Evaluation of potential ionizing irradiation protectors and mitigators using clonogenic survival of human umbilical cord blood hematopoietic progenitor cells

Goff, Julie P.; Shields, Donna; Wang, Hong; Skoda, Erin M.; Sprachman, Melissa M.; Wipf, Peter; Garapati, Venkata Krishna; Atkinson, Jeffrey; London, Barry; Lazo, John S.; Kagan, Valerian E.; Epperly, Michael W.; Greenberger, Joel S.

doi:10.1016/j.exphem.2013.08.001

Cited by 11 publications

(12 citation statements)

References 25 publications

(67 reference statements)

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“…Minimum toxicity has been detected at the dose of 30 mg/kg (27). IV delivery of JP4-039 in Cremophor/ethanol was compared to the previously published formulation F14 (13,28,31). The results with both Cremphor EL/ETOH and F14 formulations demonstrated effective radiation mitigation at 24 h after 9.25 Gy TBI (data not shown).…”

Section: Comparison Of IV Delivery Of Jp4-039 In Four Formulationsmentioning

confidence: 98%

Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039)

Epperly

Wipf

Fisher

et al. 2018

In Vivo

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Section: Comparison Of IV Delivery Of Jp4-039 In Four Formulationsmentioning

confidence: 98%

Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039)

Epperly

Wipf

Fisher

et al. 2018

In Vivo

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“…Techniques for long-term bone marrow culture, establishment of bone marrow stromal cell lines, and Interleukin 3 (IL-3) dependent hematopoietic progenitor cell lines have been published [ 36 , 77 ]. Methods for growing fresh bone marrow colony forming units CFU-GEMM have been published previously [ 78 ].…”

Section: Methodsmentioning

confidence: 99%

Antioxidant Approaches to Management of Ionizing Irradiation Injury

et al. 2015

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Ionizing irradiation induces acute and chronic injury to tissues and organs. Applications of antioxidant therapies for the management of ionizing irradiation injury fall into three categories: (1) radiation counter measures against total or partial body irradiation; (2) normal tissue protection against acute organ specific ionizing irradiation injury; and (3) prevention of chronic/late radiation tissue and organ injury. The development of antioxidant therapies to ameliorate ionizing irradiation injury began with initial studies on gene therapy using Manganese Superoxide Dismutase (MnSOD) transgene approaches and evolved into applications of small molecule radiation protectors and mitigators. The understanding of the multiple steps in ionizing radiation-induced cellular, tissue, and organ injury, as well as total body effects is required to optimize the use of antioxidant therapies, and to sequence such approaches with targeted therapies for the multiple steps in the irradiation damage response.

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“…JP4-039 enters the matrix and provides radical and electron scavenging activity by virtue of its nitroxide radical containing 4-amino-TEMPO payload [20,21]. Moreover, JP4-039 has demonstrated efficacy as a radiation protector and mitigator in quiescent cells [22], in a mouse model of radiation-induced skin damage by reducing ROS in mitochondria [23], and as radical protector for colony-forming unit-granulocyte-erythroid-megakaryocyte-monocytes [24].…”

Section: Accepted Articlementioning

confidence: 99%

“…FEBS Open Bio (2020) © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. 24 hours (from >20 mins to 24 hours) ("prewashed samples"). In the presence of 5µM JP4-039 from prewashed samples (that lacks the initial burst release), HCAEC demonstrated 25.8% Increase in tube formation (Fig 6B).…”

Section: Accepted Articlementioning

confidence: 99%

Delivery of a mitochondria‐targeted antioxidant from biocompatible, polymeric nanofibrous scaffolds

et al. 2020

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Cardiovascular disease has been associated with increased levels of reactive oxygen species (ROS). Recently, we have shown that a critical balance between cytosolic ROS and mitochondrial ROS is crucial in cardiovascular health and that modulation of mitochondrial ROS helps prevent detrimental effects of cytosolic ROS on endothelial cells (EC) in transgenic animals. Here, we report the development of a controlled delivery system for a mitochondria-targeted antioxidant, JP4-039, from an electrospun scaffold made of FDA-approved biocompatible polymeric nanofibers. We demonstrate that the active antioxidant moiety was preserved in released JP4-039 for over 72 h using electron paramagnetic resonance. We also show that both the initial burst release of the drug within the first 20 min and the ensuing slow and sustained release that occurred over the next 24 h improved tube formation in human coronary artery ECs (HCAEC) in vitro. Taken together, these findings suggest that electrospinning methods can be used to upload mitochondrial antioxidant (JP4-039) onto a biocompatible nanofibrous PLGA scaffold, and the uploaded drug (JP4-039) retains nitroxide antioxidant properties upon release from the scaffold, which in turn can reduce mitochondrial ROS and improve EC function in vitro. Cardiovascular disease, including ischemic heart disease and myocardial infarction (MI), is the leading cause of death in the world. One of the major consequences of MI is death of cardiomyocytes leading to cardiac remodeling, fibrosis, and heart failure [1]. There are major efforts undergoing to improve blood supply to the ischemic myocardium by inducing the growth or sprouting of new blood vessels, that is, angiogenesis, from the existing coronary vessels. Recent work from our laboratory and others showed that reactive oxygen species (ROS) plays a major role in determining coronary vascular endothelial cell (EC) proliferation, migration, and tube formation in vitro [2-5]. ECs have several intracellular sources for ROS, including membrane-bound NADPH oxidases, mitochondria, peroxisome, and cytochrome P450 [6-12]. Whereas the increase in ROS is believed to be harmful for the cardiovascular system, the use of global

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Evaluation of potential ionizing irradiation protectors and mitigators using clonogenic survival of human umbilical cord blood hematopoietic progenitor cells

Cited by 11 publications

References 25 publications

Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039)

Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039)

Antioxidant Approaches to Management of Ionizing Irradiation Injury

Delivery of a mitochondria‐targeted antioxidant from biocompatible, polymeric nanofibrous scaffolds

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