Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response
Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the phar...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0d3516619e54407092e9017002a7de8a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0d3516619e54407092e9017002a7de8a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0d3516619e54407092e9017002a7de8a2021-11-25T18:36:33ZIcariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response10.3390/nu131140702072-6643https://doaj.org/article/0d3516619e54407092e9017002a7de8a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4070https://doaj.org/toc/2072-6643Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived <i>embryonic cardiac</i> myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 μM and 5 μM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival.Miriam ScicchitanoCristina CarresiSaverio NuceraStefano RugaJessica MaiuoloRoberta MacrìFederica ScaranoFrancesca BoscoRocco MollaceAntonio CardamoneAnna Rita CoppolettaLorenza GuarnieriMaria Caterina ZitoIrene BavaLuca CariatiMarta GrecoDaniela Patrizia FotiErnesto PalmaMicaela GliozziVincenzo MusolinoVincenzo MollaceMDPI AGarticlecardiomyoblastsDoxorubicinIcariinoxidative stressautophagyNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4070, p 4070 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
cardiomyoblasts Doxorubicin Icariin oxidative stress autophagy Nutrition. Foods and food supply TX341-641 |
| spellingShingle |
cardiomyoblasts Doxorubicin Icariin oxidative stress autophagy Nutrition. Foods and food supply TX341-641 Miriam Scicchitano Cristina Carresi Saverio Nucera Stefano Ruga Jessica Maiuolo Roberta Macrì Federica Scarano Francesca Bosco Rocco Mollace Antonio Cardamone Anna Rita Coppoletta Lorenza Guarnieri Maria Caterina Zito Irene Bava Luca Cariati Marta Greco Daniela Patrizia Foti Ernesto Palma Micaela Gliozzi Vincenzo Musolino Vincenzo Mollace Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| description |
Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived <i>embryonic cardiac</i> myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 μM and 5 μM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival. |
| format |
article |
| author |
Miriam Scicchitano Cristina Carresi Saverio Nucera Stefano Ruga Jessica Maiuolo Roberta Macrì Federica Scarano Francesca Bosco Rocco Mollace Antonio Cardamone Anna Rita Coppoletta Lorenza Guarnieri Maria Caterina Zito Irene Bava Luca Cariati Marta Greco Daniela Patrizia Foti Ernesto Palma Micaela Gliozzi Vincenzo Musolino Vincenzo Mollace |
| author_facet |
Miriam Scicchitano Cristina Carresi Saverio Nucera Stefano Ruga Jessica Maiuolo Roberta Macrì Federica Scarano Francesca Bosco Rocco Mollace Antonio Cardamone Anna Rita Coppoletta Lorenza Guarnieri Maria Caterina Zito Irene Bava Luca Cariati Marta Greco Daniela Patrizia Foti Ernesto Palma Micaela Gliozzi Vincenzo Musolino Vincenzo Mollace |
| author_sort |
Miriam Scicchitano |
| title |
Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| title_short |
Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| title_full |
Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| title_fullStr |
Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| title_full_unstemmed |
Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response |
| title_sort |
icariin protects h9c2 rat cardiomyoblasts from doxorubicin-induced cardiotoxicity: role of caveolin-1 upregulation and enhanced autophagic response |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/0d3516619e54407092e9017002a7de8a |
| work_keys_str_mv |
AT miriamscicchitano icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT cristinacarresi icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT saverionucera icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT stefanoruga icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT jessicamaiuolo icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT robertamacri icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT federicascarano icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT francescabosco icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT roccomollace icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT antoniocardamone icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT annaritacoppoletta icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT lorenzaguarnieri icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT mariacaterinazito icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT irenebava icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT lucacariati icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT martagreco icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT danielapatriziafoti icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT ernestopalma icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT micaelagliozzi icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT vincenzomusolino icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse AT vincenzomollace icariinprotectsh9c2ratcardiomyoblastsfromdoxorubicininducedcardiotoxicityroleofcaveolin1upregulationandenhancedautophagicresponse |
| _version_ |
1718410875822407680 |