NAC Pre-Administration Prevents Cardiac Mitochondrial Bioenergetics, Dynamics, Biogenesis, and Redox Alteration in
Belén Cuevas-López1, Edgar Ignacio Romero-Ramirez1, Fernando E García-Arroyo1
1Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico.
Abstract:
The incidence of kidney disease is increasing worldwide. Acute kidney injury (AKI) can strongly favor cardio-renal syndrome (CRS) type 3 development. However, the mechanism involved in CRS development is not entirely understood. In this sense, mitochondrial impairment in both organs has become a central axis in CRS physiopathology. This study aimed to elucidate the molecular mechanisms associated with cardiac mitochondrial impairment and its role in CRS development in the folic acid-induced AKI (FA-AKI) model. Our results showed that 48 h after FA-AKI, the administration of N-acetyl-cysteine (NAC), a mitochondrial glutathione regulator, prevented the early increase in inflammatory and cell death markers and oxidative stress in the heart. This was associated with the ability of NAC to protect heart mitochondrial bioenergetics, principally oxidative phosphorylation (OXPHOS) and membrane potential, through complex I activity and the preservation of glutathione balance, thus preventing mitochondrial dynamics shifting to fission and the decreases in mitochondrial biogenesis and mass. Our data show, for the first time, that mitochondrial bioenergetics impairment plays a critical role in the mechanism that leads to heart damage. Furthermore, NAC heart mitochondrial preservation during an AKI event can be a valuable strategy to prevent CRS type 3 development.
Insights
N-acetyl-cysteine (NAC) protects heart mitochondria during acute kidney injury (AKI), preventing cardio-renal syndrome type 3. NAC preserves mitochondrial function and reduces inflammation, offering a potential therapeutic strategy.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Mitochondrial Medicine
Background:
- Global rise in kidney disease incidence.
- Acute kidney injury (AKI) is linked to cardio-renal syndrome (CRS) type 3.
- Mitochondrial dysfunction is implicated in CRS pathophysiology.
Purpose of the Study:
- Elucidate molecular mechanisms of cardiac mitochondrial impairment in folic acid-induced AKI (FA-AKI).
- Investigate the role of mitochondrial dysfunction in CRS development.
- Evaluate N-acetyl-cysteine (NAC) as a protective agent.
Main Methods:
- Induction of FA-AKI in a relevant animal model.
- Administration of NAC post-AKI.
- Assessment of cardiac mitochondrial bioenergetics, oxidative stress, inflammation, and cell death markers.
- Analysis of mitochondrial dynamics, biogenesis, and mass.
Main Results:
- FA-AKI increased cardiac inflammatory and cell death markers and oxidative stress.
- NAC administration prevented these early increases.
- NAC protected mitochondrial bioenergetics, including oxidative phosphorylation (OXPHOS) and membrane potential via Complex I.
- NAC preserved glutathione balance, mitochondrial dynamics, biogenesis, and mass.
Conclusions:
- Mitochondrial bioenergetics impairment is critical in AKI-induced heart damage.
- NAC protects cardiac mitochondria during AKI.
- NAC is a potential strategy to prevent CRS type 3 development.
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