Evaluate the effect of dapagliflozin in the prevention of doxorubicin-induced acute cardiotoxicity in rats

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Research Paper 03/02/2024
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Evaluate the effect of dapagliflozin in the prevention of doxorubicin-induced acute cardiotoxicity in rats

Ola Sadeq Al-Shimaysawee, Fadhil A. Rizij, Rafid Mohammed Ali Hassan Wasfi
Int. J. Biosci.24( 2), 1-9, February 2024.
Certificate: IJB 2024 [Generate Certificate]

Abstract

Cancer ranks second in frequency among non-communicable diseases after cardiovascular disorders. The increased life expectancy has made cancers more common, making it crucial to avoid side effects of the medications used to treat them. SGLT2i medications lower the risk of significant cardiovascular events and heart failure-related hospitalizations, as shown in clinical trials. Dapagliflozin is one such medication that is primarily regulated by blood glucose levels but may also impact cardiac disorders through other processes. This study will evaluate the potential protective effects of Dapagliflozin on DOX-induced cardiotoxicity in female rats, manifested by changes in biochemical parameters in tissue and serum samples, histopathological differences, and compare their changes. Twenty-four rats were divided into three weight-based groups. The first group received saline, the second group received doxorubicin, and the third group received dapagliflozin for three days before receiving doxorubicin for two weeks. Doxorubicin causes cardiotoxicity, as evidenced by increased caspase-3 and inflammatory markers. Dapagliflozin reduces cardiotoxicity by increasing SOD and GSH and decreasing caspase 3, as well as improving the CMYO score and lesions. Dapagliflozin successfully mitigated DOX-induced cardiotoxicity in rats at the concentrations utilized in this investigation. This phenomenon potentially pertains to inhibiting and safeguarding against oxidative stress, the pathway of apoptosis, and the inflammatory response.

VIEWS 314

Abdulkareem Aljumaily SA., Demir M, Elbe H, Yigitturk G, Bicer Y, Altinoz E. 2021. Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats. Environmental Science and Pollution Research International 28(46), 65802–65813. https://doi.org/10.1007/s11356-021-15409-w.

Albakaa RN, Rizij FA, Hassan RMA. 2023. Potential Role of Empagliflozin to Ameliorate Doxorubicin Induced Cardiotoxicity in Male Rats. DOI: 10.26655/JMCHEMSCI.2023.3.18

Alyasiry E, Janabi A, Hadi N. 2022. Dipyridamole ameliorates doxorubicin-induced cardiotoxicity. Journal of Medicine and Life 15(9), 1184–1190. https://doi.org/10.25122/jml-2021-0199.

Antonucci S, Di Sante M, Tonolo F, Pontarollo L, Scalcon V, Alanova P, Menabò R, Carpi A, Bindoli A, Rigobello MP, Giorgio M, Kaludercic N, Di Lisa F. 2021. The Determining Role of Mitochondrial Reactive Oxygen Species Generation and Monoamine Oxidase Activity in Doxorubicin-Induced Cardiotoxicity. Antioxidants and Redox Signaling, 34(7), 531–550.

Aryal B, Rao VA. 2016. Deficiency in Cardiolipin Reduces Doxorubicin-Induced Oxidative Stress and Mitochondrial Damage in Human B-Lymphocytes. PloSone 11(7), e0158376.

Aziz MM, Abd El Fattah MA, Ahmed KA, Sayed HM. 2020. Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats. Canadian Journal of Physiology and Pharmacology 98(4), 183-193. https://doi.org/10.1139/cjpp-2019-0299

Belen E, Canbolat IP, Yigittürk G, Cetinarslan Ö, Akdeniz CS, Karaca M, Sönmez M, Erbas O. 2022. Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats. European Review for Medical and Pharmacological Sciences 26(12), 4403–4408. https://doi.org/10.26355/eurrev_202206_29079

Bertero E, Prates Roma L, Ameri P, Maack C. 2018. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovascular Research 114(1), 12-18. https://doi.org/10.1093/cvr/cvx149.

Chang WT, Lin YW, Ho CH, Chen ZC, Liu PY, Shih JY. 2021. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients. Archives of Toxicology 95(2), 659–671.

