Effective oral countermeasures against ionizing radiation-induced damagewithout hindering cancer radiotherapy
High-dose ionizing radiation induces severe multi-organ injury, yet no broadly effective, orally available countermeasure has been validated. Here we describe a fully oral, multi-component formulation comprising bioavailable polyphenol derivatives (pterostilbene cocrystals and silybin-phosphatidylch...
| Authors: | , , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2026 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:dnet:recercat____::71839b0c195d0be72386e68c0ff1a80c |
| Online Access: | https://hdl.handle.net/2445/229185 |
| Access Level: | Open access |
| Keyword: | Radioteràpia Radiació ionitzant Polifenols Radiotherapy Ionizing radiation Polyphenols |
| Summary: | High-dose ionizing radiation induces severe multi-organ injury, yet no broadly effective, orally available countermeasure has been validated. Here we describe a fully oral, multi-component formulation comprising bioavailable polyphenol derivatives (pterostilbene cocrystals and silybin-phosphatidylcholine), the NAD⁺ precursor nicotinamide riboside, and captopril, an angiotensin-converting enzyme inhibitor with established radiomitigative activity that synergizes with the polyphenols. This combination provides robust systemic radioprotection, enabling long-term survival in 90% of mice exposed to a lethal (LD50/30) dose of X-rays. Mechanistically, the formulation mitigates hematopoietic, intestinal, and neuromotor injury while enhancing DNA repair, suppressing oxidative stress, preserving NAD⁺ homeostasis, and activating autophagy. In intestinal epithelial cells, it markedly reduces radiation-induced apoptosis, inflammatory signaling, and mitochondrial dysfunction through coordinated modulation of Nrf2, NF-κB, and sirtuin-regulated stress responses. Critically, normal tissue protection does not compromise tumor control. In triple-negative breast cancer models, irradiation-induced tumor regression is preserved, whereas in glioblastoma (a typically radioresistant malignancy) tumor radiosensitivity is significantly enhanced via sustained oxidative stress, reduced PARP1 expression, and inhibition of HIF-1α and VEGF signaling. Collectively, these findings define an orally deployable, mechanistically integrated strategy that protects normal tissues while preserving or augmenting tumor radiosensitivity, supporting its translational potential as a practical and effective countermeasure against ionizing radiation exposure. |
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