Chemical Research in Toxicology最新文献_第8页

Refining the Amino Reactivity-Based Identification of Respiratory Sensitizers. 改进基于氨基反应性的呼吸致敏剂鉴定。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-06-16 Epub Date: 2025-05-29 DOI: 10.1021/acs.chemrestox.4c00545

Martin Simoneit, Helene Langer, Nadin Ulrich, Alexander Böhme

{"title":"Refining the Amino Reactivity-Based Identification of Respiratory Sensitizers.","authors":"Martin Simoneit, Helene Langer, Nadin Ulrich, Alexander Böhme","doi":"10.1021/acs.chemrestox.4c00545","DOIUrl":"10.1021/acs.chemrestox.4c00545","url":null,"abstract":"The sensitization of the respiratory tract may lead to various pulmonary diseases such as asthma. It can be triggered by the chemical reaction of organic electrophiles with nucleophiles of lung proteins with amino groups being of particular interest in this case. For assessing the dermal sensitization potential of chemicals, the direct peptide reactivity assay (DPRA) has become an OECD-accepted nonanimal test system. However, issues with the identification of known respiratory sensitizers such as isocyanates and anhydrides based on their amino reactivity in the DPRA have been reported. Hence, in this study the chemoassay employing glycine-para-nitroanilide (Gly-pNA) as model nucleophile is applied to eight iso(thio)cyanates, seven anhydrides, four dinitrobenzenes, one triazine, five acrylates, glutaraldehyde, and chloramine T to quantify their amino reactivity in terms of the second order rate constant kGly and the DPRA-like 24 h percent depletion DGly. A comparison of DGly with respective DPRA amino reactivity data (DDPRA) showed that in particular iso(thio)cyanates and anhydrides are substantially more reactive toward Gly-pNA. This can be rationalized by the unintentional and so far not considered reaction of the test compounds with the ammonium acetate buffer used for DPRA testing. A detailed analysis of this reaction includes half-lives and analytically determined adduct patterns and indicates that it can hamper the envisaged depletion of the DPRA amino nucleophile. Finally, the obtained log kGly values range from -3.73 to ≥ 4.52 and allow for an improved identification of respiratory sensitizers. Hence, the Gly-pNA chemoassay may serve as a nonanimal screening method as one part of a mechanism-informed integrated testing and assessment strategy for respiratory sensitizers.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1046-1060"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Review of the Protective Effects of Selenium against T-2 Toxin-Induced Toxicity. 硒对T-2毒素毒性的保护作用研究进展。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-06-16 Epub Date: 2025-05-21 DOI: 10.1021/acs.chemrestox.5c00095

Alexey A Tinkov, Anatoly V Skalny, Xiong Guo, Tatiana V Korobeinikova, Yujie Ning, Joao B T Rocha, Feng Zhang, Michael Aschner

{"title":"Review of the Protective Effects of Selenium against T-2 Toxin-Induced Toxicity.","authors":"Alexey A Tinkov, Anatoly V Skalny, Xiong Guo, Tatiana V Korobeinikova, Yujie Ning, Joao B T Rocha, Feng Zhang, Michael Aschner","doi":"10.1021/acs.chemrestox.5c00095","DOIUrl":"10.1021/acs.chemrestox.5c00095","url":null,"abstract":"The objective of the present study was to review the potential protective effects of Se against T-2 toxin-induced adverse effects in cartilage and other tissues as well as to discuss the potential molecular mechanisms by which Se counteracts T-2 toxicity. Laboratory studies demonstrate that Se attenuates T-2 toxin-induced chondrocyte death by inhibition of the mitochondrial pathway of apoptosis. Protective effects of Se against T-2 toxin-induced oxidative stress in chondrocytes are mediated by improvement of antioxidant selenoprotein expression, which is altered upon mycotoxin exposure. In addition to T-2 toxin-induced oxidative stress, Se treatment is associated with the inhibition of mycotoxin-induced chondrocyte ferroptosis. Along with prevention of chondrocyte damage, Se improves extracellular matrix (ECM) metabolism by the up-regulation of type II collagen and proteoglycans expression and inhibition of T-2 toxin-induced ECM degradation by matrix metalloproteinases. It is also noteworthy that part of the interactive effects between Se treatment and T-2 toxin exposure is mediated by epigenetic mechanisms, especially modulation of noncoding RNA expression. Recent evidence also shows that Se mitigates the toxic effects of the T-2 toxin in the liver, kidney, immune system, and other organs. Notably, a number of studies demonstrated that a Se deficiency aggravates the adverse effects of T-2 toxin exposure, supporting the notion of the protective effects of Se. However, the existing data were obtained in laboratory in vivo and in vitro models, and the potential therapeutic effects of Se supplementation in T-2 toxin-exposed human subjects have yet to be fully characterized.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"975-996"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.7 3区医学