Title:Targeting Ferroptosis as a New Approach for Radiation Protection and
Mitigation
Volume: 19
Issue: 1
Author(s): Zahra Shaghaghi, Arsalan Salari, Fatemeh Jalali, Maryam Alvandi, Soghra Farzipour*Nasim Zarei Polgardani
Affiliation:
- Department of Cardiology, Cardiovascular Diseases Research
Center, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Radiopharmacy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
Keywords:
Ferroptosis, radiotherapy, radioprotector, normal cell toxicity, malignancies, ionizing radiation.
Abstract: Radiation-induced normal cell toxicity (RINCT) is a major factor to consider while
treating any ailment with radiotherapy. Clinical irradiation of tumors necessitates an understanding
of the potential efficacy of radiation protective agents in reducing radiation damage to healthy
tissues and their effects on tumor tissue radiosensitivity. Ferroptosis is a relatively new form of
iron-dependent cell death that has been linked to a variety of disease pathologies. The key mediators
of ferroptosis have been identified as lipid peroxidation and iron metabolism. Lipid peroxidation
is the result of a reaction between reactive oxygen (ROS) and reactive nitrogen species (RNS)
with phosphatidylethanolamine-containing polyunsaturated fatty acids (PUFAs). Ferroptosis inhibitors
have been demonstrated to have anti-inflammatory effects in animal models of disease. It
was recently shown that ionizing radiation (IR) generates severe ferroptosis, a critical component
of RT-mediated normal cell toxicity. These findings support the use of ferroptosis inhibitor treatments
for the treatment of radiation normal cell toxicity. Targeting lipid metabolic substrates and
controlling ferroptosis by radiation could reduce toxicity and improve clinical outcomes. In this
study, we address the relationships between radiotherapy and various types of radiation-induced
cell death, and we discuss the interactions between ferroptosis and other kinds of controlled cell
death generated by radiotherapy, and we investigate combination treatment options targeting ferroptosis
in radiotherapy. This review will be a foundation for future research on ferroptosis in radiotherapy.
Additionally, the relevant patents on ferroptosis inhibitors with various therapeutic
potentials have been discussed.
