Abstract 3293
Background
Empagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2, reduces the risk of hospitalization for heart failure or cardiovascular death, as seen in the EMPA-REG OUTCOME trial.
Methods
We incubated EMPA alone or in combination with Doxorubicin in HL-1 adult cardiomyocytes evaluating: cell viability, lipid peroxidation, Leukotriene-B4 expression, NF-κB activation and Interleukin 1β, 8 and 6 secretion. To evaluate cardiac function in vivo, Global Longitudinal Strain (GLS) was measured using 2D speckle tracking echocardiography in C57BL6 mice treated with Doxorubicin (2.25 mg/kg/day ip) or EMPA (10 mg/kg/day) or EMPA and Doxorubicin in combination for 7 days. Cardiac lysates were processed for analysis of pro-inflammatory Interleukins.
Results
EMPA, co-incubated with Doxorubicin, enhanced significantly the viability of cardiomyocytes, compared to only Doxorubicin treated cells. EMPA reduces the lipid peroxidation during exposure to Doxorubicin. Moreover, EMPA has shown anti-inflammatory activity reducing both Leukotriene B4 and NF-kB expression. Notably, EMPA also decreased the expression of IL-1β, IL-6 and IL-8 of 40-50 % for all, compared to only Doxorubicin exposed cells. In preclinical models, after treatments only with Doxorubicin, GLS decreased significantly, while associating the pretreatment and subsequent combinatorial treatment with EMPA, we observed a prevention of the GLS’s reduction, indicating cardiprotective effects of the hypoglycemic drug. Moreover, we demonstrated that mice treated with EMPA and Doxorubicin the cardiac IL-1β, IL-6 and IL-8 were reduced of 45-60 % compared to mice treated only with Doxorubicin.
Conclusions
We demonstrated for the first time that EMPA exerts anti-oxidant and anti-inflammatory properties during incubation with Doxorubicin. Preclinical studies demonstrated cardioprotective effects of EMPA, with significant reductions of key mediators of cardiotoxicity. These results lay the biochemical and pathophysiological bases for subsequent preclinical and clinical studies concerning the use of EMPA as a cardioprotective agent during treatment with Doxorubicin.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
“Ricerca Corrente” grant from the Italian Ministry of Health.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3524 - Cabazitaxel For Octogenarian Patients With Metastatic Castration-Resistant Prostate Cancer (MCRPC).
Presenter: Paolo Tralongo
Session: Poster Display session 3
Resources:
Abstract
5637 - External Validation of a Prognostic Score in First-Line Metastastic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: David Lorente
Session: Poster Display session 3
Resources:
Abstract
3228 - Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPRI-registry
Presenter: Jessica Notohardjo
Session: Poster Display session 3
Resources:
Abstract
4695 - Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion>5%: a propensity score matching analysis from SEER database
Presenter: Junru Chen
Session: Poster Display session 3
Resources:
Abstract
4438 - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT
Presenter: Morgane Guibert-broudic
Session: Poster Display session 3
Resources:
Abstract
4574 - Safety of new androgen receptor inhibitors (ARi) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a network meta-analysis of randomized controlled trials (RCT)
Presenter: Amelia Altavilla
Session: Poster Display session 3
Resources:
Abstract
3816 - Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry
Presenter: Malou Kuppen
Session: Poster Display session 3
Resources:
Abstract
5180 - A phase 2a study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
1067 - Adding ADT to PSMA-PET/CT-guided SBRT for oligometastatic prostate cancer improves distant progression-free survival
Presenter: Carole Mercier
Session: Poster Display session 3
Resources:
Abstract
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract