Cardioprotective effect of vanillic acid against doxorubicin-induced cardiotoxicity in rat.

Doxorubicin (DOX) is an effective agent for the treatment of many neoplastic diseases. Cardiotoxicity is the major side effect of this drug and limits its use. Vanillic acid (VA) is a pharmaceutical compound from the phenolic acids family. The present study is an attempt to investigate the possible helpful effects of VA against DOX-induced cardiotoxicity in rats.For induction of cardiotoxicity, male Wistar rats received total of six doses of DOX (2.5 mg/kg i.p.) three times per week from days 14 to 28. Treatment groups received daily oral doses of VA (10, 20, and 40 mg/kg) two weeks before DOX injection and then plus DOX for 2 weeks. At the end of experiment, systolic blood pressure (SBP) and heart rate (HR) were detected using tail-cuff method. Lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), serum glutamic oxaloacetic transaminase (SGOT), malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP) were measured in serum samples. Troponin-I and toll-like receptor 4 (TLR4) were measured in cardiac tissue. All the measurements processed spectrophotometrically using commercial ELISA kits. Cardiac tissue was also processed for histopathological examination.Treatment with VA significantly increased SBP compared to the DOX group and restored HR near to the normal level. Administration of VA at all of doses, decreased serum levels of LDH, SGOT, CK-MB, MDA, cardiac troponin-I, cardiac TLR4 and increased FRAP value.These results suggest that VA may exert cardioprotective effects against DOX-induced cardiotoxicity by decreasing oxidative stress and biomarkers of cardiotoxicity, suppression of TLR4 signaling and consequently inflammation pathway.