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Pachymic acid attenuated doxorubicin-induced heart failure by suppressing miR-24 and preserving cardiac junctophilin-2 in rats.
Faculty
Medicine
Year:
2021
Type of Publication:
ZU Hosted
Pages:
Authors:
Mohammed Abdul Rahman Ghoneim Shahin
Staff Zu Site
Abstract In Staff Site
Journal:
International Journal of Molecular Sciences MDPI
Volume:
Keywords :
Pachymic acid attenuated doxorubicin-induced heart failure
Abstract:
Defects in cardiac contractility and heart failure (HF) are common following doxorubicin (DOX) administration. Different miRs play role in HF and their targeting was suggested as a promising therapy. We aimed to target miR-24, a suppressor upstream of junctophilin-2 (JP-2), which is required to affix sarcoplasmic-reticulum to T-tubules and hence the release of Ca2+ in excitation-contraction coupling using pachymic acid (PA) and/or losartan (LN). HF was induced with DOX (3.5mg/kg, i.p six-doses, twice weekly) in 24 rats. PA and LN (10mg/kg, daily) were given orally for four-weeks starting the next day of last DOX dose. Echocardiography, left ventricle (LV) biochemical and histological assessment and electron-microscopy were conducted. DOX increased serum BNP, HW/TL, HW/BW, mitochondrial number/size and LV expression of miR-24, while decreased EF, cardiomyocyte fiber diameter, LV content of JP-2 and rayanodine receptors-2 (RyR2). Treatment with either PA or LN reversed these changes. Combined PA+LN attained better results than monotherapies. In conclusion, HF progression following DOX administration can be prevented or even delayed by targeting miR-24 and its downstream JP-2. Our results therefore suggested a possibility of using PA alone or as an adjuvant therapy with LN to attain better management of HF patients specially those develop tolerance towards LN.
Author Related Publications
Mohammed Abdul Rahman Ghoneim Shahin, "A Comparative Study of the Ameliorative Effect of Doxorubicin with Vitamin E versus Liposomal Doxorubicin on the Left Ventricular Histological and Immunohisochemical Changes Induced by Doxorubicin in Adult Male Albino Rats", Lippincott Williams and Wilkins Ltd, 2019
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Mohammed Abdul Rahman Ghoneim Shahin, "Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury", USA, 2011
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Mohammed Abdul Rahman Ghoneim Shahin, "Plasma Membrane Calcium Pump (PMCA4)-Neuronal Nitric-oxide Synthase Complex Regulates Cardiac Contractility through Modulation of a Compartmentalized Cyclic Nucleotide Microdomain", Elsevier, 2011
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Mohammed Abdul Rahman Ghoneim Shahin, "The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line", Elsevier, 2016
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Department Related Publications
Ahmed Shafea Mahmoud Morsy, "تاثير توسيع الصمام الميترالي بالقسطرة البالةنية على ارتجاع الوظيفي للصمام ثلاثى الشرفات وارتفاع ضغط الشريان الرئوى", مجلة جامعة الزقازيق الطبية, 2000
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Mohamed Ibrahim Mustafa AlAwadi, "القيمة التنبؤية لقصور الشريان التاجى الخفى فى مرضى احتشاء عضلة القلب الحاد اثناء فترة الاقامة بالمستشفى", مجلة جامعة الزقازيق الطبية, 2000
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