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Canagliflozin attenuates post-resuscitation myocardial dysfunction in diabetic rats by inhibiting autophagy through the PI3K/Akt/mTOR pathway
- Source :
- iScience, Vol 27, Iss 8, Pp 110429- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- Summary: This study investigated the effects of canagliflozin on myocardial dysfunction after cardiac arrest and cardiopulmonary resuscitation in diabetic rats and the underlying mechanisms. Male rats with type 2 diabetes mellitus (T2DM) were subjected to a modified epicardial fibrillation model. Pretreatment with canagliflozin (10 mg/kg/day) for four weeks improved ATP levels, post-resuscitation ejection fraction, acidosis, and hemodynamics. Canagliflozin also reduced myocardial edema, mitochondrial damage and, post-resuscitation autophagy levels. In vitro analyses showed that canagliflozin significantly reduced reactive oxygen species and preserved mitochondrial membrane potential. Using the PI3K/Akt pathway inhibitor Ly294002, canagliflozin was shown to attenuate hyperautophagy and cardiac injury induced by high glucose and hypoxia-reoxygenation through activation of the PI3K/Akt/mTOR pathway. This study highlights the therapeutic potential of canagliflozin in post-resuscitation myocardial dysfunction in diabetes, providing new insights for clinical treatment and experimental research.
- Subjects :
- cardiovascular medicine
human metabolism
Science
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 27
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bdddc9806dc54d1abad26bb5ddc27052
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2024.110429