الفهرس | Only 14 pages are availabe for public view |
Abstract Doxorubicin (Dox) is an important chemotherapeutic agent, but unfortunately, is associated with serious cardiotoxicity. Baicalin (BAI) and catechin (CAT) are effective natural compounds. BAI and CAT are well-known for their anti-inflammatory and antioxidant effects. This study aimed to investigate the protective effects of BAI, CAT and their combination in attenuating Dox-induced cardiotoxicity. Methods : male Swiss albino mice were divided into five groups; control, Dox (2.5 mg/kg/every other day, i.p., 6 doses for 2 weeks), BAI (100 mg/kg/day, orally), CAT (100 mg/kg/day, orally), and BAI+CAT. Both BAI and CAT were administered two weeks previous to Dox and continued during Dox treatment. Key findings : Pretreatment with BAI and/or CAT significantly prevented Dox-induced elevation of serum activities of cardiac biomarkers and alterations to the heart. Moreover, BAI and/or CAT suppressed the gene overexpression of cardiac TLR4 and subsequently, prevented Dox-induced elevation of both cardiac NF-κB and IL-1β. BAI and/or CAT, 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 BAI and/or CAT. Significance: BAI and CAT exhibited a significant cardioprotective effect against Dox-induced cardiotoxicity 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. |