کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5846321 | 1128475 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice
ترجمه فارسی عنوان
در معرض قرار گرفتن در معرض دوزهای پایین داروها، بیان کبدی ژنهای روزانه در موشهای نابالغ و چاق اختلال ایجاد میکند
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کلمات کلیدی
ARNTLCytochromes P450APAPGSEAbrain and muscle ARNT-like 1ALTCRY1RT-qPCRcryptochrome 1GEOALAS1ATP2B2DBPNpas2neuronal PAS domain protein 2Bmal1 - BMAL1CYPs - CYPH&E - H & EAST - آسپارتات ترانس آمینازAspartate aminotransferase - آسپارتات ترانس آمیناز یا AST Alanine aminotransferase - آلانین آمینوترانسفرازAcetaminophen - استامینوفن Gene Set Enrichment Analysis - تجزیه و تحلیل غنی سازی مجموعه ژنیDrug - داروper - در هرCircadian rhythm - ریتم شبانه روزیMicroarray - ریزآرایهreal-time quantitative PCR - زمان واقعی PCR کمیClock - ساعتMetallothionein - متالوتونیئینObesity - مرض چاقیMouse - موشhematoxylin-eosin - هماتوکسیلین ائوزینcircadian locomotor output cycles kaput - چرخه خروجی موتور حرکتی روزمره استGene Expression Omnibus - ژن بیان OmnibusLiver - کبد
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4Â months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 106Â ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 106Â ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 102-103Â ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 276, Issue 1, 1 April 2014, Pages 63-72
Journal: Toxicology and Applied Pharmacology - Volume 276, Issue 1, 1 April 2014, Pages 63-72
نویسندگان
Sébastien Anthérieu, Dounia Le Guillou, Cédric Coulouarn, Karima Begriche, Viviane Trak-Smayra, Sophie Martinais, Mathieu Porceddu, Marie-Anne Robin, Bernard Fromenty,