Clinical ToxicologyPub Date : 2024-05-01Epub Date: 2024-06-14DOI: 10.1080/15563650.2024.2361879
Gabriele Horn, Tobias Demel, Simone Rothmiller, Niko Amend, Franz Worek
{"title":"The influence of the model pesticides parathion and paraoxon on human cytochrome P450 and associated oxygenases in HepaRG cells.","authors":"Gabriele Horn, Tobias Demel, Simone Rothmiller, Niko Amend, Franz Worek","doi":"10.1080/15563650.2024.2361879","DOIUrl":"10.1080/15563650.2024.2361879","url":null,"abstract":"<p><strong>Introduction: </strong>Intentional and unintentional organophosphorus pesticide exposure is a public health concern. Organothiophosphate compounds require metabolic bioactivation by the cytochrome P450 system to their corresponding oxon analogues to act as potent inhibitors of acetylcholinesterase. It is known that interactions between cytochrome P450 and pesticides include the inhibition of major xenobiotic metabolizing cytochrome P450 enzymes and changes on the genetic level.</p><p><strong>Methods: </strong>In this <i>in vitro</i> study, the influence of the pesticides parathion and paraoxon on human cytochrome P450 and associated oxygenases was investigated with a metabolically competent cell line (HepaRG cells). First, the viability of the cells after exposure to parathion and paraoxon was evaluated. The inhibitory effect of both pesticides on cytochrome P450 3A4, which is a pivotal enzyme in the metabolism of xenobiotics, was examined by determining the dose-response curve. Changes on the transcription level of 92 oxygenase associated genes, including those for important cytochrome P450 enzymes, were evaluated.</p><p><strong>Results: </strong>The exposure of HepaRG cells to parathion and paraoxon at concentrations up to 100 µM resulted in a viability of 100 per cent. After exposure for 24 hours, pronounced inhibition of cytochrome P450 3A4 enzyme activity was shown, indicating 50 per cent effective concentrations of 1.2 µM (parathion) and 2.1 µM (paraoxon). The results revealed that cytochrome P450 involved in parathion metabolism were significantly upregulated.</p><p><strong>Discussion: </strong>Relevant changes of the cytochrome P450 3A4 enzyme activity and significant alteration of genes associated with cytochrome P450 suggest an interference of pesticide exposure with numerous metabolic processes. The major limitations of the work involve the use of a single pesticide and the <i>in vitro</i> model as surrogate to human hepatocytes.</p><p><strong>Conclusion: </strong>The data of this study might be of relevance after survival of acute, life-threatening intoxications with organophosphorus compounds, particularly for the co-administration of drugs, which are metabolized by the affected cytochrome P450.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"288-295"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316894","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}
Clinical ToxicologyPub Date : 2024-05-01Epub Date: 2024-05-23DOI: 10.1080/15563650.2024.2347514
Damilola Idowu, Kevin Ezema, Justin Corcoran, Andrew Farkas
{"title":"The predictive value of heart rate in determining clinical course after a bupropion overdose.","authors":"Damilola Idowu, Kevin Ezema, Justin Corcoran, Andrew Farkas","doi":"10.1080/15563650.2024.2347514","DOIUrl":"10.1080/15563650.2024.2347514","url":null,"abstract":"<p><strong>Introduction: </strong>Bupropion is a popular antidepressant due to its favorable side effect profile and indications for smoking cessation and weight loss. Due to the possibility of delayed onset seizure and other adverse outcomes after bupropion overdose, patients are often observed for periods of 12-24 hours following suspected ingestion. Tachycardia is a clinical predictor that holds promise in differentiating cases at risk for seizures from low-risk cases that do not require prolonged observation. This study assessed whether heart rate within the first eight hours of presentation can identify cases that do not require extended observation.</p><p><strong>Methods: </strong>This is a retrospective cohort study of all supra-therapeutic bupropion cases from two hospital systems between 2010 and 2022.</p><p><strong>Results: </strong>Data from 216 charts were included. Seizures, hypotension, and dysrhythmias occurred in 19 percent (<i>n</i> = 41), 1.4 percent (<i>n</i> = 3), 0.9 percent (<i>n</i> = 2) respectively. One patient died. Delayed adverse effects were rare (<i>n</i> = 4); they occurred from 14 hours to 28 hours post-ingestion. Maximum heart rate in eight hours was associated with a risk of adverse outcomes. (odds ratio, 1.07; 95 percent confidence interval: 1.05 to 1.09; <i>P <</i> 0.001). An eight hour maximum heart rate threshold of 104 beats/minute had a negative predictive value of 100 percent (95 percent confidence interval: 96.7 percent to 100 percent) for the occurrence of delayed adverse effects. All patients with delayed effects had tachycardia within five hours of emergency department arrival.</p><p><strong>Discussion: </strong>Delayed adverse outcomes of seizures, hypotension, dysrhythmia, and death were uncommon in this cohort. Heart rate during the first eight hours of observation performs reliably as a screening test to identify patients at low risk for delayed adverse outcomes. This study is limited by its retrospective nature, the inability to ascertain time of ingestion for most cases and the lack of confirmatory laboratory testing.</p><p><strong>Conclusion: </strong>This study supports the use of an eight hour observation period when there are no other clinical signs of toxicity to warrant admission and if no co-ingestion or administration of substances that mask tachycardia are present.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"296-302"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080855","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}
