Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity

Ulusan, Sebahat

doi:10.14744/anatoljcardiol.2023.2825

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…Previous studies have reported that SGLT2 inhibitors such as dapagliflozin have a beneficial effect in doxorubicin-induced cardiotoxicity [24][25][26]. Empagliflozin also improves cardiotoxicity injured by doxorubicin [27][28][29].…”

Section: Discussionmentioning

confidence: 97%

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

Cha,

Park,

Yoo

et al. 2024

Kidney Blood Press Res

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Introduction: Sodium–glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. Methods: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. Results: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interstingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. Conclusion: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms.

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Section: Discussionmentioning

confidence: 97%

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

Cha,

Park,

Yoo

et al. 2024

Kidney Blood Press Res

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“…Dapagliflozin also exhibited substantial cardioprotective effects against DOX cardiotoxicity. 44 , 45 , 46 , 47 , 48 , 50 , 51 , 52 , 53 Dapagliflozin improved ejection fraction and fractional shortening, 44 , 46 , 47 , 48 , 50 , 52 , 53 mitigated DOX-induced hemodynamic declines (+dP/dt and −dP/dt), and reduced LV internal dimensions at end-diastole and end-systole. 44 , 50 Additionally, it successfully reversed DOX-induced electrocardiographic changes.…”

Section: Sglt2 Inhibitors In Cardio-oncologymentioning

confidence: 94%

“…Subsequent to landmark studies demonstrating the cardioprotective effects of SGLT2 inhibitors in HF, numerous in vivo ( Table 2 ) and in vitro ( Table 3 ) studies, starting in 2019, have underscored the cardioprotective roles of SGLT2 inhibitors in mitigating cardiotoxicity induced by various cancer treatments, including DOX, 17 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 sunitinib, 20 trastuzumab, 21 cisplatin, 19 ipilmumab, 54 , 55 ponatinib, 56 and carfilzomib. 57 DOX has received particular attention because of its status as the most cardiotoxic cancer treatment and its widespread use.…”

Section: Sglt2 Inhibitors In Cardio-oncologymentioning

confidence: 99%

“… 32 Researchers have investigated several models of DOX cardiotoxicity, including acute 39 , 42 , 43 , 48 , 51 and chronic 17 , 39 , 41 , 46 , 47 , 48 cardiotoxicity, cardiorenal syndrome, 40 and conditions involving diabetic 44 and nondiabetic rodents. Empagliflozin 17 , 20 , 21 , 39 , 40 , 41 , 42 , 43 , 49 , 55 , 56 and dapagliflozin 44 , 45 , 46 , 48 , 50 , 51 , 52 , 53 , 54 , 56 have emerged as the most commonly used SGLT2 inhibitors, followed by canagliflozin. 19 , 57 Notably, no in vivo studies have reported the protective effects of canagliflozin against DOX, with only 1 in vivo study reporting the cardioprotective effects of canagliflozin against cisplatin 19 and an in vitro study demonstrating its efficacy against carfilzomib.…”

Section: Sglt2 Inhibitors In Cardio-oncologymentioning

confidence: 99%

“… DAPA (0.9 mg/kg/d for 8 d, oral gavage) Reversed DOX ECG changes ↓ CK-MB, AST Quagliariello et al (2023) 52 Female C57BL/6 mice DOX (2.17 mg/kg for 10 d, i.p.) DAPA (12 mg/kg/d, oral gavage) ↑ EF ↓ Cardiac NLRP3, MyD88, DAMPs, and NF-κB ↓ Inflammatory markers (IL-1β, IL-6, TNF-α, G-CSF, and GM-CSF) ↑ Phosphorylated AMPK ↓ Calgranulin S100 and galectine-3 ↓ Myocardial and renal NF-κB Ulusan et al (2023) 53 Male Wistar albino rats DOX (2.15 mg/kg, every 3 d for 21 d, i.p.) DAPA (10 mg/kg/d, oral gavage) ↑ EF ↓ Prolongation of QRS, QT Ren et al (2021) 20 Male C57BL/6J Sunitinib (40 mg/kg/d for 28 consecutive days, oral gavage) EMPA (10 mg/kg/d for 28 consecutive days, oral gavage) ↓ HTN ↑ EF, FS Reversed left ventricular systolic and diastolic dysfunction ↑ CFR ↓ cTnT, pro-BNP levels Autophagy restoration ↑ AMPK-mTOR signaling pathway Min et al (2023) 21 Male C57BL/6J mice Trastuzumab (10 mg/kg, once a week for 6 wk, i.p.)…”

Section: Sglt2 Inhibitors In Cardio-oncologymentioning

confidence: 99%

See 2 more Smart Citations

The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors

Dabour,

George,

Daniel

et al. 2024

JACC: CardioOncology

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Sodium-Glucose Cotransporter 2 Inhibitors During Cancer Therapy: Benefits, Risks, and Ongoing Clinical Trials

Osataphan,

Abdel-Qadir,

Zebrowska

et al. 2024

Curr Oncol Rep

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Purpose of review The goal of this paper is to summarize the data pertaining to the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) for the prevention of cardiotoxicity in patients receiving anthracyclines for cancer treatment. We discuss the potential efficacy of this class of medications, incorporating insights from existing literature and ongoing studies. Recent findings SGLT2i are a class of medications which were initially developed for treatment of Type 2 diabetes and later extended to treat heart failure with reduced and preserved ejection fraction regardless of diabetes status. There remains a need for effective and safe treatments to preventing cardiotoxicity in anthracycline-treated patients. It has been proposed that SGLT2i may provide protection against the cardiotoxic effects of anthracyclines. Some of the proposed mechanisms include beneficial metabolic, neurohormonal, and hemodynamic effects, renal protection, as well as a decrease in inflammation, oxidative stress, apoptosis, mitochondrial dysfunction and ion homeostasis. Summary There is emerging evidence from basic science and observational studies that SGLT2i may play a role in the prevention of chemotherapy-induced cardiotoxicity. Randomized controlled trials are needed to conclusively determine the role of SGLT2 inhibitors as a cardioprotective therapy in patients receiving anthracyclines for the treatment of cancer.

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Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity

Cited by 9 publications

References 33 publications

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice

The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors

Sodium-Glucose Cotransporter 2 Inhibitors During Cancer Therapy: Benefits, Risks, and Ongoing Clinical Trials

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