The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2024 Jul 31

PMID 39081897

Authors

Lei Tan

Han She

Yi Wang

Yuanlin Du

Jun Zhang

Yunxia Du

Yinyu Wu

Wei Chen

Bingqiang Huang

Duanyang Long

Xiaoyong Peng

Qinghui Li

Qingxiang Mao

Tao Li

Yi Hu

Affiliations

Soon will be listed here.

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.

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.

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.

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.

Citing Articles

Hemorrhagic Shock and Mitochondria: Pathophysiology and Therapeutic Approaches.

Andrianova N, Buyan M, Brezgunova A, Cherkesova K, Zorov D, Plotnikov E Int J Mol Sci. 2025; 26(5).

PMID: 40076469 PMC: 11898946. DOI: 10.3390/ijms26051843.

Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.

Ru Q, Li Y, Zhang X, Chen L, Wu Y, Min J Bone Res. 2025; 13(1):27.

PMID: 40000618 PMC: 11861620. DOI: 10.1038/s41413-024-00398-6.

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