Abstract：
:Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce selectively the expression of CYP2A5 while expression of other CYPs is decreased. In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole (4Me; 0.1-20 mM) and 4-iodopyrazole (4-I; 0.1-5.0 mM). PYR and its derivatives increased coumarin 7-hydroxylase activity, with 4-1 and 4-OH being the strongest inducers, by 114-fold and 41-fold, respectively. However, only 4-1 treatment increased markedly the CYP2A5 protein content. CYP2B9/10-mediated pentoxyresorufin O-deethylase activity (PROD) was decreased by 80% by 4-Me and 4-1, and by 50% by 4-OH while PYR had no marked effect. PYR and 4-Me increased 2- to 3-fold the CYPA1/2-mediated ethoxyresorufin O-deethylase activity (EROD) while 4-OH and 4-1 had no marked effect on this enzyme. The time of exposure markedly affected the inducibility of 4-OH such that induction was 7-fold stronger when it was added to the incubation medium 24 h after the isolation of hepatocytes compared to exposure 3 h after their isolation. Cimetidine prevented the induction of coumarin 7-hydroxylase activity by PYR and 4-OH by 46 and 74%, respectively indicating that their effects on the expression of CYP2A5 are, at least partly, mediated via their metabolites. The data demonstrate that the regulation of CYP2A5 is different from other monooxygenases and that the effects of pyrazole and its derivatives are different in vivo and in vitro. Also, the timing of exposure markedly affects the inducibility of 4-OH in hepatocytes.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Kojo A,Viitala P,Pasanen M,Pelkonen O,Raunio H,Juvonen Rdoi
10.1007/s002040050511subject
Has Abstractpub_date
1998-05-01 00:00:00pages
336-41issue
6eissn
0340-5761issn
1432-0738journal_volume
72pub_type
杂志文章abstract：:To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (<0.5 ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1408-2
更新日期：2015-11-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact inhibition ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0601-0
更新日期：2005-01-01 00:00:00
abstract：:Possible induction of chromosomal aberrations and/or sister chromatid exchanges by astemizole was studied in vitro on human lymphocytes. In vivo chromosomal damage was assessed by a micronucleus test on rats and a dominant lethal test on both male and female mice. All these tests yielded negative results for astemizol...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00373399
更新日期：1982-07-01 00:00:00
abstract：:Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01973682
更新日期：1993-01-01 00:00:00
abstract：:Sulfur dioxide (SO2) is a common air pollutant, and inhaled SO2 in airway epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite), which are toxic to the respiratory system and related to the exacerbation of asthma. To investigate the effects of SO2 derivatives on the expressions of asthma rela...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0212-7
更新日期：2007-12-01 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：:The US Environmental Protection Agency's ToxCast program has generated toxicity data for thousands of chemicals but does not adequately assess potential neurotoxicity. Networks of neurons grown on microelectrode arrays (MEAs) offer an efficient approach to screen compounds for neuroactivity and distinguish between com...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02636-x
更新日期：2020-02-01 00:00:00
abstract：:The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated le...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00317980
更新日期：1983-01-01 00:00:00
abstract：:Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and de...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-015-1633-3
更新日期：2015-12-01 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：: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：:Spin trapping in vivo was first achieved in the author's laboratory and is shown to be a feasible method for demonstrating that highly reactive free radical intermediates are generated in the tissues of intact animals as a result of the exposure to certain toxic compounds and to ionizing radiation. The method is based...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/BF00296966
更新日期：1987-01-01 00:00:00
abstract：:This review provides a compendium of the results of genotoxicity and carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one carcinogen...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-011-0659-4
更新日期：2011-10-01 00:00:00
abstract：:The pregnancy outcomes of 109 women who were intoxicated during pregnancy due to excessive amounts of drugs and other agents were studied. Seventy per cent of the women attempted suicide, and the intoxication in 78% of all cases was caused by drugs. The stillbirth rate (4%) was higher than that in previous and subsequ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316249
