Abstract:
:Cyclohexylmethylphosphonofluoridate (cyclosarin) is a highly toxic organophosphate, which was shown to be rather resistant to conventional oxime therapy. To give more insight into the inhibition, reactivation and aging kinetics, human acetyl-(AChE) and butyrylcholinesterase (BChE) were inhibited by cyclosarin (k2 of 7.4 and 3.8 x 10(8) M(-1) min(-1), respectively; pH 7.4, 37 degrees C) and reactivated with obidoxime, pralidoxime and three experimental oximes. The new oxime HLö 7 (1-[[[4-aminocarbonyl)-pyridinio]-methoxy]-methyl]-2,4-bis-[ (hydroxyimino)methyl] pyridinium dimethanesulphonate) was shown to be superior to the other oximes. At oxime concentrations anticipated to be relevant in humans, obidoxime and pralidoxime were extremely weak reactivators of AChE. Aging velocity of BChE was almost fourfold higher compared to AChE (ka of 0.32 h(-1) and 0.08 h(-1), respectively). A substantial spontaneous reactivation was observed with AChE. These results support previous in vivo findings that obidoxime and pralidoxime are insufficient antidotes in cyclosarin poisoning. By contrast, HLö 7 was shown to be an extremely potent reactivator of human AChE and BChE, which supports its position as a broad-spectrum oxime.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Worek F,Eyer P,Szinicz Ldoi
10.1007/s002040050546subject
Has Abstractpub_date
1998-09-01 00:00:00pages
580-7issue
9eissn
0340-5761issn
1432-0738journal_volume
72pub_type
杂志文章abstract::The aryl hydrocarbon receptor (AHR) is known to mediate the cellular response to numerous xenobiotics including dioxin. Surprisingly AHR knockout mice provide evidence for the involvement of the AHR signalling cascade in estrogen regulated physiological functions of the female reproductive system. Several studies alre...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-012-0870-y
更新日期:2012-10-01 00:00:00
abstract::The excretion and biotransformation of [14C] 1,1-dichloroethylene (vinylidene chloride, VDC) after administration of a single oral dose has been investigated in female rats. Seventy-two hours after a dose of 0.5, 5.0, and 50.0 mg/kg, 1.26, 9.70, 16.47%, respectively, are exhaled as unchanged VDC, and 13.64, 11.35, 6.1...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00353707
更新日期:1979-07-11 00:00:00
abstract::A predictive test using mice for the identification of contact sensitizing chemicals was developed. Contact sensitizing activity is measured as a function of draining lymph node activation following application of test chemical. Experimental conditions for assessment of induced lymph node cell (LNC) responses have bee...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01974070
更新日期:1993-01-01 00:00:00
abstract::Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of th...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-2097-4
更新日期:2018-02-01 00:00:00
abstract::Amygdalin (D-mandelonitrile-beta-D-gentiobioside) is a cyanogenic glycoside claimed to show anti-cancer activity, sold under the incorrect name "Laetrile". For a sensible discussion of its alleged activity and its established toxicity it is necessary that its fate in the organism is known. The pharmacokinetics of amyg...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00347879
更新日期:1982-03-01 00:00:00
abstract::The effect of Co(NO3)2, CdSO4, NiSO4, ZnSO4, and HgCl2 (given repeatedly in subtoxic doses in the drinking water for 30 days) on rat liver monooxygenases was studied in experiments on male Wistar rats. The salts of Co, Cd, and Zn increased the activity of benzphetamine-N-demethylase, the content of cytochrome P-450 an...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00333421
更新日期:1985-01-01 00:00:00
abstract::With the development of nanotechnology, myriad types of novel materials have been discovered at the nanoscale, among which the most interesting material is graphene. However, the toxicity data available on graphene are extremely limited. In this study, we explored toxic response of commercially available graphene nano...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1303-x
更新日期:2015-09-01 00:00:00
abstract::Dulcin (DL), now banned, was once a widely used artificial sweetener. DL possesses an ureido group that is metabolized by direct glucuronidation in rabbit liver microsomes. Dulcin N-glucuronide (DNG) is the only type of ureido N-glucuronide known to date; ureido glucuronidation in humans has not been previously report...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-006-0138-5
更新日期:2007-03-01 00:00:00
abstract::During/after the BP/Deepwater Horizon oil spill, cleanup workers, fisherpersons, SCUBA divers, and coastal residents were exposed to crude oil and dispersants. These people experienced acute physiological and behavioral symptoms and consulted a physician. They were diagnosed with petroleum hydrocarbon poisoning and ha...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-015-1526-5
更新日期:2016-04-01 00:00:00
abstract::Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as pr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02389-7
更新日期:2019-03-01 00:00:00
abstract::The aim of this study was to investigate the electrophilic tissue burden (ETB) formation, assessed as covalent binding of the ultimate carcinogen benzo( a)pyrene diolepoxide (BaPDE) with cellular proteins, in liver, lung and heart, as well as with haemoglobin (Hb) following repeated exposure to binary mixtures of benz...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-003-0518-z
