A person protected by a roxadustat shield from radiation.

Shielding Your Cells: How Roxadustat Could Be the Future of Radiation Protection

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Beau Callahan in Health & Wellness November 2025 • 4 min read.

"Discover how roxadustat (FG-4592), a novel PHD inhibitor, offers a promising shield against radiation-induced injuries, marking a new era in radioprotection."


In an era where the risks of radiation exposure are ever-present, from medical treatments to potential large-scale incidents, the quest for effective radioprotective measures is more critical than ever. Ionizing radiation poses a significant threat, leading to severe injuries, particularly in radiosensitive tissues such as the hematopoietic system. This system, responsible for the formation of blood cells, is vital for immune function and overall health.

Traditional approaches to mitigating radiation damage have often been limited by toxicity and other adverse effects. The need for innovative, safe, and highly effective radioprotective drugs has driven researchers to explore new avenues. Among these, prolyl hydroxylases domain (PHD) inhibitors have emerged as promising candidates, with initial studies suggesting their potential to protect against radiation-induced gastrointestinal toxicity.

Now, a new study shines a light on roxadustat (FG-4592), an oral PHD inhibitor already in use for treating anemia in patients with chronic kidney disease. This research reveals the protective effects of roxadustat against radiation-induced hematopoietic injuries, offering a beacon of hope for enhanced radioprotection strategies.

Unveiling Roxadustat's Radioprotective Power

A person protected by a roxadustat shield from radiation.

The study, conducted by researchers at the Faculty of Naval Medicine, Second Military Medical University in Shanghai, China, meticulously investigated the radioprotective effects of roxadustat both in vitro and in vivo. Their approach involved a range of sophisticated methods, from evaluating tissue injuries with Haematoxilin-Eosin (HE) staining to determining hematopoietic stem cells (HSCs) using flow cytometry. They also assessed cell apoptosis and DNA damage through various assays.

The findings were compelling: roxadustat pretreatment significantly increased the survival rate of irradiated mice, protecting their bone marrow and spleen from radiation-induced damage. The number of bone marrow cells (BMCs) and HSCs also increased in both irradiated mice and recipients after bone marrow transplantation (BMT). Moreover, roxadustat demonstrated its ability to shield cells from radiation-induced apoptosis and double-strand breaks of DNA.

Here’s a quick look at the key benefits highlighted in the study:
  • Increased survival rates in irradiated mice.
  • Protection of bone marrow and spleen from radiation damage.
  • Increased number of bone marrow cells and HSCs.
  • Protection against radiation-induced apoptosis and DNA damage.
These results underscore roxadustat's potential as a novel radioprotector, acting through the up-regulation of HIF-1α. Hypoxia-inducible factors (HIFs) are transcription factors that regulate the expression of genes related to reduced oxygen, playing a vital role in cellular response to hypoxia and stress. By modulating these factors, roxadustat appears to enhance the cells' resilience against radiation.

A Promising Future for Radiation Protection

The implications of this study are far-reaching. As a PHD inhibitor already approved for clinical use, roxadustat holds significant promise for translation into practical applications. Whether as a protective measure for individuals undergoing radiation therapy or as a countermeasure in the event of a radiological emergency, roxadustat offers a new avenue for mitigating the harmful effects of radiation. Further research and clinical trials will be essential to fully unlock its potential and establish its role in the future of radioprotection.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/jcmm.13937, Alternate LINK

Title: Radioprotective Effects Of Roxadustat (Fg-4592) In Haematopoietic System

Subject: Cell Biology

Journal: Journal of Cellular and Molecular Medicine

Publisher: Wiley

Authors: Pei Zhang, Jicong Du, Hainan Zhao, Ying Cheng, Suhe Dong, Yanyong Yang, Bailong Li, Fu Gao, Xuejun Sun, Jianming Cai, Cong Liu

Published: 2018-10-18

Everything You Need To Know

1

What is Roxadustat (FG-4592) and how does it work against radiation-induced injuries?

Roxadustat (FG-4592) is a prolyl hydroxylases domain (PHD) inhibitor initially used to treat anemia in chronic kidney disease patients. Recent research indicates that Roxadustat can protect against radiation-induced hematopoietic injuries. It achieves this by up-regulating HIF-1α, enhancing cellular resilience against radiation.

2

What methods were used to investigate the radioprotective effects of Roxadustat in the study?

The study, conducted by researchers at the Faculty of Naval Medicine, Second Military Medical University in Shanghai, China, utilized methods such as Haematoxilin-Eosin (HE) staining for evaluating tissue injuries and flow cytometry to determine hematopoietic stem cells (HSCs). They also assessed cell apoptosis and DNA damage through various assays to determine the protective effects of Roxadustat.

3

What are the key benefits of using Roxadustat as a radioprotector, according to the research?

Roxadustat pretreatment has been shown to increase survival rates in irradiated mice, protect the bone marrow and spleen from radiation damage, increase the number of bone marrow cells (BMCs) and HSCs, and shield cells from radiation-induced apoptosis and double-strand breaks of DNA. These protective effects make roxadustat a promising radioprotective agent.

4

How do Hypoxia-inducible factors (HIFs) play a role in Roxadustat's protection against radiation?

Hypoxia-inducible factors (HIFs) are transcription factors that regulate gene expression related to reduced oxygen levels, crucial for cellular response to hypoxia and stress. Roxadustat modulates these factors to enhance cells' resilience against radiation. This modulation is critical because it allows cells to better adapt and survive under radiation-induced stress.

5

What are the potential future applications of Roxadustat in radiation protection, and what further steps are needed?

The potential use of Roxadustat could extend to protecting individuals undergoing radiation therapy and serving as a countermeasure in radiological emergencies. Its clinical approval suggests a smoother path to practical application, though further research and clinical trials are necessary to fully understand and utilize its radioprotective capabilities. This could significantly improve outcomes for those exposed to harmful levels of radiation.

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