الفهرس | Only 14 pages are availabe for public view |
Abstract Abstract Objectives: To investigate the effect of dimethyl fumarate (DMF) on Toll-like receptor (TLR) signalling pathway in isoproterenol (ISO)-induced cardiac hypertrophy in rats. Methods: Sixty adult male Sprague-Dawley rats were randomly allocated into three groups, group I: rats received the vehicles only; group II: rats were treated with ISO (5 mg/kg per day S.C.) to induce cardiac hypertrophy for 7 days; and group III: rats were given DMF (25 mg/kg per 12 h P.O.) for 28 days, and at the last 7 days, they were treated with ISO (5 mg/kg per day S.C.). Key findings: Pretreatment with DMF decreased heart-to-body weight ratio, heart rate and blood pressure and improved the electrocardiographic patterns when compared with ISO group. DMF exhibited cardioprotective effect as evidenced by the reduction in cardiac troponin I, creatine kinase-MB and atrial natriuretic peptide levels. Moreover, DMF alleviated the changed oxidative stress and inflammatory biochemical markers through its anti-inflammatory and antioxidant effects. DMF interfered with TLR signalling pathway, evidenced by decreased levels of the TLR adaptor protein MyD88 and p-ERK1/2 and increased p-Akt level. Conclusions: Dimethyl fumarate exerted cardioprotective effect against ISOinduced cardiac hypertrophy. This effect is suggested to be through interfering with TLR signalling pathway. from the obtained results, it can be concluded that: 1- Injection of Isoproterenol to the rats caused the development of cardiac hypertrophy through chronic β-AR activation which causes hemodynamic alterations, changes in cardiac functions, and increase in the size of the cardiac muscle. In addition, it stimulates different pathological pathways such as oxidative stress, inflammation and MyD88-dependent TLR activation. These pathways are involved in the hypertrophic process of the heart. 2- Treatment of rats with dimethyl fumarate for 28 days showed a protective effect against isoproterenol-induced cardiac hypertrophy through its antioxidant and anti-inflammatory effects. This caused an improvement in the hemodynamic measurements and the cardiac functions. 3- Treatment of rats with dimethyl fumarate for 28 days interfered with the inflammatory pathways of MyD88-dependent TLR signaling pathway and supported the effect of the anti-inflammatory pathway of the receptor allowing to counteract the inflammatory response induced by the receptor activation. from the current study, it is greatly recommended that DMF has a beneficial effect in management of cardiac hypertrophy and delaying the progression of the disease in rats. However, further clinical trials are warranted to prove this suggestion. |