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Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as Visualized by a Two-Photon

Xilei Xie1, Fuyan Tang1, Guangzhao Liu1

  • 1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science , Shandong Normal University , Jinan 250014 , PR China.

Analytical Chemistry
|September 11, 2018
PubMed

Insights

Anthracycline chemotherapy can cause heart damage. A new fluorescent probe detects early mitochondrial peroxynitrite (ONOO-) buildup, identifying cardiotoxicity risk before symptoms appear.

Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Molecular Imaging

Background:

  • Anthracyclines are potent anticancer drugs but cause cardiotoxicity.
  • Early diagnosis and understanding the mechanism of anthracycline cardiotoxicity remain challenging.
  • Mitochondrial dysfunction is implicated in drug-induced heart damage.

Purpose of the Study:

  • To develop a novel fluorescent probe for detecting peroxynitrite (ONOO-).
  • To investigate the role of mitochondrial ONOO- in anthracycline cardiotoxicity.
  • To establish ONOO- as an early biomarker for subclinical cardiotoxicity.

Main Methods:

  • Fabrication of a two-photon-excitable, near-infrared-emissive fluorescent probe (TPNIR-FP).
  • Demonstration of TPNIR-FP's specificity, sensitivity, and rapid response to ONOO-.
  • Utilizing TPNIR-FP in cardiomyocyte and mouse models to monitor mitochondrial ONOO- levels.

Main Results:

  • TPNIR-FP exhibits high specificity and sensitivity for ONOO- with mitochondria-targeting ability.
  • Mitochondrial ONOO- levels were found to be upregulated in the early stages of anthracycline treatment.
  • Increased ONOO- correlated with the onset and progression of cardiotoxicity in experimental models.

Conclusions:

  • Mitochondrial peroxynitrite is a key contributor to anthracycline cardiotoxicity.
  • TPNIR-FP serves as a valuable tool for early detection of cardiotoxicity.
  • This probe offers insights into ONOO--related pathophysiological processes.

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