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Open AccessArticle

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

1
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA
2
Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
3
Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(12), 2525; https://doi.org/10.3390/ijms18122525
Received: 6 November 2017 / Revised: 14 November 2017 / Accepted: 16 November 2017 / Published: 25 November 2017
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung. View Full-Text
Keywords: antioxidant; cell cycle; human lung sections; inflammation; LGM2605; organ culture; oxidative stress; phase II enzymes; proton radiation; reactive oxygen species; senescence antioxidant; cell cycle; human lung sections; inflammation; LGM2605; organ culture; oxidative stress; phase II enzymes; proton radiation; reactive oxygen species; senescence
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Velalopoulou, A.; Chatterjee, S.; Pietrofesa, R.A.; Koziol-White, C.; Panettieri, R.A.; Lin, L.; Tuttle, S.; Berman, A.; Koumenis, C.; Christofidou-Solomidou, M. Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage. Int. J. Mol. Sci. 2017, 18, 2525.

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