreatment group), and the OA + IX group (the zinc porphyrin IX pretreatment group). Arterial blood gases, bronchoalveolar lavage fluid (BALF), and serum pulmonary surfactant-associated protein A (SP-A) were measured in each group. Read More

View Article and Full-Text PDF

Mechanisms of respiratory depression induced by the combination of buprenorphine and diazepam in rats.

Br J Anaesth 2022 03 4;128(3):584-595. Epub 2021 Dec 4.

Université Paris-Saclay - CEA - CNRS - Inserm - BioMaps, Orsay, France.

Background: The safety profile of buprenorphine has encouraged its widespread use. However, fatalities have been attributed to benzodiazepine/buprenorphine combinations, by poorly understood mechanisms of toxicity. Mechanistic hypotheses include (i) benzodiazepine-mediated increase in brain buprenorphine (pharmacokinetic hypothesis); (ii) benzodiazepine-mediated potentiation of buprenorphine interaction with opioid receptors (receptor hypothesis); and (iii) combined effects of buprenorphine and benzodiazepine on respiratory parameters (pharmacodynamic hypothesis). Read More

View Article and Full-Text PDF

Corneal lesions related to an anesthetic mixture of medetomidine, midazolam, and butorphanol treatment in rats.

J Toxicol Sci 2021 ;46(12):561-568

Drug Safety and Pharmacokinetics Laboratories, Research Headquarters, Taisho Pharmaceutical Co., Ltd.

An anesthetic mixture of medetomidine, midazolam and butorphanol (MMB) has been recently used in laboratory animals. We observed corneal opacity in nephrectomized rats that had undergone two operations under MMB anesthesia at 4 and 5 weeks of age. To evaluate the features of this corneal opacity, ophthalmic examinations were conducted in 83 nephrectomized rats, and 8 representative animals with corneal opacity were evaluated histopathologically 4 weeks after operation. Read More

View Article and Full-Text PDF
January 2022

Anxiolytic, antidepressant and inhibitory effect on MAO isoenzymes by Bougainvillea glabra flower extract in rats.

Pak J Pharm Sci 2021 Sep;34(5(Supplementary)):1963-1968

Faculty of Pharmacy, Hamdard University, Karachi, Pakistan.

Main aim of current study was to determine the anxiolytic and antidepressant potential of Bougainvillea glabra Extract (BVE). The effects were investigated by using Open-Field-Test (OFT), Light-and-Dark Model (LD), Hole-Board (HB) and Forced-Swimming-Test (FST). Different doses for BVE were given to Wistar-Rats and compared with Control and Diazepam. Read More

View Article and Full-Text PDF
September 2021

Propofol enhances the lethality of cisplatin on liver cancer cells by up-regulating miR-195-5p.

Tissue Cell 2022 Feb 19;74:101680. Epub 2021 Nov 19.

Pharmacy Department, The People's Hospital of Xinchang, China. Electronic address:

Literatures have demonstrated that propofol can improve the efficacy of cisplatin, and miR-195 is implicated in the underlying mechanism concerning the anticancer effects of propofol. However, correlation between propofol and miR-195 has been little studied. This study clarified that propofol enhanced the inhibitory effect of cisplatin in liver cancer cells via miR-195-5p. Read More

View Article and Full-Text PDF
February 2022

CYP1A2 polymorphism may contribute to agomelatine-induced acute liver injury: Case report and review of the literature.

Medicine (Baltimore) 2021 Nov;100(45):e27736

The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Department of Psychiatry, Binhu District, Wuxi City, Jiangsu Province, China.

Rationale: Liver function monitoring is recommended when agomelatine is prescribed, although liver enzymes are not considered predictive biomarkers. Most patients present with acute liver injury, with only a few presenting with levels of liver enzymes that are over 30 times the upper limit of normal. The patient-specific risk factors that are associated with liver injury remain unclear. Read More

View Article and Full-Text PDF
November 2021

Role of IL-6/STAT3 pathway in mediating the protective effect of agomelatine against methotrexate-induced lung/intestinal tissues damage in rats.

Immunopharmacol Immunotoxicol 2022 Feb 12;44(1):35-46. Epub 2021 Nov 12.

Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.

Background: Methotrexate (MTX), an anticancer drug, has been linked to multiple organ toxicity. The drug-induced acute toxic symptoms can negatively affect the patient's commitment to the course of treatment.

Materials And Methods: This study aimed to investigate the mitigating action of agomelatine (Ago) against MTX-induced lung and intestinal toxicity. Read More

View Article and Full-Text PDF
February 2022

Neuropsychiatric effects of cannabis toxicity in the emergency department: A community-based study.

Am J Emerg Med 2022 Jun 3;56:375-377. Epub 2021 Nov 3.

Department of Emergency Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, United States of America; Spectrum Health - Michigan State University Emergency Medicine Residency Program, Grand Rapids, MI, United States of America. Electronic address:

View Article and Full-Text PDF

Suppression of apoptotic signaling in rat hepatocytes by non-dioxin-like polychlorinated biphenyls depends on the receptors CAR and PXR.

Toxicology 2021 12 4;464:153023. Epub 2021 Nov 4.

Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany. Electronic address:

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) represent a sub-group of persistent organic pollutants found in food, environmental samples and human and animal tissues. Promotion of pre-neoplastic lesions in rodent liver has been suggested as an indicator for a possible increased risk of liver cancer in humans exposed to NDL-PCBs. In rodent hepatocytes, suppression of DNA damage-triggered apoptosis is a typical mode of action of liver tumor promoters. Read More

View Article and Full-Text PDF
December 2021

Antinociceptive effects of flower extracts and the active fraction from Styrax japonicus.

J Ethnopharmacol 2022 Feb 27;284:114779. Epub 2021 Oct 27.

Department of Landscape Architecture, School of Design, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China; R&D Center for Aromatic Plants, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China. Electronic address:

Ethnopharmacological Relevance: Flowers from Styrax japonicus sieb. et Zucc. have been used as a Chinese folk medicine to alleviate pain such as toothache and sore throat. Read More

View Article and Full-Text PDF
February 2022

OGR1-dependent regulation of the allergen-induced asthma phenotype.

Am J Physiol Lung Cell Mol Physiol 2021 12 20;321(6):L1044-L1054. Epub 2021 Oct 20.

Department of Medicine, Division of Pulmonary and Critical Care Medicine & Center for Translational Medicine, Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Read More

View Article and Full-Text PDF
December 2021

Combination of antiseizure medications phenobarbital, ketamine, and midazolam reduces soman-induced epileptogenesis and brain pathology in rats.

Epilepsia Open 2021 12 23;6(4):757-769. Epub 2021 Oct 23.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Objective: Cholinergic-induced status epilepticus (SE) is associated with a loss of synaptic gamma-aminobutyric acid A receptors (GABA R) and an increase in N-methyl-D-aspartate receptors (NMDAR) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) that may contribute to pharmacoresistance when treatment with benzodiazepine antiseizure medication is delayed. The barbiturate phenobarbital enhances inhibitory neurotransmission by binding to a specific site in the GABA R to increase the open state of the channel, decrease neuronal excitability, and reduce glutamate-induced currents through AMPA/kainate receptors. We hypothesized that phenobarbital as an adjunct to midazolam would augment the amelioration of soman-induced SE and associated neuropathological changes and that further protection would be provided by the addition of an NMDAR antagonist. Read More

View Article and Full-Text PDF
December 2021

Targeting miRNAs with anesthetics in cancer: Current understanding and future perspectives.

Biomed Pharmacother 2021 Dec 12;144:112309. Epub 2021 Oct 12.

Faculty of Medicine, Tabriz University of Medical Sciences, Iran; Student Research Committee, Tabriz University of Medical Sciences, Iran.

Anesthetics are extensively used during cancer surgeries. The progression of cancer can be influenced by perioperative events such as exposure to general or local anesthesia. However, whether they inhibit cancer or act as a causative factor for metastasis and exert deleterious effects on cancer growth differs based on the type of cancer and the therapy administration. Read More

View Article and Full-Text PDF
December 2021

Combined Cardiopulmonary Assessments Using Impedance and Digital Implants in Conscious Freely Moving Cynomolgus Monkeys, Beagle Dogs, and Göttingen Minipigs: Pharmacological Characterization and Social Housing Effects.

Int J Toxicol 2021 12 6;40(6):530-541. Epub 2021 Oct 6.

7016Charles River Laboratories Laval, Quebec, Canada.

Respiratory monitoring, using impedance with implanted telemetry in socially housed animals, was not possible until the recent development of digital signal transmission. The objective of this study was to evaluate digital telemetry monitoring of cardiopulmonary parameters (respiratory rate, tidal volume, minute volume, electrocardiography (DII), systemic arterial blood pressure, physical activity, and body temperature) in conscious, single-housed, non-rodent species commonly used in toxicology studies following administration of positive/negative controls (saline, dexmedetomidine, morphine, amphetamine, and doxapram), and also, the effects of various social housing arrangements in untreated female and/or male cynomolgus monkeys, Beagle dogs, and Göttingen minipigs (n = 4 per species). Aggressions were observed in socially housed male minipigs, however, which prevented pair-housed assessments in this species. Read More

View Article and Full-Text PDF
December 2021

Iron foam coupled hydrolysis acidification for trichloroacetaldehyde treatment: Strengthening characteristics and mechanism.

Bioresour Technol 2021 Dec 28;342:126047. Epub 2021 Sep 28.

School of Environment, Tsinghua University, Beijing 100084, PR China.

This research studied transformative characteristics and enhanced mechanism of trichloroacetaldehyde (TCAL), one of chlorinated acetaldehydes (CAAs), by coupled-type iron foam enhanced hydrolysis acidification (HA) reactor. Main results were given that better dechlorination and aldehyde removal were achieved at this process than coupled-type iron foam enhanced HA, alone iron foam and HA reactor. The reasons were due to better strengthening effects of iron foam and HA, iron foam reduced TCAL toxicity to microbes caused an improvement of microbial activity, therefore, volatile fatty acids (VFAs) content and acetate acid (Ac) ratio were increased compared with HA. Read More

View Article and Full-Text PDF
December 2021