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Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity

Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this i...

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Autores principales: Quagliariello, Vincenzo, Vecchione, Raffaele, Coppola, Carmela, Di Cicco, Chiara, De Capua, Alberta, Piscopo, Giovanna, Paciello, Rolando, Narciso, Viviana, Formisano, Carmen, Taglialatela-Scafati, Orazio, Iaffaioli, Rosario Vincenzo, Botti, Gerardo, Netti, Paolo Antonio, Maurea, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164259/
https://www.ncbi.nlm.nih.gov/pubmed/30223482
http://dx.doi.org/10.3390/nu10091304
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author Quagliariello, Vincenzo
Vecchione, Raffaele
Coppola, Carmela
Di Cicco, Chiara
De Capua, Alberta
Piscopo, Giovanna
Paciello, Rolando
Narciso, Viviana
Formisano, Carmen
Taglialatela-Scafati, Orazio
Iaffaioli, Rosario Vincenzo
Botti, Gerardo
Netti, Paolo Antonio
Maurea, Nicola
author_facet Quagliariello, Vincenzo
Vecchione, Raffaele
Coppola, Carmela
Di Cicco, Chiara
De Capua, Alberta
Piscopo, Giovanna
Paciello, Rolando
Narciso, Viviana
Formisano, Carmen
Taglialatela-Scafati, Orazio
Iaffaioli, Rosario Vincenzo
Botti, Gerardo
Netti, Paolo Antonio
Maurea, Nicola
author_sort Quagliariello, Vincenzo
collection PubMed
description Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35–40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35–40% and increased IL-10 production by 25–27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.
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spelling pubmed-61642592018-10-10 Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity Quagliariello, Vincenzo Vecchione, Raffaele Coppola, Carmela Di Cicco, Chiara De Capua, Alberta Piscopo, Giovanna Paciello, Rolando Narciso, Viviana Formisano, Carmen Taglialatela-Scafati, Orazio Iaffaioli, Rosario Vincenzo Botti, Gerardo Netti, Paolo Antonio Maurea, Nicola Nutrients Article Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35–40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35–40% and increased IL-10 production by 25–27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models. MDPI 2018-09-14 /pmc/articles/PMC6164259/ /pubmed/30223482 http://dx.doi.org/10.3390/nu10091304 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Quagliariello, Vincenzo
Vecchione, Raffaele
Coppola, Carmela
Di Cicco, Chiara
De Capua, Alberta
Piscopo, Giovanna
Paciello, Rolando
Narciso, Viviana
Formisano, Carmen
Taglialatela-Scafati, Orazio
Iaffaioli, Rosario Vincenzo
Botti, Gerardo
Netti, Paolo Antonio
Maurea, Nicola
Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title_full Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title_fullStr Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title_full_unstemmed Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title_short Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity
title_sort cardioprotective effects of nanoemulsions loaded with anti-inflammatory nutraceuticals against doxorubicin-induced cardiotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164259/
https://www.ncbi.nlm.nih.gov/pubmed/30223482
http://dx.doi.org/10.3390/nu10091304
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