PEG-G-CSF and L-Citrulline Combination Therapy for Mitigating Skin Wound Combined Radiation Injury in a Mouse Model

Wang, Li; Zhai, Min; Lin, Bin; Cui, Wanchang; Hull, Lisa; Li, Xianghong; Anderson, Marsha N.; Smith, Julian C.; Umali, M V; Jiang, Suping; Kiang, Juliann G.; Xiao, Mang

doi:10.1667/rade-20-00151.1

Cited by 12 publications

(30 citation statements)

References 42 publications

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“…Animals were obtained from the Jackson Laboratory (Bar Harbor, ME, USA) and were 13-15 weeks old at time of use. The reason we chose female mice is that male mice are more likely to sustain unnecessary injuries because they are more aggressive when housed together, as described [21]. All mice were required to acclimate to their new surroundings for at least 72 h after arrival.…”

Section: Micementioning

confidence: 99%

“…Female mice, 24-25 g of average body weight and around 14-15 weeks old, were exposed to total body irradiation (TBI) from a bilateral radiation field at AFRRI's 60 Co facility, as previously described [21]. To determine dose rates (to water) in the cores of acrylic mouse phantoms, we employed an alanine/electron spin resonance (ESR) dosimetry system (American Society for Testing and Materials, Standard E 1607; ASTI International, Philadelphia, PA, USA).…”

Section: Total Body Irradiationmentioning

confidence: 99%

“…The wounding procedure comprises 2 steps, the skin shaving and skin wounding, both of which were conducted under anesthesia by isoflurane inhalation, as described [21]. To prepare for wounding, the dorsal fur was shaved using an electric hair clipper two-three days prior to TBI.…”

Section: Skin Woundingmentioning

confidence: 99%

“…To improve the preparedness for attacks using radiation devices of mass destruction, and, particularly, to promote the development of MCMs for mitigating/treating RCI, several animal models for different types of RCI have been established [1]. At the Armed Forces Radiobiology Research Institute (AFRRI), a mouse model of total body irradiation (TBI), combined with a full-thickness, non-lethal skin wound (SW), was developed and has been extensively used in screening potential MCMs against RCI [5,7,[10][11][12][13][14][15][16][17][18][19][20][21]. Studies using this mouse model first demonstrated that RCI dramatically increases the 30-day mortality and decreases radiation LD 50/30 (lethal dose of radiation anticipated to cause 50% of deaths of the irradiated animal within 30 days) level compared to RI alone [4,7], and, RCI mice die earlier than RI mice.…”

Section: Introductionmentioning

confidence: 99%

“…A pattern that shows 9.5/9.75 Gy RCI delaying the wound closure by one to two weeks compared to SW alone is also commonly observed [4,19]. Multiple studies conducted for MCM screening have demonstrated that leukocyte growth factors, US FDA-approved mitigators for hematopoietic acute radiation syndrome (H-ARS), such as the granulocyte-colony stimulating factor (G-CSF) and PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) [16,[22][23][24], fail to enhance the survival of mice after RCI [16,21], possibly because they further delay wound closure in RCI animals compared to the vehicle treatment [15]. However, other products that have been tested in our RCI mouse model, such as ghrelin [17], ciprofloxacin [10], L-citrulline [21], and bone marrow mesenchymal stem cells (BMSCs) [12], mitigate RCI, at least partially, possibly due to their effects on accelerating wound closure in RCI animals.…”

Section: Introductionmentioning

confidence: 99%

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Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

Wang

Lin

Zhai

et al. 2022

Toxics

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Radiation-combined injury (RCI) augments the risk of morbidity and mortality when compared to radiation injury (RI) alone. No FDA-approved medical countermeasures (MCMs) are available for treating RCI. Previous studies implied that RI and RCI elicit differential mechanisms leading to their detrimental effects. We hypothesize that accelerating wound healing improves the survival of RCI mice. In the current study, we examined the effects of RCI at different doses on lethality, weight loss, wound closure delay, and proinflammatory status, and assessed the relative contribution of systemic and local elements to their delayed wound closure. Our data demonstrated that RCI increased the lethality and weight loss, delayed skin wound closure, and induced a systemic proinflammatory status in a radiation dose-dependent manner. We also demonstrated that delayed wound closure did not specifically depend on the extent of hematopoietic suppression, but was significantly influenced by the toxicity of the radiation-induced systemic inflammation and local elements, including the altered levels of proinflammatory chemokines and factors, and the dysregulated collagen homeostasis in the wounded area. In conclusion, the results from our study indicate a close association between delayed wound healing and the significantly altered pathways in RCI mice. This insightful information may contribute to the evaluation of the prognosis of RCI and development of MCMs for RCI.

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Section: Micementioning

confidence: 99%

Section: Total Body Irradiationmentioning

confidence: 99%

Section: Skin Woundingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

Wang

Lin

Zhai

et al. 2022

Toxics

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Combined radiation injury and its impacts on radiation countermeasures and biodosimetry

Kiang

Blakely

2023

International Journal of Radiation Biology

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Purpose: Preparedness for medical responses to major radiation accidents and the increasing threat of nuclear warfare worldwide necessitates an understanding of the complexity of combined radiation injury (CI) and identifying drugs to treat CI is inevitably critical. The vital sign and survival after CI were presented. The molecular mechanisms, such as microRNA pathways, NF- κ B-iNOS-IL-18 pathway, C3 production, the AKT-MAPK cross-talk, and TLR/MMP increases, underlying CI in relation to organ injury and mortality were analyzed. At present, no FDA-approved drug to protect, mitigate, or treat CI is available. The development of CI-specific medical countermeasures was reviewed. Because of the worsened acute radiation syndrome resulting from CI, diagnostic triage can be problematic. Therefore, biodosimetry and CI are bundled together with the need to establish effective triage methods with CI. Conclusions: CI mouse model studies at AFRRI are reviewed addressing molecular responses, findings from medical countermeasures, and a proposed plasma proteomic biodosimetry approach based on a panel of radiation-responsive biomarkers (i.e., CD27, Flt-3L, GM-CSF, CD45, IL-12, TPO) negligibly influenced by wounding in an algorithm used for dose predictions is described.

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Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation

Sharma,

Kalonia,

Kumar

et al. 2024

International Journal of Radiation Biology

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PEG-G-CSF and L-Citrulline Combination Therapy for Mitigating Skin Wound Combined Radiation Injury in a Mouse Model

Cited by 12 publications

References 42 publications

Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

Combined radiation injury and its impacts on radiation countermeasures and biodosimetry

Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation

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