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Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.
Bronova, Irina; Smith, Brett; Aydogan, Bulent; Weichselbaum, Ralph R; Vemuri, Kiran; Erdelyi, Katalin; Makriyannis, Alex; Pacher, Pal; Berdyshev, Evgeny V.
Afiliação
  • Bronova I; 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.
  • Smith B; Departments of 2 Radiation Oncology and.
  • Aydogan B; Departments of 2 Radiation Oncology and.
  • Weichselbaum RR; 3 Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
  • Vemuri K; 4 Center for Drug Discovery and.
  • Erdelyi K; 5 Laboratory of Physiological Studies, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; and.
  • Makriyannis A; 6 Center for Drug Discovery, Departments of Pharmaceutical Sciences and Chemistry & Chemical Biology, Northeastern University, Boston, Massachusetts.
  • Pacher P; 4 Center for Drug Discovery and.
  • Berdyshev EV; 1 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and.
Am J Respir Cell Mol Biol ; 53(4): 555-62, 2015 Oct.
Article em En | MEDLINE | ID: mdl-26426981
Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis. Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg intraperitoneally three times per week. Animal survival and parameters of pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy) was associated with marked pulmonary inflammation and fibrosis in mice and high mortality within 15 to 18 weeks after exposure. Genetic deletion or pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and increased animal survival. Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Pirazóis / Lesões Experimentais por Radiação / Protetores contra Radiação / Morfolinas / Receptor CB1 de Canabinoide Limite: Animals Idioma: En Revista: Am J Respir Cell Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Pirazóis / Lesões Experimentais por Radiação / Protetores contra Radiação / Morfolinas / Receptor CB1 de Canabinoide Limite: Animals Idioma: En Revista: Am J Respir Cell Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2015 Tipo de documento: Article