In vivo protection studies of bis-quaternary 2-(hydroxyimino)- N-(pyridin-3-yl) acetamide derivatives against sarin poisoning in mice.

Abstract:

:In vivo antidotal efficacy of new bis- quaternary 2-(hydroxyimino)- N-(pyridin-3yl) acetamide derivatives (HNK series), to counter multiples of lethal doses of nerve agent sarin (GB) and reactivation of acetylcholinesterase (AChE), was evaluated in Swiss albino mice. [Protection index PI; median lethal dose (LD50) of sarin with treatment/LD50 of sarin] was estimated, using 0.05, 0.10, and 0.20 LD50 as treatment doses of all the oximes with atropine against sarin poisoning. Dose-dependent time course study was conducted at 0.2, 0.4 and 0.8 LD50 dose of sarin for estimating maximum AChE inhibition. At optimized time (15 min), in vivo enzyme half inhibition concentration (IC50) was calculated. AChE reactivation efficacy of HNK series and pralidoxime (2-PAM) were determined by plotting shift of log IC50 doses. HNK-102 with atropine showed three fold higher PI compared to 2-PAM. In vivo IC50 of sarin for brain and serum AChE was found to be 0.87 LD50 (139.2 µg/kg) and 0.48 LD50 (77.23 µg/kg), respectively. Treatment with HNK-102 and HNK-111 (equal to their 0.20LD50) significantly reactivated sarin-intoxicated AChE ( p < 0.05) at 2× IC50 dose of sarin, compared to 2-PAM. The study revealed that HNK-102 oxime was three times more potent as antidote, for acute sarin poisoning compared to 2-PAM in vivo.

journal_name

Hum Exp Toxicol

authors

Swami D,Karade HN,Acharya J,Kumar P

doi

10.1177/0960327116637109

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

23-32

issue

1

eissn

0960-3271

issn

1477-0903

pii

0960327116637109

journal_volume

36

pub_type

杂志文章
  • Effects of concentration reduction and partial replacement of paraquat by diquat on human toxicity: a clinical survey.

    abstract::Paraquat poisoning was studied in 174 patients over a 12-month period when a new, low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v diquat ion; 63 cases) replaced the original high concentration paraquat product (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/096032719201100401

    authors: Yoshioka T,Sugimoto T,Kinoshita N,Shimazu T,Hiraide A,Kuwagata Y

    更新日期:1992-07-01 00:00:00

  • Ototoxicity of trichloroethylene in concentrations relevant for the working environment.

    abstract::Organic solvents can cause hearing loss themselves or promote noise-induced hearing loss. The objective of this study was to review the literature on the effects of low-level exposure to trichloroethylene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigati...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327108090267

    authors: Vyskocil A,Leroux T,Truchon G,Lemay F,Gagnon F,Gendron M,Viau C

    更新日期:2008-03-01 00:00:00

  • Homicidal poisoning by injection of methidathion: the first ever report.

    abstract:UNLABELLED:We present the first ever case of homicidal poisoning due to injection of methidathion, an organophosphate insecticide. CASE:A 4-month-old baby presented to the emergency department with chief complaints of unconsciousness and irregular respiration. A bitter odour and an injection site with a greenish blue ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327109348082

    authors: Ozdemir C,Kar H,Bilge Y,Batuk G,Batuk HI

    更新日期:2009-08-01 00:00:00

  • Effects of endothelin and nitric oxide on cardiac muscle functions in experimental septic shock model.

    abstract::We aimed to investigate the possible roles of nitric oxide (NO) and endothelin on the changes of cardiac muscle function in both hyper- and hypodynamic septic shock periods. Cecal ligation and puncture was performed in 50 Wistar albino rats to induce septic shock. Changes in atrium and right ventricle papillary muscle...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327115583363

    authors: Ozer EK,Iskit AB

    更新日期:2016-03-01 00:00:00

  • Cardiac biomarkers in a model of acute catecholamine cardiotoxicity.

    abstract::Coronary heart disease and in particular its most serious form - acute myocardial infarction (AMI) - represents the most common cause of mortality in developed countries. Better prognosis may be achieved by understanding the etiopathogenetic mechanisms of AMI. Therefore, a catecholamine model of myocardial injury, whi...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327109350665

    authors: Mladenka P,Hrdina R,Bobrovová Z,Semecky V,Vávrová J,Holecková M,Palicka V,Mazurová Y,Nachtigal P

