Abstract 10893: Dietary Nitrate Supplementation With Beetroot Juice Enhances Cardiac Autophagy Markers AMBRA-1 (Activating Molecule in Beclin-1-regulated Autophagy) and ATG-5 (Autophagy-related Gene 5): Protective Role Against Doxorubicin Cardiotoxicity

• DOI: 10.1161/circ.132.suppl_3.10893
• Publication Date: 2024-04-23T10:56:22Z
• Authors: Chang Yin; Shabina Rehman; Rakesh C Kukreja; Lei Xi

Background: Beetroot juice (BRJ) is a dietary supplement containing high levels of nitrate and other nutrients. We previously reported that oral intake BRJ protects against cardiotoxicity doxorubicin (DOX) - widely used anticancer drug. diminished cell injury (indicated by significantly lower serum cardiac troponin I) ventricular dysfunction caused DOX. However, it remains unknown if modulates autophagy critical endogenous cellular quality control damaged organelles removal mechanism, particularly under DOX-induced cardiototoxic stress. Therefore, the current study designed to determine cardioprotective dose affects autophagy. Methods: Adult male CF-1 mice were divided into 4 groups (n=3-4/group) receive: 1) Saline (0.2 ml, IP); 2) DOX (15 mg/kg, 3) (10 g extract per liter drinking water provided for 13 days); 4) BRJ+DOX (BRJ 7 days before injection on Day 8 throughout 5-day post-DOX period. On 13, heart tissue samples collected determining key markers with real-time PCR or Western blots. Results: Cardiac protein expression AMBRA-1 (Fig. A) ATG-5 C) was enhanced without co-treatment (P<0.05). Interestingly, also augmented mRNA B) D) in group. Furthermore, ratio LC3B-II/LC3B-I, another hallmark decreased group, but restored group level Conclusions: upregulates several molecular such as ATG-5, which may contribute BRJ-induced protection cardiotoxicity. The autophagy-related novel mechanisms revealed this provide new rationale potential use safe nutraceutical therapy reducing chemotherapy.