Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Empaglifozin has cardioprotective and anti-inflammatory effects during doxorubicin treatment: A preclinical study.
Symptoms and Survivorship
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e23057)
Author(s): Nicola Maurea, Vincenzo Quagliariello, Carmela Coppola, Domenica Rea, Antonio Barbieri, Claudio Arra, Gerardo Botti; Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”-IRCCS, Naples, Division of Cardiology, Naples, Italy; Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy; Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”-IRCCS, Naples, Animal Facility, Naples, Italy; National Cancer Institute, Pascale Foundation, Naples, Italy; Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale, IRCCS, Naples, Animal Facility, Naples, Italy; Istituto Nazionale Tumori Fondazione G.Pascale, Naples, Italy
Background: Empagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2 (SGLT2), reduces the risk of hospitalization for heart failure or cardiovascular death in type 2 diabetic patients. We aimed to study if EMPA could have cardioprotective and anti-inflammatory effects in Doxorubicin (DOXO) - Induced cardiotoxicity. Methods: we tested the effects of EMPA alone or in combination with DOXO in HL-1 adult cardiomyocytes evaluating: mitochondrial viability, lipid peroxidation, Leukotriene-B4 expression, p65-NF-κB activation and Interleukin 1β, 8 and 6 secretion. To evaluate cardiac function, Global Longitudinal Strain (GLS) were measured using 2D speckle tracking echocardiography in C57BL6 mice pretreated with EMPA (10 mg/kg/day) per os for 3 days. EMPA was then administered for additional 7 days, alone and in combination with DOXO (2.25 mg/kg/day ip). Cardiac lysates were processed for analysis of pro-inflammatory Interleukins. Results: EMPA, co-incubated with DOXO, is able to increase the cardiomyocyte viability of 33,6 and 82,3 % at 100 and 500 nM, respectively (compared to only DOXO treated cells). EMPA inhibits the lipid peroxidation by decreasing MDA and 4-HNA production of around 23,6 and 28,7 %, at 100 nM and of 47,8 and 52,1 % at 500 nM, respectively, compared to untreated cells. Moreover, EMPA has anti-inflammatory activity with a reduction of Leukotriene B4 expression and p65-NFkb activation of 58,4 and 64,3 % at 500 nM, respectively (compared to only DOXO treated cells). EMPA also decreased the expression of Interleukin 1β (of 28,5 and 68,8 %), Interleukin-8 (of 21,2 and 57,3 % ) and Interleukin-6 (of 28,1 and 49,8 %) at 100 and 500 nM, respectively, compared to only DOXO exposed cells. Preclinically, after 7 days with DOXO, GLS decreased. Interestingly, in mice treated with EMPA+DOXO, EMPA prevents the GLS’s reduction : GLS was 19.24 ± 1.5 (p < 0,01) vs DOXO alone. In DOXO-EMPA groups, the heart IL-1β, IL-6 and IL-8 tissue extract were reduced of 48, 54,4 and 58,2 % compared to only DOXO groups. Conclusions: EMPA has strong anti-inflammatory and cardioprotective effects in DOXO-Induced cardiotoxicity and these effects are mainly mediated by a reduction of the lipid peroxidation, Leukotriene-B4 and NF-κB activation.