    更新日期:2009-10-01 00:00:00

  • Derivatives of dehydrocrotonin, a diterpene lactone isolated from Croton cajucara: cytotoxicity in rat cultured hepatocytes and in V79 cells.

    abstract::Derivatives of dehydrocrotonin (DHC; Compound I) with different anti-ulcerogenic properties but less toxicity were produced by reducing the cyclohexenone moiety of DHC with NaBH4 (Compound II), reducing the cyclohexenone and lactone moieties with LiAlH4 (Compound III) and transforming the lactone moiety into an amide ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/0960327102ht246oa

    authors: Melo PS,Durán N,Haun M

    更新日期:2002-05-01 00:00:00

  • Effects of lutein and chlorophyll b on GSH depletion and DNA damage induced by cisplatin in vivo.

    abstract::Recent studies have proposed the use of low concentrations of phytochemicals and combinations of phytochemicals in chemoprevention to reduce cytotoxicity and simulate normal ingestion through diet. The purpose of the present study was to evaluate whether the DNA damage, chromosome instability, and oxidative stress ind...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327112468911

    authors: Serpeloni JM,Almeida MR,Mercadante AZ,Bianchi ML,Antunes LM

    更新日期:2013-08-01 00:00:00

  • Vulpinic acid, a lichen metabolite, emerges as a potential drug candidate in the therapy of oxidative stress-related diseases, such as atherosclerosis.

    abstract::Vulpinic acid, a lichen compound, has been shown to have many beneficial effects and its medicinal value increases day by day. As in atherosclerosis, endothelial damage is the basis of many diseases. The aim of this study is to investigate the effects of vulpinic acid against oxidative stress damage induced by hydroge...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327119833745

    authors: Sahin E,Dabagoglu Psav S,Avan I,Candan M,Sahinturk V,Koparal AT

    更新日期:2019-06-01 00:00:00

  • Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use.

    abstract::Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhanc...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章,评审

    doi:10.1191/0960327106het654oa

    authors: Ikegami F,Sumino M,Fujii Y,Akiba T,Satoh T

    更新日期:2006-08-01 00:00:00

  • Reliability of history of acetaminophen ingestion in intentional drug overdose patients.

    abstract::The objective of this study was to determine the reliability of denial of acetaminophen ingestion in intentional drug overdose patients. All intentional drug overdose patients admitted to an emergency department who were able to provide a history were included. A detailed history was obtained on names, timing and numb...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327110366784

    authors: Bentur Y,Lurie Y,Tamir A,Keyes DC,Basis F

    更新日期:2011-01-01 00:00:00

  • Recent advances in understanding transforming growth factor beta regulation of orofacial development.

    abstract::Members of the transforming growth factor (TGF) family have emerged as critical contributors to the choreography of cellular and tissue interactions underlying morphogenesis of the orofacial region. The TGFs beta, and their downstream effector molecules, the Smads, play a pivotal role in normal as well as abnormal dev...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章,评审

    doi:10.1191/0960327105ht492oa

    authors: Greene RM,Pisano MM

    更新日期:2005-01-01 00:00:00

  • Dose-dependent toxicity of diphenhydramine overdose.

    abstract:BACKGROUND:Diphenhydramine (DPHM) overdose is a frequent cause of acute poisoning. Although its clinical features are well known, information about the dose-dependent toxicity of DPHM is still scarce. The objective of this study was to investigate the dose-dependent toxicity of DPHM in patients with acute DPHM poisonin...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/096032700671040438

    authors: Radovanovic D,Meier PJ,Guirguis M,Lorent JP,Kupferschmidt H

    更新日期:2000-09-01 00:00:00

  • Effects of chronic manganese toxicity on tissue levels and urinary excretion of nicotinamide nucleotides in rats.

    abstract::Male rats were exposed to manganese sulphate i.p. daily for a period of four weeks to see its effects on tissue levels and urinary excretion of total nicotinamide nucleotides (TNN). Increased levels of TNN were observed in blood and brain while the levels were found to be decreased in liver. There was a progressive in...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/096032719401300503

    authors: Patel AB,Pandya AA

    更新日期:1994-05-01 00:00:00

  • Radiation hormesis--a remedy for fear.

