Abstract:
:The role of the functional substituents on the pyridinium ring of bisquaternary pyridinium compounds, mostly oximes, in exerting reversible and irreversible inhibition of binding of [3H]-N-methyl-4-piperidyl benzilate [( 3H]-4NMPB) to rat brain stem muscarinic receptors was studied. The drugs tested, i.e. HGG-42, HGG-12, HGG-52, HI-6, obidoxim, SAD-128 and TMB-4, could reversibly inhibit binding of [3H]-4NMPB, with the highest potency (KI = 1.7 - 6 microM) exhibited by analogs possessing hydrophobic substituents at position 3 or 4 of the pyridinium ring. Bisquaternary drugs possessing an oxime moiety at position 2, but not at position 4 of the pyridinium ring, could also induce about 30% reduction of maximal binding capacity (Bmax) (loss of muscarinic receptors) in addition to their reversible effect. Thus the structural correlates of the reversible and the irreversible effects of these drugs are different.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Kloog Y,Galron R,Balderman D,Sokolovsky Mdoi
10.1007/BF00292614subject
Has Abstractpub_date
1985-10-01 00:00:00pages
37-9issue
1eissn
0340-5761issn
1432-0738journal_volume
58pub_type
杂志文章abstract::This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a seco...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-013-1078-5
更新日期:2013-08-01 00:00:00
abstract::The effects of a single dose of ethanol on the metabolism and toxicity of chloroform administered to rats per os (p.o.), intraperitoneally (i.p.), or by inhalation (inh) at different doses were investigated. Rats that had been given either ethanol (2 g/kg) or vehicle (water) alone at 4 p.m. on the previous day were ch...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050131
更新日期:1994-01-01 00:00:00
abstract::The effects of six iv infusions of an emulsion containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) on the liver and testes were investigated in 40-day-old rats. Groups of five to six animals received the emulsion every other day in doses of 0, 5, 50 or 500 mg DEHP/kg body weight. Liver effects were studied by...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00348313
更新日期:1985-12-01 00:00:00
abstract::The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-m...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00316123
更新日期:1984-09-01 00:00:00
abstract::Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic dr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02454-1
更新日期:2019-06-01 00:00:00
abstract::To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O2/5% CO2 atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of t...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040100256
更新日期:2001-09-01 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::The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of D-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60 mg/L sodium arsenite (NaAsO2) through drinking wa...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02616-1
更新日期:2020-01-01 00:00:00
abstract::Alternative methods to detect non-genotoxic carcinogens are urgently needed, as this class of carcinogens goes undetected in the current testing strategy for carcinogenicity under REACH. A complicating factor is that non-genotoxic carcinogens act through several distinctive modes of action, which makes prediction of t...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1368-6
更新日期:2015-12-01 00:00:00
abstract:: ...
journal_title:Archives of toxicology
pub_type: 评论,信件
doi:10.1007/s00204-018-2310-0
更新日期:2018-11-01 00:00:00
abstract::Epidemiological and experimental studies have demonstrated the atherogenic effects of environmental toxicant arsenic and fluoride. Inflammatory mechanism plays an important role in the pathogenesis of atherosclerosis. The aim of the present study is to determine the effect of chronic exposure to arsenic and fluoride a...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-012-0803-9
更新日期:2012-06-01 00:00:00
abstract::The effect of 1-deamino-2-tyr(ethyl) oxytocin (dEtOT) upon peri- and postnatal development of the rat was studied in two experiments when administered between day 15 of pregnancy and the day of parturition. The investigation showed that dEtOT did not affect the pups at birth, that dEtOT caused a dose-related growth re...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00324786
更新日期:1985-09-01 00:00:00
abstract::Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031-4 μM in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytoto...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-011-0771-5
更新日期:2012-03-01 00:00:00
abstract::The immunotoxic potential of many classes of environmental contaminants has been well established in laboratory studies, with much attention being focussed on aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) congener...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050326
更新日期:1996-01-01 00:00:00
abstract::Certain esterase inhibitors such as O-(2-chloro-2,3,3-trifluorocyclobutyl) O-ethyl S-propyl phosphorothioate (KBR-2822) and phenylmethanesulfonyl fluoride (PMSF) cause exacerbation (promotion) of toxic and traumatic axonopathies. Although these chemicals are capable of inhibiting neuropathy target esterase (NTE), whic...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050473
更新日期:1998-01-01 00:00:00
abstract::Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials. To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives. The effects on cell viability, mitochondrial dehydrogenase, and proteog...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01977402
更新日期:1993-01-01 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::Many carcinogens and mutagens are electrophilic in nature and will react with nucleophilic sites in protein and nucleic acid. Determination of the extent of formation of these adducts of genotoxic agents with protein provides a practical method of monitoring human exposure and of determining the possible risk associat...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00296978
更新日期:1987-01-01 00:00:00
abstract::UDP-glucuronosyltransferases (UGTs) are involved in phase II conjugation reactions of xenobiotics and differences in their isoform activities result in interindividual kinetic differences of UGT probe substrates. Here, extensive literature searches were performed to identify probe substrates (14) for various UGT isofo...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-020-02765-8
更新日期:2020-08-01 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 use of nanotechnology is increasing exponentially, whereas the possible adverse health effects of engineered nanoparticles (NPs) are so far less known. Standardized mouse bioassay was used to study sensory and pulmonary irritation, airflow limitation, and inflammation potency of nanosized TiO(2). Single exposure (...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-011-0644-y
更新日期:2011-07-01 00:00:00
abstract::This study was performed to assess the relation between occupational exposure to N,N-dimethylformamide after an 8 h work shift in the acrylic fibre industry and its three biological markers N-methylformamide (NMFtotal), N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), and N-methylcarbamoyl adduct at haemoglobin (MCVal)....
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2219-7
更新日期:2018-07-01 00:00:00
abstract::Changes in the electrophysiologic activity of the rat sciatic nerve were examined after repeated dosing with either of two organophosphate insecticides, parathion, and trichlorfon. Although the parathion treated animals showed overt signs of systemic toxicity, there were no significant changes in any of the measured p...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00333896
更新日期:1983-03-01 00:00:00
abstract::The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040100264
更新日期:2001-10-01 00:00:00
abstract::The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00278645
更新日期:1989-01-01 00:00:00
abstract::The effect of pretreatment with cadmium (Cd) complexes on the distribution and accumulation of Cd in the liver and kidneys was examined for the Cd complexes that are reabsorbed site-selectively at the renal proximal tubules of rats. Cd was administered simultaneously with excess cysteine or as metallothionein (MT) and...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00297117
更新日期:1986-04-01 00:00:00
abstract::Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumole...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00364653
更新日期:1978-06-16 00:00:00
abstract::Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secreto...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040000174
更新日期:2000-12-01 00:00:00
abstract::Pregnane X receptor (PXR) is a nuclear receptor that plays a key regulatory role in xenobiotic metabolism in a ligand-dependent manner. Recently, ethanol was reported to be either an inducer or inhibitor of Cytochrome P450 (CYP) 3A expression. According to our recent microarray data, chronic ethanol upregulates the ex...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1268-9
更新日期:2015-04-01 00:00:00
abstract::Metabolism of carbaryl by rat liver and skin post-mitochondrial fraction has been measured in the presence and absence of cofactors to promote different metabolic pathways. The metabolic capacity was compared with the metabolism of carbaryl during percutaneous absorption in a static skin diffusion system using a varie...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01973722
更新日期:1991-01-01 00:00:00