更新日期：1988-08-01 00:00:00
abstract：:Rhabdomyolysis has been reported in patients who abuse synthetic cannabinoids. However, no studies have yet assessed whether these cases reflect the direct cytotoxicity of synthetic cannabinoids on skeletal muscle, a possibility that the present study sought to address. Specifically, this study investigated the cytoto...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02944-7
更新日期：2020-11-10 00:00:00
abstract：:Cholestasis underlies one of the major manifestations of drug-induced liver injury. Drug-induced cholestatic liver toxicity is a complex process, as it can be triggered by a variety of factors that induce 2 types of biological responses, namely a deteriorative response, caused by bile acid accumulation, and an adaptiv...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-019-02437-2
更新日期：2019-05-01 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：:Regarding the potential impact of traffic-born air pollutants on public health, in recent years attention has increasingly been focused on the possible effects on the cardiovascular system. In order to investigate this problem further, the influence of long-term exhaust gas exposure on rats has been studied. One hundr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00332390
更新日期：1981-07-01 00:00:00
abstract：:This review summarises the current state of knowledge regarding the physiology and control of production of thyroid hormones, the effects of chemicals in perturbing their synthesis and release that result in thyroid cancer. It does not consider the potential neurodevelopmental consequences of low thyroid hormones. The...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-020-02961-6
更新日期：2021-01-05 00:00:00
abstract：:Nephrotoxicity is a major side effect of cisplatin in chemotherapy. Pathologically, cisplatin nephrotoxicity is characterized by cell injury and death in renal tubules. The research in the past decade has gained significant understanding of the cellular and molecular mechanisms of tubular cell death, revealing a centr...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-014-1239-1
更新日期：2014-06-01 00:00:00
abstract：:Selenium (Se) is an essential dietary component for animals including humans and is regarded as a protective agent against cancer. Although the mode of anticancer action of Se is not fully understood yet, several mechanisms, such as antioxidant protection by selenoenzymes, specific inhibition of tumor cell growth by S...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-010-0595-8
更新日期：2010-12-01 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：:Cadmium, copper and zinc have been determined in kidney cortex, kidney medulla and liver from 51 cadmium-polluted and 122 nonpolluted autopsied subjects. Liver cadmium and zinc were significantly higher in the cadmium-polluted subjects than in the nonpolluted subjects. Kidney cadmium, copper and zinc were lower in the...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316211
更新日期：1987-04-01 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 first withdrawal of certain polybrominated diphenyl ethers flame retardants from the US market occurred in 2004. Since then, use of brominated non-PBDE compounds such as bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in commercial formulations has incr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-015-1489-6
更新日期：2016-03-01 00:00:00
abstract：:In a previous study, we showed that bisphenol A (BPA) had oestrogen-like effects in bird embryos, causing malformations of the oviducts in Japanese quail (Coturnix japonica) and feminisation of the left testis in chicken (Gallus domesticus). In this study, uptake and distribution of BPA and tetrabromobisphenol A (TBBP...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040100277
更新日期：2001-12-01 00:00:00
abstract：:Purified phenobarbital-induced rat liver cytochrome P-450 was incorporated in a reconstituted system containing NADPH-cytochrome P-450 reductase, dilauroyl phosphatidyl choline and sodium cholate. This system was added to organ cultures of limb buds from mouse embryos on day 11 of gestation. Cyclophosphamide (100 micr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00293687
更新日期：1988-01-01 00:00:00
abstract：:Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0586-8
更新日期：2004-11-01 00:00:00
abstract：:In vivo screening methods for detection of thyroid function modulators are now under development in many research laboratories. We assessed the applicability of the Hershberger assay protocol to screen for thyroid function modulators. In experiment 1, castrated male BrlHan WIST@Jcl (GALAS) rats were administered a pot...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-005-0677-1
更新日期：2005-11-01 00:00:00
abstract：:Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the org...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02547-x
更新日期：2019-10-01 00:00:00
