自引率: 6.6%
被引量: 5462
通过率: 暂无数据
审稿周期: 1
版面费用: 暂无数据
国人发稿量: 18
投稿须知/期刊简介:
The Journal of Applied Toxicology is devoted to publishing original research theoretical and literature reviews relating to the toxicity of drugs and chemicals to living systems at the molecular cellular tissue and target organ level. This also encompasses teratogenesis carcinogenesis mutagenesis mechanistic technology pharmacokinetics environmental toxicology and environmental health (including epidemiological studies) in addition to analytical and method development studies. Papers dealing with in vitro techniques and alternatives to the use of animals are encouraged. Experiments on animals should conform to prevailing national or international standards of welfare care and handling of animals (eg NUH guidelines). Investigations in human volunteers and patients must indicate that relevant ethical reviews and guidelines have been followed including obtaining informed consent. Papers must be of clear scientific value and contribute to knowledge and advancement in toxicology. All papers will be independently refereed. Contributions must be in English and not have been published elsewhere except as abstracts at scientific meetings. Review articles will be published and prior consultation with one of the editors is reommended. Review articles will also be refereed. Authors must agree not to communicate the same material for publication elsewhere.
期刊描述简介:
The Journal of Applied Toxicology is devoted to publishing original research theoretical and literature reviews relating to the toxicity of drugs and chemicals to living systems at the molecular cellular tissue and target organ level. This also encompasses teratogenesis carcinogenesis mutagenesis mechanistic technology pharmacokinetics environmental toxicology and environmental health (including epidemiological studies) in addition to analytical and method development studies. Papers dealing with in vitro techniques and alternatives to the use of animals are encouraged. Experiments on animals should conform to prevailing national or international standards of welfare care and handling of animals (eg NUH guidelines). Investigations in human volunteers and patients must indicate that relevant ethical reviews and guidelines have been followed including obtaining informed consent. Papers must be of clear scientific value and contribute to knowledge and advancement in toxicology. All papers will be independently refereed. Contributions must be in English and not have been published elsewhere except as abstracts at scientific meetings. Review articles will be published and prior consultation with one of the editors is reommended. Review articles will also be refereed. Authors must agree not to communicate the same material for publication elsewhere.
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Concentration-dependent effects of the nerve agents cyclosarin and VX on cytochrome P450 in a HepaRG cell-based liver model.
The exposure to highly toxic organophosphorus (OP) compounds, including pesticides and nerve agents, is an ongoing medical challenge. OP can induce the uncontrolled overstimulation of the cholinergic system through inhibition of the enzyme acetylcholinesterase (AChE). The cytochrome P450 (CYP) enzymes in the liver play a predominant role in the metabolism of xenobiotics and are involved in the oxidative biotransformation of most clinical drugs. Previous research concerning the interactions between OP and CYP has usually focused on organothiophosphate pesticides that require CYP-mediated bioactivation to their active oxon metabolites to act as inhibitors of AChE. Since there has been little data available concerning the effect of nerve agents on CYP, we performed a study with cyclosarin (GF) and O-ethyl-S-[2-(diisopropylamino)-ethyl]-methylphosphonothioate (VX) by using a well-established, metabolically competent in vitro liver model (HepaRG cells). The inhibitory effect of the nerve agents GF and VX on the CYP3A4 enzyme was investigated showing a low CYP3A4 inhibitory potency. Changes on the transcription level of CYP and associated oxygenases were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the two nerve agent concentrations 250 nM and 250 μM. In conclusion, the results demonstrated various effects on oxygenase-associated genes in dependence of the concentration and the structure of the nerve agent. Such information might be of relevance for potential interactions between nerve agents, antidotes or other clinically administered drugs, which are metabolized by the affected CYP, for example, for the therapy with benzodiazepines, that are used for the symptomatic treatment of OP poisoning and that require CYP-mediated biotransformation.
被引量：- 发表：1970
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Epigenetic alternations in the SYP and DLG4 genes due to low-level methylmercury exposure during neuronal differentiation in vitro.
