Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway
| Autor: | Nawal M. Al-Rasheed, Nouf M. Al-Rasheed, Reem Z Al-Manee, Maha M Al-Oteibi, Raeesa A. Mohamad, Sarah A Al-Shareef, Ayman M. Mahmoud, Iman H. Hasan |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
STAT3 Transcription Factor Simvastatin medicine.medical_specialty Pharmaceutical Science Cardiomegaly Creatine chemistry.chemical_compound Fibrosis Internal medicine Drug Discovery Troponin I JAK/STAT pathway medicine Animals Creatine Kinase MB Form Myocytes Cardiac Phosphorylation Rats Wistar Original Research Janus Kinases Pharmacology IL-6 Drug Design Development and Therapy isoproterenol Interleukin-6 business.industry cardiac hypertrophy NF-kappa B medicine.disease Lipids Disease Models Animal Endocrinology medicine.anatomical_structure Blood pressure chemistry Cytoprotection Ventricle STAT protein Hydroxymethylglutaryl-CoA Reductase Inhibitors Janus kinase business Biomarkers Signal Transduction medicine.drug |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Nouf M Al-Rasheed,1 Maha M Al-Oteibi,1 Reem Z Al-Manee,1 Sarah A Al-Shareef,1 Nawal M Al-Rasheed,1 Iman H Hasan,1 Raeesa A Mohamad,2 Ayman M Mahmoud3 1Department of Pharmacology, Faculty of Pharmacy, 2Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Physiology Division, Department ofZoology, Faculty of Science, Beni-Suef University, Egypt Abstract: Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180–200g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10mg/kg body weight) for 30days per gavage. In the last 7days, rats of groups III and IV were administered ISO (5mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals. Keywords: simvastatin, cardiac hypertrophy, JAK/STAT pathway, IL-6, isoproterenol |
| Databáze: | OpenAIRE |
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