Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity.
Journal
Anatolian journal of cardiology
ISSN: 2149-2271
Titre abrégé: Anatol J Cardiol
Pays: Turkey
ID NLM: 101652981
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
medline:
2
6
2023
pubmed:
31
5
2023
entrez:
31
5
2023
Statut:
ppublish
Résumé
Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity. A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity. Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group. Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.
Sections du résumé
BACKGROUND
Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity.
METHODS
A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity.
RESULTS
Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group.
CONCLUSION
Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.
Identifiants
pubmed: 37257007
doi: 10.14744/AnatolJCardiol.2023.2825
pmc: PMC10250773
doi:
Substances chimiques
dapagliflozin
1ULL0QJ8UC
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
339-347Références
Agents Actions. 1989 Mar;26(3-4):378-85
pubmed: 2544086
BMC Med. 2022 Sep 7;20(1):309
pubmed: 36068525
Pharmacol Res. 2001 Mar;43(3):211-8
pubmed: 11401411
Eur Rev Med Pharmacol Sci. 2022 Jun;26(12):4403-4408
pubmed: 35776041
Anatol J Cardiol. 2022 Nov;26(11):832-840
pubmed: 35949125
Cardiovasc Diabetol. 2018 Nov 17;17(1):144
pubmed: 30447687
Anatol J Cardiol. 2015 Jan;15(1):61-2
pubmed: 25550249
N Engl J Med. 2022 Sep 22;387(12):1089-1098
pubmed: 36027570
J Am Coll Cardiol. 2009 Jun 16;53(24):2231-47
pubmed: 19520246
Turk Kardiyol Dern Ars. 2020 Apr;48(3):330-354
pubmed: 32281958
Eur Heart J. 2021 Sep 21;42(36):3727-3738
pubmed: 34448003
PLoS One. 2021 Feb 19;16(2):e0247234
pubmed: 33606763
Eur Heart J Cardiovasc Imaging. 2022 Sep 10;23(10):e333-e465
pubmed: 36017575
Anatol J Cardiol. 2016 Apr;16(4):299
pubmed: 27111202
Trends Pharmacol Sci. 2015 Jun;36(6):326-48
pubmed: 25895646
Turk Kardiyol Dern Ars. 2022 Oct;50(7):478-484
pubmed: 35976235
J Am Coll Cardiol. 2010 Jan 19;55(3):213-20
pubmed: 20117401
Int Immunopharmacol. 2022 Mar;104:108503
pubmed: 34998036
Anatol J Cardiol. 2021 Nov;25(11):821-828
pubmed: 34734816
Expert Opin Drug Saf. 2012 May;11 Suppl 1:S21-36
pubmed: 21635149
Circulation. 2022 Mar 29;145(13):1029-1031
pubmed: 35344407
Am Heart J. 2010 Sep;160(3):487.e1-7
pubmed: 20826257
Cardiovasc Diabetol. 2021 Jun 11;20(1):121
pubmed: 34116674
J Pharm Pharmacol. 2010 Dec;62(12):1776-83
pubmed: 21054405
Heart Rhythm. 2021 Jul;18(7):1098-1105
pubmed: 33757845
Cardiovasc Toxicol. 2021 Sep;21(9):747-758
pubmed: 34089496
N Engl J Med. 2015 Nov 26;373(22):2117-28
pubmed: 26378978
Turk Kardiyol Dern Ars. 2014 Apr;42(3):274-6
pubmed: 24769820
Anatol J Cardiol. 2015 Jan;15(1):56-60
pubmed: 25179886
Mol Cell Biochem. 2012 Apr;363(1-2):419-26
pubmed: 22203419
Anatol J Cardiol. 2016 Apr;16(4):234-41
pubmed: 26642465
Cardiovasc Diabetol. 2018 Jul 10;17(1):101
pubmed: 29991346
N Engl J Med. 2019 Nov 21;381(21):1995-2008
pubmed: 31535829
Andrologia. 2020 Aug;52(7):e13623
pubmed: 32364275