    abstract::Personal reflections on radiation hormesis for the past 50 years are presented. The causes of ignoring and rejections of this phenomenon by international and national bodies and by radiation protection establishment are analyzed. The opposition against nuclear weapons and preparations for nuclear war was probably the ...

    journal_title:Human & experimental toxicology

    pub_type: 历史文章,杂志文章,评审

    doi:10.1177/0960327110363974

    authors: Jaworowski Z

    更新日期:2010-04-01 00:00:00

  • Dopamine and dobutamine reduce myocardial d-propoxyphene content in experimentally intoxicated rats.

    abstract::The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continuously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 microgr...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/096032719101000203

    authors: Pedersen CB,Strøm J,Angelo HR,Munksgaard A,Høgskilde S,Bredgaard Sørensen M

    更新日期:1991-03-01 00:00:00

  • Protective effects of melatonin and Glycyrrhiza glabra extract on ochratoxin A--induced damages on testes in mature rats.

    abstract::The effect of Glycyrrhiza glabra extract (GgE) as a natural antioxidant and melatonin (MEL) on ochratoxin A (OTA)-induced histopathological damages on the testes and oxidative stress was evaluated in male rats. The animals were assigned into four groups (n = 8) including control and test groups. The rats in control gr...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327110368416

    authors: Malekinejad H,Mirzakhani N,Razi M,Cheraghi H,Alizadeh A,Dardmeh F

    更新日期:2011-02-01 00:00:00

  • Sex-specific differences in the regulation of inducible nitric oxide synthase by bisphenol A in neutrophils.

    abstract::The aim of the study was to evaluate the effect of bisphenol A (BPA) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by neutrophils with regard to sex and nuclear factor-κB (NF-κB) pathway participation in this process. This study demonstrated that BPA intensifies the production o...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327118793188

    authors: Ratajczak-Wrona W,Nowak K,Garley M,Tynecka M,Jablonska E

    更新日期:2019-02-01 00:00:00

  • Toxicological features of deliberate self-poisonings.

    abstract:BACKGROUND:Deliberate self-poisoning (DSP) is a major health problem with increasing incidence mainly among young people. OBJECTIVE:To examine the clinical and toxicological characteristics of DSP, it is compared to unintentional (non-DSP) exposures and those characteristics which might be associated with increased to...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/0960327104ht454oa

    authors: Bentur Y,Raikhlin-Eisenkraft B,Lavee M

    更新日期:2004-07-01 00:00:00

  • DNA damage and methylation induced by organophosphate flame retardants: Tris(2-chloroethyl) phosphate and tris(1-chloro-2-propyl) phosphate in human peripheral blood mononuclear cells.

    abstract::Phosphorus flame retardants are a group of chemicals that are used to slow or prevent the spread of fire. These compounds have been detected in different environments including human organism. In the present study, we have investigated DNA-damaging potential and effect on DNA methylation of tris(2-chloroethyl) phospha...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327119839174

    authors: Bukowski K,Wysokinski D,Mokra K,Wozniak K

    更新日期:2019-06-01 00:00:00

  • The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids.

    abstract::1. This study investigated whether the reactive organohalogen gases perfluoroisobutene (PFIB) and phosgene, which cause death by overwhelming pulmonary oedema, affect the surfactant system or type II pneumocytes of rat lung. 2. The progression and type of pulmonary injury in Porton Wistar-derived rats was monitored ov...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/096032799678839554

    authors: Jugg B,Jenner J,Rice P

    更新日期:1999-11-01 00:00:00

  • Research into individual predisposition to develop acute rhabdomyolysis attributed to fenoverine.

    abstract::A xenobiotic, well tolerated by the majority of treated patients, can cause serious complications in patients with individual susceptibility. Based on the hypothesis that such a phenomenon may occur in rare cases of rhabdomyolysis attributed to fenoverine (DCI), we designed a protocol to look for a genetic predisposit...

    journal_title:Human & experimental toxicology

    pub_type: 临床试验,杂志文章

    doi:10.1177/096032719601501004

    authors: Jouglard J,Kozak-Ribbens G,de Haro L,Cozzone PJ

    更新日期:1996-10-01 00:00:00

  • Quercetin protects rat hepatocytes from oxidative damage induced by ethanol and iron by maintaining intercellular liable iron pool.

