Abstract 11130: Oral Ingestion of Beetroot Juice Reduces Doxorubicin Cardiotoxicity Via Enhancement of Nitric Oxide, Protein Kinase G and Aldehyde Dehydrogenase 2
Background: Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs for cancer and the cardiotoxicity of DOX remains a major problem. We recently reported protective effects of dietary sodium nitrate against DOX cardiotoxicity. Beetroot juice (BRJ) naturally contains high level of nitrate and is rich in flavonoids and vitamins that are known to be antioxidants. We hypothesized that oral ingestion of BRJ may reduce DOX cardiotoxicity via mechanisms involving nitric oxide (NO) dependent signaling and expression of aldehyde dehydrogenase 2 (ALDH2) - a cardioprotective protein for detoxification of aldehydes.
Methods & Results: Adult male CF-1 mice were divided into 4 groups: 1) Saline [0.2 ml, IP]; 2) DOX [single IP injection of 15 mg/kg DOX]; 3) BRJ - BRJ extract was added into the animals’ drinking water (10 g/L) for 13 days; 4) BRJ+DOX - mice ingested BRJ 7 days before the DOX injection and continued for the 5-day post-DOX period. Five days after DOX injection, the mice were sacrificed for collection of blood and ventricular tissue samples. As shown in Fig. A, serum levels of cardiac troponin I (cTnI) was significantly elevated in DOX-treated mice as compared with the controls. BRJ intake completely prevented the cTnI release caused by DOX cardiotoxicity. The cardioprotection by BRJ was associated with enhanced NO production as indicated by plasma nitrate+nitrite (NOx, Fig. B) and increased activity of cGMP-dependent protein kinase (PKG) in heart (Fig. C). The Western blot analysis (Fig. D) also revealed complete normalization of cardiac expression of ALDH2, which was inhibited by DOX.
Conclusion: We have showed for the first time that oral ingestion of BRJ reduces DOX cardiotoxicity. The BRJ-induced cardioprotection is likely mediated by the enhanced NO-PKG signaling pathway and restoration of ALDH2. Since BRJ is a natural and safe food product, it can be used as a cardioprotectant in combating DOX cardiotoxicity, along with its reported anti-cancer properties.
- © 2012 by American Heart Association, Inc.