Empagliflozin Significantly Prevents the Doxorubicin-induced Acute Cardiotoxicity via Non-antioxidant Pathways
Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague–Dawley rats were randomized into four groups. The co...
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Published in | Cardiovascular toxicology Vol. 21; no. 9; pp. 747 - 758 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.09.2021
Springer Springer Nature B.V |
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Abstract | Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague–Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED (
P
< 0.01), QTc interval (
P
< 0.001), the ratio of karyolysis and karyorrhexis (
P
< 0.001) and infiltrative cell proliferation (
P
< 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group (
P
< 0.001). In the DOX+EMPA group, LVEDD (
P
< 0.05) and LVESD (
P
< 0.01) values, QTc interval (
P
< 0.001), karyolysis and karyorrhexis ratios (
P
< 0.001) and infiltrative cell proliferation were lower (
P
< 0.01); normal cell morphology and EF were higher compared to the DOX group (
P
< 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity. |
---|---|
AbstractList | Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague-Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED (P < 0.01), QTc interval (P < 0.001), the ratio of karyolysis and karyorrhexis (P < 0.001) and infiltrative cell proliferation (P < 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group (P < 0.001). In the DOX+EMPA group, LVEDD (P < 0.05) and LVESD (P < 0.01) values, QTc interval (P < 0.001), karyolysis and karyorrhexis ratios (P < 0.001) and infiltrative cell proliferation were lower (P < 0.01); normal cell morphology and EF were higher compared to the DOX group (P < 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity. Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague–Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED ( P < 0.01), QTc interval ( P < 0.001), the ratio of karyolysis and karyorrhexis ( P < 0.001) and infiltrative cell proliferation ( P < 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group ( P < 0.001). In the DOX+EMPA group, LVEDD ( P < 0.05) and LVESD ( P < 0.01) values, QTc interval ( P < 0.001), karyolysis and karyorrhexis ratios ( P < 0.001) and infiltrative cell proliferation were lower ( P < 0.01); normal cell morphology and EF were higher compared to the DOX group ( P < 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity. Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague-Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED (P < 0.01), QTc interval (P < 0.001), the ratio of karyolysis and karyorrhexis (P < 0.001) and infiltrative cell proliferation (P < 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group (P < 0.001). In the DOX+EMPA group, LVEDD (P < 0.05) and LVESD (P < 0.01) values, QTc interval (P < 0.001), karyolysis and karyorrhexis ratios (P < 0.001) and infiltrative cell proliferation were lower (P < 0.01); normal cell morphology and EF were higher compared to the DOX group (P < 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity. |
Audience | Academic |
Author | Müftüoğlu, Sevda Erdem, Ayşen Dinçsoy, Adnan Berk Gedikli, Esra Zırh, Selim Barış, Veysel Özgür |
Author_xml | – sequence: 1 givenname: Veysel Özgür orcidid: 0000-0002-3021-8612 surname: Barış fullname: Barış, Veysel Özgür email: veyselozgurbaris@gmail.com organization: Department of Cardiology, Dr. Ersin Arslan Research and Education Hospital, Department of Physiology, Faculty of Medicine, Hacettepe University, School of Medicine – sequence: 2 givenname: Adnan Berk surname: Dinçsoy fullname: Dinçsoy, Adnan Berk organization: Department of Physiology, Faculty of Medicine, Hacettepe University, School of Medicine – sequence: 3 givenname: Esra surname: Gedikli fullname: Gedikli, Esra organization: Department of Physiology, Faculty of Medicine, Hacettepe University, School of Medicine – sequence: 4 givenname: Selim surname: Zırh fullname: Zırh, Selim organization: Department of Histology, Faculty of Medicine, Hacettepe University – sequence: 5 givenname: Sevda surname: Müftüoğlu fullname: Müftüoğlu, Sevda organization: Department of Histology, Faculty of Medicine, Hacettepe University – sequence: 6 givenname: Ayşen surname: Erdem fullname: Erdem, Ayşen organization: Department of Physiology, Faculty of Medicine, Hacettepe University, School of Medicine |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34089496$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1007_s10557_024_07604_x crossref_primary_10_3389_fcvm_2022_863314 crossref_primary_10_1007_s43188_023_00204_1 crossref_primary_10_1007_s40272_023_00585_8 crossref_primary_10_1016_j_jaccao_2024_01_007 crossref_primary_10_1038_s41598_023_48678_1 crossref_primary_10_3389_fcvm_2022_992011 crossref_primary_10_1016_j_biopha_2023_115686 crossref_primary_10_1093_toxres_tfad071 crossref_primary_10_1016_j_vph_2023_107171 crossref_primary_10_1016_j_ijcha_2023_101332 crossref_primary_10_1016_j_cpcardiol_2023_102350 crossref_primary_10_3389_fcvm_2022_847012 crossref_primary_10_3389_fcvm_2024_1369250 crossref_primary_10_1093_toxres_tfad007 crossref_primary_10_3390_antiox13060671 crossref_primary_10_3390_ijms23010441 |
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Keywords | Heart failure Empagliflozin Cardiotoxicity Doxorubicin |
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PublicationTitle | Cardiovascular toxicology |
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20 GL Bakris (9665_CR7) 2014; 37 JR Muindi (9665_CR53) 1984; 172 |
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Snippet | Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective... |
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SubjectTerms | Action Potentials - drug effects Animals Antimitotic agents Antineoplastic agents Antioxidants Benzhydryl Compounds - pharmacology Biomedical and Life Sciences Biomedicine Body weight Cardiology Cardiotoxicity Cell growth Cell morphology Cell proliferation Cell Proliferation - drug effects Cytology Diabetes mellitus Disease Models, Animal Doxorubicin Ethylenediaminetetraacetic acid Glucosides - pharmacology Heart Diseases - chemically induced Heart Diseases - pathology Heart Diseases - physiopathology Heart Diseases - prevention & control Heart Rate - drug effects Male Methylene blue Mitochondria, Heart - drug effects Mitochondria, Heart - metabolism Mitochondria, Heart - ultrastructure Morphology Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - ultrastructure Pharmacology/Toxicology Rats Rats, Sprague-Dawley Sodium-Glucose Transporter 2 Inhibitors - pharmacology Stroke Volume - drug effects Ventricular Function, Left - drug effects |
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Title | Empagliflozin Significantly Prevents the Doxorubicin-induced Acute Cardiotoxicity via Non-antioxidant Pathways |
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