Title:Redox Interactions in Chemo/Radiation Therapy-induced Lung Toxicity; Mechanisms and Therapy Perspectives
Volume: 23
Issue: 13
Author(s): Xixi Lai*Masoud Najafi*
Affiliation:
- The Department of Respiratory and Critical Medicine, Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
Keywords:
Lung, reduction/oxidation (Redox), pneumonitis, fibrosis, reactive oxygen species (ROS), cytokines.
Abstract: Lung toxicity is a key limiting factor for cancer therapy, especially lung, breast, and
esophageal malignancies. Radiotherapy for chest and breast malignancies can cause lung injury.
However, systemic cancer therapy with chemotherapy may also induce lung pneumonitis and fibrosis.
Radiotherapy produces reactive oxygen species (ROS) directly via interacting with water molecules
within cells. However, radiation and other therapy modalities may induce the endogenous
generation of ROS and nitric oxide (NO) by immune cells and some nonimmune cells such as fibroblasts
and endothelial cells. There are several ROS generating enzymes within lung tissue.
NADPH Oxidase enzymes, cyclooxygenase-2 (COX-2), dual oxidases (DUOX1 and DUOX2), and
the cellular respiratory system in the mitochondria are the main sources of ROS production following
exposure of the lung to anticancer agents. Furthermore, inducible nitric oxide synthase (iNOS)
has a key role in the generation of NO following radiotherapy or chemotherapy. Continuous generation
of ROS and NO by endothelial cells, fibroblasts, macrophages, and lymphocytes causes apoptosis,
necrosis, and senescence, which lead to the release of inflammatory and pro-fibrosis cytokines.
This review discusses the cellular and molecular mechanisms of redox-induced lung injury
following cancer therapy and proposes some targets and perspectives to alleviate lung toxicity.
