Abstract
Doxorubicin (Dox) is an indispensable chemotherapeutic agent associated with damaging cardiotoxicity. Baicalin (BA) is a flavonoid, extracted from the medicinal plant, Scutellariae baicalensis Georgi. BA is well-known for its anti-inflammatory and antioxidant effects. Our study investigated the potential effect of BA in attenuating Dox-induced cardiotoxicity. To this end, male Swiss albino mice were given BA (100 mg/kg/day, orally) for four weeks and were challenged with Dox (six i.p. doses, each 2.5 mg/kg, every other day with a final cumulative dose of 15 mg/kg). Serum activities of cardiac biomarkers; cTn-I, CK-MB, LDH, and AST were assessed along with the histopathological examination of the heart tissues. Gene expression of Toll-like receptor 4 (TLR4) was analyzed by qRT-PCR. Analysis of the protein levels of β-catenin and NF-κB was done immunohistochemically. Cardiac Dickkopf-1 (DKK1) and IL-1β were quantified by ELISA. Cardiac levels of reduced glutathione (GSH) and malondialdehyde (MDA) were detected spectrophotometrically. Pretreatment with BA significantly prevented Dox-induced elevation of serum activities of cardiac biomarkers and alterations to the heart. Moreover, BA suppressed the gene overexpression of cardiac TLR4 and subsequently, prevented Dox-induced elevation of both cardiac NF-κB and IL-1β. BA, also, significantly reduced the cardiac levels of DKK1 and elevated the level of β-catenin. Dox-induced elevation of MDA and reduction of GSH were reversed by BA. BA exhibited a novel cardioprotective effect against Dox-induced cardiotoxicity. The cardioprotective effect was indicated through the inhibition of the inflammatory TLR4/NF-κB pathway and the activation of the protective Wnt/β-catenin pathway by the suppression of DKK1.