    abstract::Accumulating evidence has shown that ethanol-induced iron overload plays a crucial role in the development and progression of alcoholic liver disease. We designed the present study to investigate the potential protective effect of quercetin, a naturally occurring iron-chelating antioxidant on alcoholic iron overload a...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327113499168

    authors: Li Y,Deng Y,Tang Y,Yu H,Gao C,Liu L,Liu L,Yao P

    更新日期:2014-05-01 00:00:00

  • The effects of early life lead exposure on the expression of interleukin (IL) 1β, IL-6, and glial fibrillary acidic protein in the hippocampus of mouse pups.

    abstract::The present study was undertaken to investigate the effects of maternal lead (Pb) exposure on the expression of interleukin (IL) 1β, IL 6, and glial fibrillary acidic protein (GFAP) in hippocampus of mice offspring. Pb exposure initiated from the beginning of gestation to weaning. Lead acetate (PbAc) administered in d...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327114529451

    authors: Li N,Liu X,Zhang P,Qiao M,Li H,Li X,Zhang H,Yu Z

    更新日期:2015-04-01 00:00:00

  • Knockdown of TRIM24 suppresses growth and induces apoptosis in acute myeloid leukemia through downregulation of Wnt/GSK-3β/β-catenin signaling.

    abstract::Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular funct...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327120938845

    authors: Li C,Xin H,Shi Y,Mu J

    更新日期:2020-12-01 00:00:00

  • Combined therapy of gabapentin with pantoprazole exhibited better protective action against forestomach and pylorus ligation-induced gastric esophageal reflux disease in albino Wistar rats.

    abstract::The current study was undertaken to evaluate the effect of combined therapy of gabapentin and pantoprazole against forestomach and pylorus ligation-induced gastric esophageal reflux disease (GERD) in albino Wistar rats. Rats were randomly divided into five groups, each group consisting of six rats, fasted for 24 h, un...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327119893409

    authors: Arya P,Kaithwas G

    更新日期:2020-04-01 00:00:00

  • Changes of acetylcholinesterase activity after long-term exposure to sarin vapors in rats.

    abstract::In our study, rats were exposed to sarin vapors for 240 min at four different concentrations (0.30, 0.43, 0.58 and 0.82 microg/L) in a whole-body inhalation chamber. The acetylcholinesterase activity (AChE, EC 3.1.1.7) was measured in the whole blood, frontal cortex (FC), pontomedullar area (PM) and basal ganglia (BG)...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/0960327105ht539oa

    authors: Bartosova-Sevelova L,Bajgar J

    更新日期:2005-07-01 00:00:00

  • Scientific research related to calcium channel blockers poisoning: Bibliometric analysis in Scopus, 1968-2012.

    abstract:PURPOSE:Calcium channel blockers (CCBs) were the most common agents associated with a significant morbidity and mortality rate. The main objective of this study was to examine the publication pattern related to CCBs poisoning at the global level using bibliometric analysis of articles published in SciVerse Scopus onlin...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327115571768

    authors: Zyoud SH,Al-Jabi SW,Sweileh WM,Waring WS

    更新日期:2015-11-01 00:00:00

  • Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

    abstract:INTRODUCTION:Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondial...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327116661020

    authors: Karadas S,Aslan M,Ceylan MR,Sunnetcioglu M,Bozan N,Kara H,Demir H

    更新日期:2017-07-01 00:00:00

  • Rat alveolar and interstitial macrophages in the fibrosing stage following quartz exposure.

    abstract::Exposure to quartz induces pulmonary inflammation and development of fibrosis. In order to study the fibrosing process, we investigated morphology, function and phenotype of alveolar (AMs) and interstitial (IMs) macrophages at an early stage of fibrosis in rats. Rats were exposed by intratracheal instillations of 10 m...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1191/096032700678816124

    authors: Zetterberg G,Elmberger G,Johansson A,Lundahl J,Lundborg M,Sköld CM,Tornling G,Camner P,Eklund A

    更新日期:2000-07-01 00:00:00

  • Impact of pesticides residue and heavy metals on lipids and fatty acids composition of some seafoods of Red Sea (KSA).

    abstract::Seafood is considered by nutritionists to be a high source of omega 3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) which are involved in prevention of cardiovascular diseases. The aim of the present study is firstly to detect the presence of organochlorine pesticides and heavy metals in some fresh seafood of ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章

    doi:10.1177/0960327110396535

    authors: Al-Malki AL,Moselhy SS

    更新日期:2011-10-01 00:00:00