Myocardial hypertrophy is prevented by farnesol through oxidative stress and ERK1/2 signaling pathways
| Autor: | Diego Santos de Souza, Jader S. Cruz, Carla Maria Lins de Vasconcelos, Michael Nadson Santos Santana, Adriana Gibara Guimarães, Michael Ramon de Lima Conceição, Lucindo José Quintans-Júnior, Thallita Kelly Rabelo, Tatiane de Oliveira Barreto, Aimée Obolari Durço, José Evaldo Rodrigues de Menezes-Filho, Luana Heimfarth, Paula Rhana |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine MAP Kinase Signaling System Blood Pressure Cardiomegaly Caspase 3 Pharmacology medicine.disease_cause Antioxidants Ventricular Function Left Electrocardiography 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis medicine Animals Rats Wistar Protein kinase B Cardioprotection chemistry.chemical_classification Reactive oxygen species biology Isoproterenol Farnesol Adrenergic beta-Agonists medicine.disease Rats Oxidative Stress 030104 developmental biology chemistry Catalase cardiovascular system biology.protein lipids (amino acids peptides and proteins) Lipid Peroxidation Apoptosis Regulatory Proteins Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | European Journal of Pharmacology. 887:173583 |
| ISSN: | 0014-2999 |
| Popis: | Farnesol is a sesquiterpene found in several plants, with multiple pharmacological activities. However, pharmacological actions of farnesol in the treatment of cardiac hypertrophy are not yet reported. This study aimed to investigate the effect and regulatory mechanisms of farnesol against isoproterenol-induced pathological cardiac hypertrophy. Male Wistar rats were treated for 8 days with isoproterenol (4.5 mg/kg; i. p.) and with farnesol (50 μM; i. p.). Hearts were subjected to evaluation of left ventricular developed pressure (LVDP), coronary pressure, electrocardiogram, histopathological analysis, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and pro- and anti-apoptosis protein expression. The results showed that severe impairment of LVDP induced by cardiac hypertrophy was significantly prevented by farnesol treatment. Moreover, farnesol attenuated electrocardiographic changes that are characteristic of cardiac hypertrophy, as well as prevented the increase of fibrosis and migration of inflammatory cells in cardiac tissue. Additionally, farnesol treatment prevented the increase of cardiac ROS generation and restored the activity of endogenous antioxidant enzymes, such as SOD and catalase. It was also evidenced that farnesol decreased the ERK1/2, Bax and Caspase 3 activation, and an increase of AKT and Bcl-2 protein expression, which can be associated with the pathological cardiac remodeling and also with cardioprotection mediated by farnesol, respectively. These results suggest that farnesol is a novel therapeutic agent for amelioration of cardiac hypertrophy in rats. |
| Databáze: | OpenAIRE |
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