Dimethyl fumarate interferes with MyD88-dependent toll-like receptor signalling pathway in isoproterenol-induced cardiac hypertrophy model

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 ISO-induced cardiac hypertrophy. This effect is suggested to be through interfering with TLR signalling pathway.

Keywords: MyD88; TLR signalling pathway; cardiac hypertrophy; dimethyl fumarate; isoproterenol.