کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8538710 | 1561118 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
LELHCAhpfLCRPCA - PCAgamma-aminobutyric acid - اسید گاما آمینو بوتیریکPrinciple component analysis - تجزیه و تحلیل اجزای اصلhierarchical clustering analysis - تجزیه و تحلیل خوشه ای سلسله مراتبیLocomotion - حرکتBehavior - رفتارNeurotoxicity - سمیت عصبیFlavonoids - فلاونوئیدهاGABA - گاباZebrafish - گورخرماهیGABA receptor - گیرنده GABA
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish](/preview/png/8538710.png)
چکیده انگلیسی
The comparative analysis of complex behavioral phenotypes is valuable as a reductionist tool for both drug discovery and defining chemical bioactivity. Flavonoids are a diverse class of chemicals that elicit robust neuroactive and hormonal actions, though bioactivity information is limited for many, particularly for neurobehavioral endpoints. Here, we used a zebrafish larval chemomotor response (LCR) bioassay to comparatively evaluate a suite of 24 flavonoids, and in addition a panel of 30 model neuroactive compounds representing diverse modes of action (e.g. caffeine, chlorpyrifos, methamphetamine, nicotine, picrotoxin). Naïve larval zebrafish were exposed to concentration ranges of each compound at 120â¯hour post-fertilization (hpf) and locomotor activity measured for 5â¯h. The model neuroactive compounds were largely behaviorally bioactive (20 of 30) with most effects phenotypic of their known modes of action. Flavonoids rapidly and broadly elicited hyperactive locomotor effects (22 of 24). Multidimensional analyses compared responses over time and identified three distinct bioactive groups of flavonoids based on efficacy and potency. Using GABAergics to modulate hyperactive responses, two flavonoids, (S)-equol and kaempferol were tested for GABAA receptor antagonism, as well as a known GABAA receptor antagonist, picrotoxin. Pharmacological intervention with positive allosteric modulators of the GABAA receptor, alfaxalone and chlormethiazole, ameliorated the hyperactive response to picrotoxin, but not for (S)-equol or kaempferol. Taken together, these studies demonstrate that flavonoids are differentially bioactive and that the chemobehavioral effects likely do not involve a GABAA receptor mediated mode of action. Overall, the integrative zebrafish platform provides a useful framework for comparatively evaluating high-content chemobehavioral data for sets of structurally- and mechanistically-related flavonoids and neuroactive compounds.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 344, 1 April 2018, Pages 23-34
Journal: Toxicology and Applied Pharmacology - Volume 344, 1 April 2018, Pages 23-34
نویسندگان
Sean M. Bugel, Robert L. Tanguay,