Radiation damage to the lung: Mitigation by angiotensin-converting enzyme (ACE) inhibitors

Authors


  • The Authors: Dr. Meetha Medhora is an Associate Professor of Radiation Oncology, Medicine and Physiology. Feng Gao is a Post-Doctoral Fellow in the Department of Radiation Oncology. Elizabeth Jacobs is Professor of Pulmonary Medicine and Physiology, Associate Dean of Research at the Medical College of Wisconsin and Associate Chief of Staff (Zablocki Veterans' Affairs Medical Center, Milwaukee, USA). John Moulder is Professor of Radiation Oncology at the Medical College of Wisconsin, USA.

Meetha Medhora, MFRC 4076, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Email: medhoram@mcw.edu

ABSTRACT

Concern regarding accidental overexposure to radiation has been raised after the devastating Tohuku earthquake and tsunami which initiated the Fukushima Daiichi nuclear disaster in Japan in March 2011. Radiation exposure is toxic and can be fatal depending on the dose received. Injury to the lung is often reported as part of multi-organ failure in victims of accidental exposures. Doses of radiation >8 Gray to the chest can induce pneumonitis with right ventricular hypertrophy starting after ∼2 months. Higher doses may be followed by pulmonary fibrosis that presents months to years after exposure. Though the exact mechanisms of radiation lung damage are not known, experimental animal models have been widely used to study this injury. Rodent models for pneumonitis and fibrosis exhibit vascular, parenchymal and pleural injuries to the lung. Inflammation is a part of the injuries suggesting involvement of the immune system. Researchers worldwide have tested a number of interventions to prevent or mitigate radiation lung injury. One of the first and most successful class of mitigators are inhibitors of angiotensin-converting enzyme (ACE), an enzyme that is abundant in the lung. These results offer hope that lung injury from radiation accidents may be mitigated, since the ACE inhibitor captopril was effective when started up to 1 week after irradiation.

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