Supplemental deinoxanthin protects mice from irradiation-mediated systemic impairments by recovering hematopoietic and degenerative complications

ABSTRACT: Total body irradiation (TBI) is used as curative therapy for cancer patients and in bone marrow (BM) transplantation. However, TBI impairs organs and BM and dysregulates the fates of BM-residing hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Studies have suggested that TBI-mediated systemic injuries might be improved by preventing the overproduction of reactive oxygen species (ROS) and inflammatory mediators. In this work, we investigated whether Deinococcus radiodurans-derived deinoxanthin (DEIX) protects mice from sub-lethal TBI (5 Gy)-mediated complications and elucidated the associated mechanisms. Long-term oral supplementation with DEIX (25 mg/kg body weight, once per day for 42 consecutive days) protected mice against TBI-mediated decreases in organ and body weights, lifespan, and bone mass accrual. Supplemental DEIX inhibited TBI-mediated structural damage in the liver, kidney, and spleen and restored endogenous antioxidant defense systems in the liver and BM of TBI-exposed mice. Supplemental DEIX also suppressed BM impairment and the induction of senescence in BM-conserved HSCs and MSCs in TBI-exposed mice. That suppression involved the DEIX-induced restoration of TBI-stimulated disorder in osteogenic, osteoclastogenic, and adipogenic activation in BM. Additionally, supplemental DEIX recovered TBI-mediated defects in hematopoietic development and the multipotent functions of BM-derived cells. Moreover, the direct addition of DEIX in vitro diminished ROS accumulation and osteoclast formation and stimulated the proliferation and mineralization of BM-derived cells. Collectively, this study introduces the protective role of DEIX in TBI-mediated systemic defects and supports its clinical usefulness for patients who require TBI.

ORGANISM(S): Mus musculus

PROVIDER: GSE301666 | GEO | 2026/01/01

REPOSITORIES: GEO