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The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2024 Jul 25; Vol. 19, pp. 7567-7583. Date of Electronic Publication: 2024 Jul 25 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Background: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer's (AR) and Lactate Ringer's solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.<br />Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.<br />Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats' survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.<br />Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.<br />Competing Interests: The authors report no conflicts of interest in this work.<br /> (© 2024 Tan et al.)
- Subjects :
- Animals
Rats
Male
Resuscitation methods
Rats, Sprague-Dawley
Cell Line
Phospholipid Hydroperoxide Glutathione Peroxidase metabolism
Cyclooxygenase 2 metabolism
Lipid Peroxidation drug effects
Oxidative Stress drug effects
Shock, Hemorrhagic drug therapy
Shock, Hemorrhagic therapy
Ferroptosis drug effects
Myocytes, Cardiac drug effects
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 19
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 39081897
- Full Text :
- https://doi.org/10.2147/IJN.S463121