Effects of species of origin and mode of induction of microsomes on carbamazepine-induced cell toxicity

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2024-07-01 DOI:10.1016/j.vascn.2024.107536
Abdelbaset A. Elzagallaai , Awatif M. Abuzgaia , Michael J. Rieder
{"title":"Effects of species of origin and mode of induction of microsomes on carbamazepine-induced cell toxicity","authors":"Abdelbaset A. Elzagallaai ,&nbsp;Awatif M. Abuzgaia ,&nbsp;Michael J. Rieder","doi":"10.1016/j.vascn.2024.107536","DOIUrl":null,"url":null,"abstract":"<div><p>Standardization and validation of <em>in vitro</em> drug metabolism is essential for pre-clinical drug development as well as for <em>in vitro</em> toxicity assays including the lymphocyte toxicity assay (LTA) and the <em>in vitro</em> platelet toxicity assay (iPTA). Use of isolated liver microsomes (MIC) in <em>in vitro</em> testing has been utilized for a long time; however, the effect of species of origin and induction agents on the metabolic capacities of MIC is not adequately evaluated. In this study we investigated the impact of species of origin and induction agent on the capacity of MICs to bioactivate carbamazepine (CBZ) using cytotoxicity as a gross endpoint to measure the levels of cytotoxic metabolites generated by each type of MICs. Jurkat E6.1 cell line was used and MICs from human, rat, mouse, minipig and rabbit origin as well as rat MICs that is either non-induced or induced by phenobarbitone (PHB), dexamethasone (DEXA), 3-methylcholanthrene (3MC), clofibrate (CLOF) and isoniazid (INH) were investigated. MICs from minipig and rat MICs induced with 3MC exhibited the highest capacity to produce cytotoxic metabolites of CBZ. These findings will help optimize and standardize <em>in vitro</em> toxicity assays and provide guidance to pre-clinical investigation of drugs.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological and toxicological methods","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1056871924000467","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Standardization and validation of in vitro drug metabolism is essential for pre-clinical drug development as well as for in vitro toxicity assays including the lymphocyte toxicity assay (LTA) and the in vitro platelet toxicity assay (iPTA). Use of isolated liver microsomes (MIC) in in vitro testing has been utilized for a long time; however, the effect of species of origin and induction agents on the metabolic capacities of MIC is not adequately evaluated. In this study we investigated the impact of species of origin and induction agent on the capacity of MICs to bioactivate carbamazepine (CBZ) using cytotoxicity as a gross endpoint to measure the levels of cytotoxic metabolites generated by each type of MICs. Jurkat E6.1 cell line was used and MICs from human, rat, mouse, minipig and rabbit origin as well as rat MICs that is either non-induced or induced by phenobarbitone (PHB), dexamethasone (DEXA), 3-methylcholanthrene (3MC), clofibrate (CLOF) and isoniazid (INH) were investigated. MICs from minipig and rat MICs induced with 3MC exhibited the highest capacity to produce cytotoxic metabolites of CBZ. These findings will help optimize and standardize in vitro toxicity assays and provide guidance to pre-clinical investigation of drugs.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
微粒体的来源种类和诱导方式对卡马西平诱导的细胞毒性的影响
体外药物代谢的标准化和验证对于临床前药物开发以及体外毒性检测(包括淋巴细胞毒性检测(LTA)和体外血小板毒性检测(iPTA))至关重要。在体外测试中使用分离的肝脏微粒体(MIC)由来已久,但尚未充分评估来源物种和诱导剂对 MIC 代谢能力的影响。在本研究中,我们以细胞毒性为总终点,测量了各类 MIC 产生的细胞毒性代谢物的水平,从而研究了来源种类和诱导剂对 MIC 生物活化卡马西平(CBZ)能力的影响。我们使用了 Jurkat E6.1 细胞系,并研究了来自人、大鼠、小鼠、迷你猪和兔子的 MICs,以及未被苯巴比妥(PHB)、地塞米松(DEXA)、3-甲基胆蒽(3MC)、氯贝特(CLOF)和异烟肼(INH)诱导或诱导的大鼠 MICs。用 3MC 诱导的小鼠和大鼠 MICs 产生 CBZ 细胞毒性代谢物的能力最强。这些发现将有助于优化和规范体外毒性试验,并为药物的临床前研究提供指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
期刊最新文献
Molecular imaging of excitability difference between alkaloids/salts (nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide) In-situ polyherbal gel as biomedicine in the management of Alzheimer's disease: Understanding ameliorative potential in Trimethyltin induced neurodegeneration Evaluation of 4 quantification methods for monitoring 16 antidepressant drugs and their metabolites in human plasma by LC-MS/MS Comparative toxicity assessment of selected nanoparticles using different experimental model organisms Evaluating the proarrhythmic risk of delayed-action compounds in serum free cell culture conditions; serum-starvation accelerates/amplifies the effect of probucol on the KCNQ1 + KCNE1 channel
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1