更新日期:2004-02-01 00:00:00
abstract::The treatment of poisoning by highly toxic organophosphorus compounds (nerve agents) is unsatisfactory. Until now, the efficacy of new potential antidotes has primarily been evaluated in animals. However, the extrapolation of these results to humans is hampered by species differences. Since oximes are believed to act ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050495
更新日期:1998-03-01 00:00:00
abstract::Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-020-02797-0
更新日期:2020-07-01 00:00:00
abstract::Clinical and electrophysiological examinations were performed on 12 patients with toxic neuropathy following accidental ingestion of alcohol polluted by triorthocresyl phosphate (TOCP). Concurrent PNS and CNS lesions were found in all patients. Two to three months after ingestion, five of them showed prevalent signs o...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00366186
更新日期:1980-02-01 00:00:00
abstract::Between 0.25-25 micrograms of an aqueous solution of either mercuric chloride or methyl mercuric acetate was injected directly into the sciatic nerve of 28 adult Wistar rats. The resultant pathological changes in the nerve were examined by teasing individual fibres and by light and electron microscopy. In most respect...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00310442
更新日期:1980-12-01 00:00:00
abstract::There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies t...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-001-0311-9
更新日期:2002-04-01 00:00:00
abstract::Etridiazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S-(5-ethoxy-1,2,4-thiadiazol-3-yl-methyl)-L-cysteine (ET-MA). Selective and sensitive analy...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF02098027
更新日期:1991-01-01 00:00:00
abstract::As Drosophila melanogaster occupies an important position within the test battery for mutagens and carcinogens, it is of interest to study the xenobiotics metabolism of this insect. Likewise, the genetic control of these important enzyme systems falls within this interest. Our attempt was to get new strains, which sho...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00316345
更新日期:1984-11-01 00:00:00
abstract::Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and S...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-2106-7
更新日期:2018-02-01 00:00:00
abstract::The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 mumol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00334632
更新日期:1989-01-01 00:00:00
abstract::A method is described for the determination of lorazepam plasma levels involving extraction from the sample and analysis of the intact lorazepam by electron capture gas-liquid chromatography. Using mass spectrometry it is demonstrated, that lorazepam shows a thermal rearrangement under gas chromatographic conditions. ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00293571
更新日期:1976-06-08 00:00:00
abstract::The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumpt...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-007-0209-2
更新日期:2007-11-01 00:00:00
abstract::Perfluoroalkyl acids are widely used in numerous industrial and commercial applications due to their unique physical and chemical characteristics. Although perfluorooctanoic acid (PFOA) is associated with hepatomegaly through peroxisome proliferator-activated receptor α (PPARα) activation, liver fat accumulation and c...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1322-7
更新日期:2015-09-01 00:00:00
abstract::In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050555
更新日期:1998-10-01 00:00:00
abstract::The rodenticide tetramethylenedisulfotetramine (TETS) is a potent convulsant (lethal dose in humans 7-10 mg) that is listed as a possible threat agent by the United States Department of Homeland Security. TETS has previously been studied in vivo for toxicity and in vitro in binding assays, with the latter demonstratin...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-2089-4
更新日期:2018-02-01 00:00:00
abstract::Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050192
更新日期:1995-01-01 00:00:00
abstract::3H-soman (specific activity 10 Ci/mMol), a potent irreversible cholinesterase inhibitor, was administered IV to mice in a dose of one LD-50, which corresponds to 0.25 mCi/mouse. Animals were sacrificed at 5 min, 2 h and 24 h, and whole body autoradiography was performed. High levels of radioactivity in lung and skin w...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00292616
更新日期:1985-10-01 00:00:00
abstract::The flavonol quercetin shows a wide range of effects in biological systems. We investigated whether quercetin exerts its proposed antioxidant properties via the antioxidant enzyme system. Quercetin in a concentration range from 5 to 100 microM decreased manganese superoxide dismutase, glutathione peroxidase, and coppe...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-003-0482-7
更新日期:2003-09-01 00:00:00
abstract::Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2170-7
更新日期:2018-04-01 00:00:00
abstract::N-Methyl-2-pyrrolidone (NMP) is a versatile organic solvent frequently used for surface cleaning such as paint stripping or graffiti removal. Liquid NMP is rapidly absorbed through the skin but dermal vapour phase absorption might also play an important role for the uptake of the solvent. This particular aspect was in...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-007-0230-5
更新日期:2008-01-01 00:00:00