Methylmercury (MeHg) is an environmental toxin known to damage the central nervous system. When pregnant women ingest seafood, which may contain accumulated MeHg, fetal development may be affected. The embryonic period, a time of major epigenetic change, is susceptible to epigenetic disruptions due to chemical exposure. Therefore, understanding the molecular mechanism underlying MeHg's effects on neuronal development requires consideration of epigenetic factors. In this study, we investigated epigenetic modifications in the synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2-8 of neural differentiation. MeHg exposure significantly reduced the number of spikes observed on day 16 of differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. Additionally, MeHg treatment reduced acetyl histone H3 levels associated with transcriptional activity in the SYP gene while increasing histone H3 lysine 27 tri-methylation (H3K27me3) levels related to transcriptional repression. Conversely, regarding the DLG4 gene, MeHg exposure increased H3K27me3 levels. Differential changes in DNA methylation (high and low methylation states) were observed in the SYP and DLG4 genes due to MeHg exposure depending on CpG site position. In conclusion, this study suggests that epigenetic changes, particularly histone modifications, contribute to decreased MeHg exposure-induced SYP and DLG4 expression during neuronal differentiation.
被引量：- 发表：1970
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Toxicity of soil leaching liquor from coking plant in developmental zebrafish embryos/larvae model.
The coking industry in China is the largest coke supplier in the world. Contaminated soil in industrial areas poses a serious threat to human and ecosystems. Most of the studies investigated the toxicity of soil from coking plant on soil microorganisms, while the toxic effects of soil leaching liquor on aquatics are limited. In this study, the composition of soil leaching liquor from a coking plant in Taiyuan (TY) was analyzed, and the developmental toxicity on zebrafish was evaluated. The results showed that a total of 91 polycyclic aromatic hydrocarbons were detected in the leaching liquor, followed by phenols and benzene series. The leaching liquor induced developmental impairment in zebrafish larvae, including delayed incubation, deficits in locomotor behavior, vascular and cardiac dysplasia, and impaired neurodevelopment. The results of metabolomics analysis showed that TY soil leaching liquor induced significant metabolic profile disturbances in zebrafish embryos/larvae. The developmental toxicity of the leaching liquor metabolic disorders may be associated with the leaching liquor-induced abnormalities in zebrafish embryonic development. Metabolic pathways were identified by arginine and proline metabolism, phosphotransferase system, starch and sucrose metabolism, steroid biosynthesis, beta-alanine metabolism, and nucleotide metabolism pathways.
被引量：- 发表：1970
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Non-chemical stresses do not strongly induce male offspring in Daphnia magna ascertained using the short-term juvenile hormone activity screening assay.
Juvenile hormone (JH), together with ecdysone, regulates molting, metamorphosis, growth, and reproduction in arthropods. The effects of its analogs used as insecticides on nontarget species are of concern. Since JH and JH analogs (JHAs) induce male offspring in daphnids, which generally reproduce by parthenogenesis, short-term JH activity screening assay (JHASA) using the male offspring ratio as an endpoint has been developed as a detection method for JHA. However, the production of male offspring is also induced by environmental stresses such as temperature, short-day length, overcrowding, and food limitation. Thus, it is vital to prevent non-chemical stresses from inducing male offspring during the test to detect chemicals with potential JH activity accurately. Therefore, we investigated the effects of temperature (low and high), hardness, high density with low feeding, and day length on male production utilizing JHASA. Male offspring were not strongly induced by any stresses in JHASA, although the male ratios of 4-12% were observed in the preculture under high density (≥70 daphnid/L) and constant darkness. The Clone A strain was relatively more sensitive to high density and day length compared with the strain from National Institute for Environmental Studies (NIES). The selection of strains that rarely produce males under non-chemical stresses and finding the culturing conditions for each strain appropriate for not-inducing male offspring are recommended to control and prevent male offspring induction during JHASA.
被引量：- 发表：1970
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90-day oral toxicity study in rats of a protein-rich powder derived from Xanthobacter sp. SoF1.
Xanthobacter sp. SoF1 (SoF1) is an autotrophic hydrogen-oxidizing bacteria that produces protein-rich biomass and has potential to be an alternative protein source that is more environmentally sustainable than animal and plant derived proteins. A protein-rich powder derived from SoF1 was the test material in a 90-day repeated-dose oral toxicity study to explore major toxic effects, demonstrate target organs, and provide an estimate of a no-observed-adverse-effect level (NOAEL). Daily doses of 0 (vehicle only), 375, 750, and 1500 mg/kg bw/day of the test material were administered by gavage to 10 Han:WIST rats/sex/group. An additional group was administered 1290 mg/kg bw/day whey protein concentrate as positive control. No treatment-related adverse effects were observed, and no target organs were determined after 90/91 days of consecutive administration of the test item. A NOAEL of 1500 mg/kg bw/day was determined.
被引量：- 发表：1970
