Influence of omega 3 in doxorubicin-induced cardiotoxicity in rats: role of ceramide pathway

Abstract

Cardiotoxicity is the major side effect of doxorubicin treatment. The identification of mechanisms involved in pathophysiology of cardiotoxicity allows the discovery news strategies to attenuate this complication. Ceramide is formed by the metabolism of membrane cell phospholipids and participates in intracellular signaling and modulates pathological pathways. Supplementation of omega 3 could act in cell membranes and could interfere in ceramide pathway. Aim: to evaluate the role of ceramide pathway in pathophysiology of doxorubicin-induced cardiotoxicity in rats and the influence of omega 3 supplementation on the attenuation of myocardial damage in this model. Material and Methods: male Wistar rats (n = 60) will be used, which will be allocated in 4 groups: control, omega 3 supplementation, doxorubicin and doxorubicin plus omega 3 supplementation. Omega 3 (400mg/kg/day) will be supplied via gavage for 6 weeks. After 2 weeks, doxorubicin administration will be started (3,5mg/kg, ip, 1x/week) for 4 weeks. Echocardiogram will be performed to evaluate cardiac function. The hearts will be collected to perform oxidative stress analysis, mitochondrial metabolism, sphingomyelinase activity and western blot to determine ceramide, caspase-3, TNF-±, NF-kB and Ik-B expression. Statistical analysis will be performed by two-way ANOVA and will be adopted significance level of 5% for all analysis. (AU)