Chen H, Tran D, Yang HC, Nylander S, Birnbaum Y, Ye Y. 2020. Dapagliflozin and Ticagrelor Have Additive Effects on the Attenuation of the Activation of the NLRP3 Inflammasome and the Progression of Diabetic Cardiomyopathy: an AMPK-mTOR Interplay. Cardiovascular Drugs and Therapy 34(4), 443–461. https://doi.org/10.1007/s10557-020-06978-y

Chen W, Zhang Y, Wang Z, Tan M, Lin J, Qian X, Li H, Jiang T. 2023. Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosis via MAPK signaling inhibition. Frontiers in Pharmacology 14, 1078205.

Dimitriadis GK, Nasiri-Ansari N, Agrogiannis G, Kostakis ID, Randeva MS, Nikiteas N, Patel VH, Kaltsas G, Papavassiliou AG, Randeva HS, Kassi E. 2019. Empagliflozin improves primary haemodynamic parameters and attenuates the development of atherosclerosis in high fat diet fed APOE knockout mice. Molecular and Cellular Endocrinology 494, 110487. https://doi.org/10.1016/j.mce.2019.110487

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray, F. 2013. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. European Journal of Cancer (Oxford, England: 1990) 49(6), 1374-1403. https://doi.org/10.1016/j.ejca.2012.12.027.

Hasan FM, Alsahli M, Gerich JE. 2014. SGLT2 inhibitors in the treatment of type 2 diabetes. Diabetes Research and Clinical Practice 104(3), 297-322. https://doi.org/10.1016/j.diabres.2014.02.014

Hassani Moghadam F, Taher MA, Karimi-Maleh H. 2021. Doxorubicin Anticancer Drug Monitoring by ds-DNA-Based Electrochemical Biosensor in Clinical Samples. Micromachines 12(7), 808. https://doi.org/10.3390/mi12070808

Hekmat AS, Navabi Z, Alipanah H, Javanmardi K. 2021. Alamandine significantly reduces doxorubicin-induced cardiotoxicity in rats. Human and Experimental Toxicology 40(10), 1781-1795. https://doi.org/10.1177/09603271211010896

Hsia DS, Grove O, Cefalu WT. 2017. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Current Opinion in Endocrinology, Diabetes, and Obesity 24(1), 73–79. https://doi.org/10.1371/journal.pone.0158376.

Jiang X, Wang X. 2004. Cytochrome C-mediated apoptosis. Annual Review of Biochemistry 73, 87-106. https://doi.org/10.1146/annurev.biochem.73.011303

Ko SF, Sung PH, Yang CC, Chiang JY, Yip HK. 2023. Combined therapy with dapagliflozin and entresto offers an additional benefit on improving the heart function in rat after ischemia-reperfusion injury. Biomedical Journal 46(3), 100546. https://doi.org/10.1016/j.bj.2022.06.002

Lahnwong S, Chattipakorn SC, Chattipakorn N. 2018. Potential mechanisms responsible for cardioprotective effects of sodium-glucose co-transporter 2 inhibitors. Cardiovascular Diabetology 17(1), 101. https://doi.org/10.1186/s12933-018-0745-5

Lahnwong S, Palee S, Apaijai N, Sriwichaiin S, Kerdphoo S, Jaiwongkam T, Chattipakorn SC, Chattipakorn N. 2020. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovascular Diabetology 19(1), 91. https://doi.org/10.1186/s12933-020-01066-9.

Liu C, Ma X, Zhuang J, Liu L, Sun C. 2020. Cardiotoxicity of doxorubicin-based cancer treatment: What is the protective cognition that phytochemicals provide US. Pharmacological Research 160, 105062. https://doi.org/10.1016/j.phrs.2020.105062

Ma H, Kong J, Wang YL, Li JL, Hei NH, Cao XR, Yang JJ, Yan WJ, Liang WJ, Dai HY, Dong B. 2017. Angiotensin-converting enzyme 2 overexpression protects against doxorubicin-induced cardiomyopathy by multiple mechanisms in rats. Oncotarget 8(15), 24548–24563. https://doi.org/10.18632/oncotarget.15595

Mobaraki M, Faraji A, Zare M, Dolati P, Ataei M, Manshadi HD. 2017. Molecular mechanisms of cardiotoxicity: a review on major side-effect of doxorubicin. Indian J. Pharm. Sci. 79, 335-344.

