Impact of Age, Sex, and Genetic Diversity in Murine Models of the Hematopoietic Acute Radiation Syndrome (H-ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE)

Orschell, Christie M.; Wu, Tong; Patterson, Andrea M.

doi:10.1007/s40778-022-00214-z

Cited by 7 publications

(6 citation statements)

References 120 publications

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“…Given the rapid secretion of ACTH from pituitary glands [29] and the short half-life of corticosterone in the blood of only a few hours in humans [42], lower corticosterone concentrations after one day would reflect fatigue in the steroidogenic ability of the cells in adrenal glands. Protection of the lower portion of the body by a lead shield causes a greater release of corticosterone and adrenal Asc in comparison with that under total-body irradiation in rats [2]. These observations demonstrate that exposure to X-rays first stimulates the release of ACTH from pituitary glands, which leads to the stimulation of corticosterone production [29].…”

Section: Discussionmentioning

confidence: 74%

“…Individuals exposed to radiation from either a nuclear accident or during a medical treatment are at risk of developing acute radiation syndrome, which characteristically occurs in hematopoietic, gastrointestinal, neurovascular, and cutaneous systems [1,2]. Reactive oxygen species (ROS) produced upon exposure to X-rays are major components of tumoricidal action during radiation therapy and are known to oxidatively damage normal tissues [3].…”

Section: Introductionmentioning

confidence: 99%

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Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice

Bo,

Nohara,

Yamada

et al. 2024

Antioxidants

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Bone marrow cells are the most sensitive to exposure to X-rays in the body and are selectively damaged even by doses that are generally considered permissive in other organs. Ascorbic acid (Asc) is a potent antioxidant that is reported to alleviate damages caused by X-ray exposure. However, rodents can synthesize Asc, which creates difficulties in rigorously assessing its effects in such laboratory animals. To address this issue, we employed mice with defects in their ability to synthesize Asc due to a genetic ablation of aldehyde reductase (Akr1a-KO). In this study, concentrations of white blood cells (WBCs) were decreased 3 days after exposure to X-rays at 2 Gy and then gradually recovered. At approximately one month, the recovery rate of WBCs was delayed in the Akr1a-KO mouse group, which was reversed via supplementation with Asc. Following exposure to X-rays, Asc levels decreased in plasma, bone marrow cells, and the liver during an early period, and then started to increase. X-ray exposure stimulated the pituitary gland to release adrenocorticotropic hormone (ACTH), which stimulated corticosterone secretion. Asc released from the liver, which was also stimulated by ACTH, appeared to be recruited to the bone marrow. Since corticosterone in high doses is injurious, these collective results imply that Asc protects bone marrow via its antioxidant capacity against ROS produced via exposure to X-rays and the cytotoxic action of transiently elevated corticosterone.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice

Bo,

Nohara,

Yamada

et al. 2024

Antioxidants

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“…Considering that male mice are more sensitive to radiation, we selected male C57BL/6J mice for this experiment [ 65 , 66 ]. Male C57BL/6J mice weighing 20 ± 2 g were purchased from Beijing Weitong Lihua Experimental Animal Technology, License No: SCK (Beijing) 2021-006.…”

Section: Methodsmentioning

confidence: 99%

Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice

Ru,

Zhang,

Shen

et al. 2023

IJMS

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The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening.

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“…The consequences in people who survive ARS or receive sublethal doses of IR are known as delayed effects of acute radiation exposure (DEARE) and mainly result from the late‐onset deterministic and stochastic effects of IR. Common DEARE outcomes include hematopoietic disorders, late hematopoietic injury, pulmonary injury, cataract formation, cognitive deficits, and renal damage 8–12 . The incidences of thyroid cancer and leukemia have been shown to increase in children, and there is evidence of sex‐specific differences in the risk and types of cancer caused by such exposure.…”

Section: Radiation Exposure and Injurymentioning

confidence: 99%

Development of radiation countermeasure agents for acute radiation syndromes

Guan,

Li,

Meng

2023

Anim Models and Exp Med

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The risk of internal and external exposure to ionizing radiation (IR) has increased alongside the development and implementation of nuclear technology. Therefore, serious security issues have emerged globally, and there has been an increase in the number of studies focusing on radiological prevention and medical countermeasures. Radioprotective drugs are particularly important components of emergency medical preparedness strategies for the clinical management of IR‐induced injuries. However, a few drugs have been approved to date to treat such injuries, and the related mechanisms are not entirely understood. Thus, the aim of the present review was to provide a brief overview of the World Health Organization's updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies. This review also discusses the types of radiation‐induced health injuries and the related mechanisms, as well as the development of various radioprotective agents, including Chinese herbal medicines, for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome.

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Impact of Age, Sex, and Genetic Diversity in Murine Models of the Hematopoietic Acute Radiation Syndrome (H-ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE)

Cited by 7 publications

References 120 publications

Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice

Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice

Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice

Development of radiation countermeasure agents for acute radiation syndromes

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