التفاصيل البيبلوغرافية
| العنوان: |
Cannabidiol (CBD) Protects Lung Endothelial Cells from Irradiation-Induced Oxidative Stress and Inflammation In Vitro and In Vivo. |
| المؤلفون: |
Bauer, Lisa, Alkotub, Bayan, Ballmann, Markus, Hasanzadeh Kafshgari, Morteza, Rammes, Gerhard, Multhoff, Gabriele |
| المصدر: |
Cancers; Nov2024, Vol. 16 Issue 21, p3589, 24p |
| مصطلحات موضوعية: |
CANNABIDIOL, BIOLOGICAL models, IN vitro studies, OXYGENASES, RADIOTHERAPY, BLOOD vessels, APOPTOSIS, BODY weight, OXIDATIVE stress, LUNGS, IN vivo studies, TREATMENT effectiveness, TUMOR markers, MICE, CELL lines, ENDOTHELIAL cells, CHEST tumors, ANIMAL experimentation, DNA damage, INFLAMMATION |
| مستخلص: |
Simple Summary: Radiotherapy remains a central pillar in the therapy of solid tumors, including lung cancer. However, the clinically applied radiation dose to a lung tumor is limited by the radiation-sensitivity of the surrounding normal tissue such as the lungs and heart. Ionizing irradiation causes reactive oxygen species (ROS)-induced chronic vascular inflammation, which can result in fatal irradiation-induced lung diseases such as pneumonitis and fibrosis. In this study, we demonstrate that cannabidiol (CBD), the non-psychogenic component of cannabis, mediates anti-inflammatory and anti-oxidative effects that protect the microvasculature of the lung against radiation-induced damage using in vitro and in vivo murine models. CBD therefore has the potential to improve the clinical outcome of radiotherapy by reducing normal tissue toxicity in the lung. Objective: Radiotherapy, which is commonly used for the local control of thoracic cancers, also induces chronic inflammatory responses in the microvasculature of surrounding normal tissues such as the lung and heart that contribute to fatal radiation-induced lung diseases (RILDs) such as pneumonitis and fibrosis. In this study, we investigated the potential of cannabidiol (CBD) to attenuate the irradiation damage to the vasculature. Methods: We investigated the ability of CBD to protect a murine endothelial cell (EC) line (H5V) and primary lung ECs isolated from C57BL/6 mice from irradiation-induced damage in vitro and lung ECs (luECs) in vivo, by measuring the induction of oxidative stress, DNA damage, apoptosis (in vitro), and induction of inflammatory and pro-angiogenic markers (in vivo). Results: We demonstrated that a non-lethal dose of CBD reduces the irradiation-induced oxidative stress and early apoptosis of lung ECs by upregulating the expression of the cytoprotective mediator heme-oxygenase-1 (HO-1). The radiation-induced increased expression of inflammatory (ICAM-2, MCAM) and pro-angiogenic (VE-cadherin, Endoglin) markers was significantly reduced by a continuous daily treatment of C57BL/6 mice with CBD (i.p. 20 mg/kg body weight), 2 weeks before and 2 weeks after a partial irradiation of the lung (less than 20% of the lung volume) with 16 Gy. Conclusions: CBD has the potential to improve the clinical outcome of radiotherapy by reducing toxic side effects on the microvasculature of the lung. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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