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, DAPA-HF Trial Committees and Investigators. 2019. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. The New England journal of Medicine 381(21), 1995-2008. https://doi.org/10.1056/NEJMoa1911303

Nicol M, Sadoune M, Polidano E, Launay JM, Samuel JL, Azibani F, Cohen-Solal A. 2021. Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol. ESC Heart Failure 8(2), 928-937. https://doi.org/10.1002/ehf2.13198

Oliveira MS, Melo MB, Carvalho JL, Melo IM, Lavor MS, Gomes DA, de Goes AM, Melo MM. 2013. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography. Journal of Cancer Science and Therapy 5(2), 52–57. https://doi.org/10.4172/1948-5956.1000184

Oner Z, Altınoz E, Elbe H, Ekinci N. 2019. The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats. Human and Experimental Toxicology 38(7), 803-813. DOI: 10.1177/0960327119842634

Pizzino F, Vizzari G, Bomzer CA, Qamar R, Carerj S, Zito C, Khandheria BK. 2014. Diagnosis of Chemotherapy-induced Cardiotoxicity. J Patient Cent Res Rev. 1, 121-27.

Plosker GL. 2014. Dapagliflozin: a review of its use in patients with type 2 diabetes. Drugs 74(18), 2191–2209. https://doi.org/10.1007/s40265-014-0324-3

Reis-Mendes A, Padrão AI, Duarte JA, Gonçalves-Monteiro S, Duarte-Araújo M, Remião F, Carvalho F, Sousa E, Bastos ML, Costa VM. 2021. Role of Inflammation and Redox Status on Doxorubicin-Induced Cardiotoxicity in Infant and Adult CD-1 Male Mice. Biomolecules 11(11), 1725. https://doi.org/10.3390/biom11111725

Scheen AJ. 2015. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 75(1), 33–59. https://doi.org/10.1007/s40265-014-0337-y

Scheen AJ. 2020. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nature reviews. Endocrinology 16(10), 556–577. https://doi.org/10.1038/s41574-020-0392-2

Shibusawa R, Yamada E, Okada S, Nakajima Y, Bastie CC, Maeshima A, Kaira K, Yamada M. 2019. Dapagliflozin rescues endoplasmic reticulum stress-mediated cell death. Scientific reports, 9(1), 9887. https://doi.org/10.1038/s41598-019-46402-6

Spigoni V, Fantuzzi F, Carubbi C, Pozzi G, Masselli E, Gobbi G, Solini A, Bonadonna RC, Dei Cas A. 2020. Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: potential relevance to prevention of cardiovascular events. Cardiovascular Diabetology 19(1), 46. https://doi.org/10.1186/s12933-020-01016-5

Wang L, Zhang TP, Zhang Y, Bi HL, Guan XM, Wang HX, Wang X, Du J, Xia YL, Li HH. 2016. Protection against doxorubicin-induced myocardial dysfunction in mice by cardiac-specific expression of carboxyl terminus of hsp70-interacting protein. Scientific Reports 6, 28399. https://doi.org/10.1038/srep28399

Wilding J, Fernando K, Milne N, Evans M, Ali A, Bain S, Hicks D, James J, Newland-Jones P, Patel D, Viljoen A. 2018. SGLT2 Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for Clinical Practice. Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders 9(5), 1757–1773. https://doi.org/10.1007/s13300-018-0471-8

World Health Organization. Available at: https:// www.who.int/news-room/fact-sheets/detail/noncommunicable- diseases.

Wu S, Ko YS, Teng MS, Ko YL, Hsu LA, Hsueh C, Chou YY, Liew CC, Lee YS. 2002. Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: In vitro and in vivo studies. Journal of Molecular and Cellular Cardiology 34(12), 1595–1607. https://doi.org/10.1006/jmcc.2002.2110

Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, Durand JB, Gibbs H, Zafarmand AA, Ewer MS. 2004. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation 109(25), 3122–3131. https://doi.org/10.1161/01.CIR.0000133187.74800.B9