Protective Effect of Omega-3 and the Potential of Toll-like Receptor Gene Expression in Rats with Doxorubicin-induced Cardiac Toxicity

Abstract

Despite the clinical signs of doxorubicin (DOX)-induced cardiomyopathy, the mechanisms underlying DOX-induced cardiac damage are unknown. Toll-like receptors (TLRs) allow cardiomyocytes to respond to either endogenous or external signals, both of which have the potential to alter the pathophysiological responses to dilated cardiomyopathy. Omega-3 (OMG-3) precursors are highly active metabolites with numerous therapeutic benefits in the prevention and/or treatment of a variety of diseases. Thus, this study was aimed at evaluating the preventive effect of omega-3 on rats suffering from acute DOX-induced cardiotoxicity associated with TLR gene expression. Thirty rats were divided into five equal groups; Group 1 received no treatment, Group 2 received doxorubicin (at a toxic dose of 20 mg/kg), and Groups 3-5 received doxorubicin (20 mg/kg) after receiving OMG-3 at various doses (100, 200, and 400 mg/kg/day, respectively) for 4 weeks. At the end of the experiment, blood samples were obtained from the heart. The real time polymerase chain reaction (RT-PCR) was used to assess TLR2 and TLR4 gene expression. TLR2 had a significantly (p<0.01) elevated fold change in the DOX alone group (28.74+4.95), whereas TLR2 expression was significantly reduced in the OMG-3 pretreated groups (1.633+0.51, 0.733+0.13, and 0.709+0.16, respectively). TLR4 fold change in the DOX alone group was 8.57+1.22, whereas TLR4 expression was significantly reduced in the OMG-3 pretreated groups (100, 200, and 400 mg/kg) with values of 0.809+0.32, 0.852+0.50, and 0.272+0.16, respectively. The findings of this study revealed that OMG-3 decreased doxorubicin-induced cardiotoxicity and showed a significant cardioprotective effect by lowering TLR2 and TLR4 gene expression.