کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5846674 1128495 2013 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury
ترجمه فارسی عنوان
تست نفوذ سنجی با کارایی بالا، سمیت فاکتور پیش بینی آسیب های میتوکندری را مشخص می کند
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- Respirometric assay conducted in RPTC to create mitochondrial toxicant database.
- Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores
- Mitochondrial toxicophore identifies five novel mitochondrial toxicants.

Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 272, Issue 2, 15 October 2013, Pages 490-502
نویسندگان
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