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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.