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Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice.

Lee SJ, Yi CO, Heo RW, Song DH, Cho YJ, Jeong YY, Kang KM, Roh GS, Lee JD - PLoS ONE (2015)

Bottom Line: Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group.Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA.These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.

ABSTRACT
Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

No MeSH data available.


Related in: MedlinePlus

Effects of clarithromycin on inflammation in irradiated lungs of mice.(A) TNF-α expression in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT + CLA), and clarithromycin only (CLA) animal groups. (B) TNFR1 and TNFR2 expression in lungs of respective groups. (C and D) Acetylated NF-κB p65 and (E) COX-2 expression in lungs of respective groups. Densitometry values were normalized to β-actin and data are presented as mean ± SEM (n = 2–6 mice per group). *p<0.05 vs CTL mice; †p<0.05 vs RT mice. (F) Immunostained COX-2 in lung tissue by group. Scale bar = 100 μm.
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pone.0131671.g002: Effects of clarithromycin on inflammation in irradiated lungs of mice.(A) TNF-α expression in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT + CLA), and clarithromycin only (CLA) animal groups. (B) TNFR1 and TNFR2 expression in lungs of respective groups. (C and D) Acetylated NF-κB p65 and (E) COX-2 expression in lungs of respective groups. Densitometry values were normalized to β-actin and data are presented as mean ± SEM (n = 2–6 mice per group). *p<0.05 vs CTL mice; †p<0.05 vs RT mice. (F) Immunostained COX-2 in lung tissue by group. Scale bar = 100 μm.

Mentions: To investigate the effect of CAL on radiation-induced pro-inflammatory cytokine and its receptors, expression levels of TNF-α, TNFR1, and TNFR2 were measured. We found that the expression levels of TNF-α, TNFR1, and TNFR2 in RT mice lung tissue were elevated compared with corresponding levels in lungs of CTL mice. However, concomitant administration of CLA with thoracic irradiation significantly reduced expression levels of TNF-α, TNFR1, and TNFR2 (Fig 2A and 2B).


Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice.

Lee SJ, Yi CO, Heo RW, Song DH, Cho YJ, Jeong YY, Kang KM, Roh GS, Lee JD - PLoS ONE (2015)

Effects of clarithromycin on inflammation in irradiated lungs of mice.(A) TNF-α expression in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT + CLA), and clarithromycin only (CLA) animal groups. (B) TNFR1 and TNFR2 expression in lungs of respective groups. (C and D) Acetylated NF-κB p65 and (E) COX-2 expression in lungs of respective groups. Densitometry values were normalized to β-actin and data are presented as mean ± SEM (n = 2–6 mice per group). *p<0.05 vs CTL mice; †p<0.05 vs RT mice. (F) Immunostained COX-2 in lung tissue by group. Scale bar = 100 μm.
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Related In: Results  -  Collection

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pone.0131671.g002: Effects of clarithromycin on inflammation in irradiated lungs of mice.(A) TNF-α expression in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT + CLA), and clarithromycin only (CLA) animal groups. (B) TNFR1 and TNFR2 expression in lungs of respective groups. (C and D) Acetylated NF-κB p65 and (E) COX-2 expression in lungs of respective groups. Densitometry values were normalized to β-actin and data are presented as mean ± SEM (n = 2–6 mice per group). *p<0.05 vs CTL mice; †p<0.05 vs RT mice. (F) Immunostained COX-2 in lung tissue by group. Scale bar = 100 μm.
Mentions: To investigate the effect of CAL on radiation-induced pro-inflammatory cytokine and its receptors, expression levels of TNF-α, TNFR1, and TNFR2 were measured. We found that the expression levels of TNF-α, TNFR1, and TNFR2 in RT mice lung tissue were elevated compared with corresponding levels in lungs of CTL mice. However, concomitant administration of CLA with thoracic irradiation significantly reduced expression levels of TNF-α, TNFR1, and TNFR2 (Fig 2A and 2B).

Bottom Line: Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group.Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA.These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.

ABSTRACT
Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

No MeSH data available.


Related in: MedlinePlus