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遭受超致死全身或局部全身辐射的非人灵长类动物的组织病理学研究:一种医疗对策,γ-生育三烯酚的影响。

Histopathological studies of nonhuman primates exposed to supralethal doses of total- or partial-body radiation: influence of a medical countermeasure, gamma-tocotrienol.

机构信息

Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814-2712, USA.

Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

出版信息

Sci Rep. 2024 Mar 8;14(1):5757. doi: 10.1038/s41598-024-56135-w.


DOI:10.1038/s41598-024-56135-w
PMID:38459144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10923821/
Abstract

Despite remarkable scientific progress over the past six decades within the medical arts and in radiobiology in general, limited radiation medical countermeasures (MCMs) have been approved by the United States Food and Drug Administration for the acute radiation syndrome (ARS). Additional effort is needed to develop large animal models for improving the prediction of clinical safety and effectiveness of MCMs for acute and delayed effects of radiation in humans. Nonhuman primates (NHPs) are considered the animal models that reproduce the most appropriate representation of human disease and are considered the gold standard for drug development and regulatory approval. The clinical and histopathological effects of supralethal, total- or partial-body irradiations (12 Gy) of NHPs were assessed, along with possible protective actions of a promising radiation MCM, gamma-tocotrienol (GT3). Results show that these supralethal radiation exposures induce severe injuries that manifest both clinically as well as pathologically, as evidenced by the noted functionally crippling lesions within various major organ systems of experimental NHPs. The MCM, GT3, has limited radioprotective efficacy against such supralethal radiation doses.

摘要

尽管在过去的六十年中,医学领域和放射生物学领域取得了显著的科学进步,但美国食品和药物管理局仅批准了有限的辐射医学对策 (MCM) 用于急性辐射综合征 (ARS)。需要进一步努力开发大动物模型,以提高对 MCM 预防人类急性和延迟辐射效应的临床安全性和有效性的预测。非人类灵长类动物 (NHP) 被认为是最能重现人类疾病的动物模型,被认为是药物开发和监管批准的金标准。评估了 NHP 全身或部分全身照射(12Gy)的超高致死剂量、总致死剂量或亚致死剂量的临床和组织病理学影响,以及一种有前途的辐射 MCM γ-生育三烯酚 (GT3) 的可能保护作用。结果表明,这些超高致死剂量的辐射会导致严重的损伤,无论是在临床上还是在病理学上都表现出来,实验 NHP 的各种主要器官系统中明显出现功能障碍性损伤就是证明。MCM GT3 对这种超高致死剂量的辐射的放射防护效果有限。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/f75b911ae7f4/41598_2024_56135_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/eb638a299d00/41598_2024_56135_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/f30b7d687bd6/41598_2024_56135_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/37cd45a748a9/41598_2024_56135_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/a07f281b5096/41598_2024_56135_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/1731707bd708/41598_2024_56135_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/f75b911ae7f4/41598_2024_56135_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/eb638a299d00/41598_2024_56135_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/f30b7d687bd6/41598_2024_56135_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/37cd45a748a9/41598_2024_56135_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/a07f281b5096/41598_2024_56135_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/1731707bd708/41598_2024_56135_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f9/10923821/f75b911ae7f4/41598_2024_56135_Fig6_HTML.jpg

相似文献

[1]
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[3]
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[6]
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[7]
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[8]
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引用本文的文献

[1]
Pathology of acute sub-lethal or near-lethal irradiation of nonhuman primates prophylaxed with the nutraceutical, gamma tocotrienol.

Sci Rep. 2024-6-10

本文引用的文献

[1]
Modulation of Hematopoietic Injury by a Promising Radioprotector, Gamma-Tocotrienol, in Rhesus Macaques Exposed to Partial-Body Radiation.

Radiat Res. 2024-1-1

[2]
Survival and Hematologic Benefits of Romiplostim After Acute Radiation Exposure Supported FDA Approval Under the Animal Rule.

Int J Radiat Oncol Biol Phys. 2023-11-1

[3]
Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation.

BMC Genomics. 2023-5-22

[4]
Radiosensitivity of rhesus nonhuman primates: consideration of sex, supportive care, body weight, and age at time of exposure.

Expert Opin Drug Discov. 2023-7

[5]
The Radioprotectant, BIO 300, Protects the Lungs from Total-Body Irradiation Injury in C57L/J Mice.

Radiat Res. 2023-3-1

[6]
Development of gamma-tocotrienol as a radiation medical countermeasure for the acute radiation syndrome: current status and future perspectives.

Expert Opin Investig Drugs. 2023-1

[7]
Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model.

Int J Mol Sci. 2022-12-18

[8]
Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model.

Antioxidants (Basel). 2022-9-25

[9]
Determination of Lethality Curve for Cobalt-60 Gamma-Radiation Source in Rhesus Macaques Using Subject-Based Supportive Care.

Radiat Res. 2022-12-1

[10]
Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation.

Mol Ther Nucleic Acids. 2022-8-4

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