Magnesium Ion-Doped Mesoporous Bioactive Glasses Loaded with Gallic Acid Against Myocardial Ischemia/Reperfusion Injury by Affecting the Biological Functions of Multiple Cells

Int J Nanomedicine. 2024 Jan 12:19:347-366. doi: 10.2147/IJN.S444751. eCollection 2024.

Abstract

Introduction: Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function.

Methods: Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg2+ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA.

Results: We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg2+ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors.

Conclusion: MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.

Keywords: gallic acid; macrophage polarization; magnesium ion; mesoporous bioactive glass; myocardial ischemia/reperfusion injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Gallic Acid / pharmacology
  • Magnesium
  • Mice
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / prevention & control
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Magnesium
  • Gallic Acid
  • Antioxidants
  • Anti-Inflammatory Agents

Grants and funding

This work was funded by the National Natural Science Foundation of China (grant no. 82270382, 82170505, 82200534), the Natural Science Foundation of Jiangxi Province (grant no. 20204BCJ22028, 20212ACB206020, 20203BBGL73141 and 20192BAB205070), the Natural Science Foundation of Hubei Province (2023AFB817), Key Research and Development Project of Hubei Provincial Department of Science and Technology (2023BCB002), Wuhan Talent’s Industry-Leading Talent Project (WHYCCYLJ2021002), the talent Project of Zhongnan Hospital of Wuhan University (grant no. rcyj20210601, xkjs202002, CXPY2022046).