Alice Burgess, Hannah L. Hays, Jaahnavi Badeti, Henry A. Spiller, Natalie I. Rine, Christopher E. Gaw, Kele Ding, Gary A. Smith
{"title":"Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to America’s Poison Centers","authors":"Alice Burgess, Hannah L. Hays, Jaahnavi Badeti, Henry A. Spiller, Natalie I. Rine, Christopher E. Gaw, Kele Ding, Gary A. Smith","doi":"10.1080/15563650.2024.2340115","DOIUrl":"https://doi.org/10.1080/15563650.2024.2340115","url":null,"abstract":"Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydroc...","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"22 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831124","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}
Namkee G. Choi, Bryan Y. Choi, C. Nathan Marti, S. David Baker
{"title":"Intentional benzodiazepine poisoning in older adults reported to United States Poison Centers","authors":"Namkee G. Choi, Bryan Y. Choi, C. Nathan Marti, S. David Baker","doi":"10.1080/15563650.2024.2334828","DOIUrl":"https://doi.org/10.1080/15563650.2024.2334828","url":null,"abstract":"Despite known contraindications, benzodiazepines are frequently prescribed for older adults. This study utilizes poison control center data on benzodiazepine-involved cases aged 50 and above to com...","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"155 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831450","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}
Samanta M. Zwaag, Claudine C. Hunault, Dylan W. de Lange
{"title":"Predicting the outcome in poisoned patients: look at the past!","authors":"Samanta M. Zwaag, Claudine C. Hunault, Dylan W. de Lange","doi":"10.1080/15563650.2024.2334820","DOIUrl":"https://doi.org/10.1080/15563650.2024.2334820","url":null,"abstract":"When predicting future events, we often rely on analyzing past occurrences and projecting them forward. This methodology is crucial in various fields, including toxicology, in which predicting outc...","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"38 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831116","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}
{"title":"An in vitro study of metformin adsorption to activated charcoal","authors":"Yoshinori Tomoda, Masahiro Kobayashi","doi":"10.1080/15563650.2024.2338556","DOIUrl":"https://doi.org/10.1080/15563650.2024.2338556","url":null,"abstract":"Metformin is a biguanide used to manage patients with type 2 diabetes mellitus. However, metabolic acidosis with an elevated lactate concentration and death caused by metformin overdoses are toxico...","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"31 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636124","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}
{"title":"Response to Özdemir O on “Kounis syndrome due to remdesivir allergy”","authors":"Eirini Beneki, Kyriakos Dimitriadis, Alexandros Antonopoulos, Konstantina Aggeli, Konstantinos Tsioufis","doi":"10.1080/15563650.2024.2340113","DOIUrl":"https://doi.org/10.1080/15563650.2024.2340113","url":null,"abstract":"Published in Clinical Toxicology (Ahead of Print, 2024)","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630469","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}
{"title":"Increasing severity of medical outcomes and associated substances in cases reported to United States poison centers","authors":"Rita Farah, Ryan J. Cole, Christopher P. Holstege","doi":"10.1080/15563650.2024.2337897","DOIUrl":"https://doi.org/10.1080/15563650.2024.2337897","url":null,"abstract":"Poison centers provide free expert recommendations on the treatment of a wide variety of toxicological emergencies. Prior studies have called attention to the increasing complexity of cases reporte...","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"2012 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613561","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}
Yamile Sierra-Gordillo, Elkin Peñaranda-Contreras, Margarita M. Gomez Arbeláez, Paula A. Moreno-Lucero
{"title":"Toxic epidermal necrolysis associated with the use of levetiracetam","authors":"Yamile Sierra-Gordillo, Elkin Peñaranda-Contreras, Margarita M. Gomez Arbeláez, Paula A. Moreno-Lucero","doi":"10.1080/15563650.2024.2333810","DOIUrl":"https://doi.org/10.1080/15563650.2024.2333810","url":null,"abstract":"Published in Clinical Toxicology (Ahead of Print, 2024)","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":"6 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582188","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}