کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8539201 | 1561152 | 2016 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F1 mice
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کلمات کلیدی
MCHimmunoglobin GMCHCMCVDSBDABcTNTDOXRBCIgGHCTWBCMCsRed blood cells - سلولهای قرمز خونROS - ROSDNA damage - آسیبDNAcardiac troponin T - تروپونین T قلبSex-based differences - تفاوت های جنسیتیTUNEL - تونلMean corpuscular volume - حجم متوسط مایعApoptosis - خزان یاختهایRoom temperature - دمای اتاقDNA double strand breaks - دو رشته DNA شکسته می شودDoxorubicin - دوکسوروبیسینdoxorubicinol - دوکسوروبیکینولdiaminobenzidine - دیامینو بنزیدینCardiotoxicity - سمیت قلبیMast cells - ماست سل هاmean corpuscular hemoglobin - متوسط هموگلوبین عضلانیMouse model - مدل موشMean corpuscular hemoglobin concentration - میانگین غلظت هموگلوبین عروق کرونرhematocrit - هماتوکریتHemoglobin - هموگلوبینHgb - هورمون رشدwhite blood cells - گلبول های سفید خونReactive oxidative species - گونه های واکنش پذیر اکسیداتیو
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F1 mice were dosed with 3 mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27 mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24 mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21 mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27 mg/kg cumulative dose and right atrium at 21 and 27 mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 310, 1 November 2016, Pages 159-174
Journal: Toxicology and Applied Pharmacology - Volume 310, 1 November 2016, Pages 159-174
نویسندگان
G. Ronald Jenkins, Taewon Lee, Carrie L. Moland, Vikrant Vijay, Eugene H. Herman, Sherry M. Lewis, Kelly J. Davis, Levan Muskhelishvili, Susan Kerr, James C. Fuscoe, Varsha G. Desai,