Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig

Giese, Arnaud P. J.; Guarnaschelli, Jess G.; Ward, Jonette A.; Choo, Daniel I.; Riazuddin, Saima; Ahmed, Zubair M.

doi:10.1371/journal.pone.0143606

Cited by 11 publications

(7 citation statements)

References 17 publications

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“…In fact, dosimeters 2, 11 and 15 presented higher doses than dosimeters 12 and 13 due to their position next to the round cut-out. A few studies in literature have developed lead-shielding devices for preclinical assays involving small animals [5,[14][15]. Our results showed that the lead-based body-shielding device was able to attenuate close to 100% on the long axis of the conical tube, indicating a body equivalent dose below 1 Sv.…”

Section: Resultsmentioning

confidence: 69%

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Development of a shielding device for radiotherapy of breast cancer-bearing mice

et al. 2020

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Breast cancer is the fifth most common cause of death worldwide. Currently, one of the standard treatments for breast cancer is radiation therapy (RT). On the other hand, mouse models have been used in pre-clinical studies for breast cancer RT, requiring dedicated shielding to exposure the breast region. In this work, we considered the values of the lead attenuation coefficient and the tenth reducing layer for a 60Co irradiator and developed a lead shielding device for breast cancer-bearing mice to be exposed to localized breast RT. Five-kg of lead were exposed to temperature of 340ºC and inserted into an aluminum mold previously adjusted to the dimensions of the device. After solidification, the device was shaped into a cylinder with dimension of 14 x 15 x 7 cm (height x width x thickness, respectively). A round cut-out for breast exposure of 1 cm in diameter was made at 5 cm from the basis of the device. For shielding device validation, we performed calibrations to establish a dose of 10 Gy in the target. Fifteen CaSO4:Dy thermoluminescent dosimeters were distributed along a 50 mL conical tube to simulate the mouse position inside the shielding. The shielding device was placed at a fixed distance of 10 cm from the target for optimal exposure time. After irradiation, the dosimeters were read on a thermoluminescent reader. According to our results, we were able to develop a body-shielding device that assured the required dose for RT of breast cancer in mice.

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Section: Resultsmentioning

confidence: 69%

“…However, local RT for small animals is not a simple task. Depending on radiation source, a physical barrier is necessary to deliver the dose in the target while sparing healthy tissues [5].…”

Section: Introductionmentioning

confidence: 99%

Development of a shielding device for radiotherapy of breast cancer-bearing mice

et al. 2020

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“…Should PrC-210 follow an entirely different clinical development path, with a clinical indication that has a clear short-term clinical end point, to establish human efficacy, such as suppression of radiotherapy-induced hearing loss (31)? And, once PrC-210 becomes an approved drug for this or another indication, then perhaps over a decade, should we explore PrC-210 as a diagnostic radiation radioprotector.…”

Section: Discussionmentioning

confidence: 99%

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector

et al. 2018

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While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an OH pulse reduced to background theOH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

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“…However, it has a narrow preexposure time window and can only be administered via intravenous injection [ 14 ]. Moreover, it can induce side effects such as vomiting, hypotension, hypocalcemia, and allergic reactions [ 15 , 16 ]. Owing to these drawbacks, the clinical application of amifostine has been significantly limited.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of a Novel Aminothiol Compound as Potential Radioprotector

Wang

Miao

et al. 2021

Oxidative Medicine and Cellular Longevity

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The risk of radiation damage has increased with the rapid development of nuclear technology and radiotherapy. Hence, research on radioprotective agents is of utmost importance. In the present study, a novel aminothiol compound 12, containing a linear alkylamino backbone and three terminal thiols, was synthesized. Owing to the appropriate capped groups in the chains, it has an improved permeability and oral bioavailability compared to other radioprotective agents. Oral administration of compound 12 improved the survival of mice that received lethal doses of γ-irradiation. Experimental results demonstrated that compound 12 not only mitigated total body irradiation-induced hematopoietic injury by increasing the frequencies of hematopoietic stem and progenitor cells but also prevented abdominal irradiation-induced intestinal injury by increasing the survival of Lgr5+ intestinal cells, lysozyme+ Paneth cells, and Ki67+ cells. In addition, compound 12 decreased oxidative stress by upregulating the expression of Nrf2 and NQO1 and downregulating the expression of NOX1. Further, compound 12 inhibited γ-irradiation-induced DNA damage and alleviated G2/M phase arrest. Moreover, compound 12 decreased the levels of p53 and Bax and increased the level of Bcl-2, demonstrating that it may suppress radiation-induced apoptosis via the p53 pathway. These results indicate that compound 12 has the possibility of preventing radiation injury and can be a potential radioprotector for clinical applications.

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Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig

Cited by 11 publications

References 17 publications

Development of a shielding device for radiotherapy of breast cancer-bearing mice

Development of a shielding device for radiotherapy of breast cancer-bearing mice

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector

Design, Synthesis, and Biological Evaluation of a Novel Aminothiol Compound as Potential Radioprotector

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