4.3 Article

Effect of Radiation on the Essential Nutrient Homeostasis and Signaling of Retinoids in a Non-human Primate Model with Minimal Bone Marrow Sparing

Journal

HEALTH PHYSICS
Volume 121, Issue 4, Pages 406-418

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HP.0000000000001477

Keywords

biological indicators; radiation damage; radiation; ionizing; partial body irradiation

Funding

  1. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201000046C, HHSN272201500013I]
  2. University of Maryland School of Pharmacy Mass Spectrometry Center [SOP1841-IQB2014]

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High-dose radiation exposure can lead to hematopoietic and gastrointestinal acute radiation syndromes, followed by delayed effects such as damage to various tissues and inflammation. Radiation may disrupt retinoid metabolism, playing a crucial role in inhibiting inflammation and fibrosis development.
High-dose radiation exposure results in hematopoietic (H) and gastrointestinal (GI) acute radiation syndromes (ARS) followed by delayed effects of acute radiation exposure (DEARE), which include damage to lung, heart, and GI. Whereas DEARE includes inflammation and fibrosis in multiple tissues, the molecular mechanisms contributing to inflammation and to the development of fibrosis remain incompletely understood. Reports that radiation dysregulates retinoids and proteins within the retinoid pathway indicate that radiation disrupts essential nutrient homeostasis. An active metabolite of vitamin A, retinoic acid (RA), is a master regulator of cell proliferation, differentiation, and apoptosis roles in inflammatory signaling and the development of fibrosis. As facets of inflammation and fibrosis are regulated by RA, we surveyed radiation-induced changes in retinoids as well as proteins related to and targets of the retinoid pathway in the non-human primate after high dose radiation with minimal bone marrow sparing (12 Gy PBI/BM2.5). Retinoic acid was decreased in plasma as well as in lung, heart, and jejunum over time, indicating a global disruption of RA homeostasis after IR. A number of proteins associated with fibrosis and with RA were significantly altered after radiation. Together these data indicate that a local deficiency of endogenous RA presents a permissive environment for fibrotic transformation.

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