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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 Nrf2 and HO-1 expression levels and on HO-1 immunoreactivity in irradiated lungs of mice.(A) Nrf2 and HO-1 expression levels in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT+CLA), and clarithromycin only (CLA) animal 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. (B) Immunostained HO-1 in lung tissue by group. Scale bar = 100 μm.
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pone.0131671.g004: Effects of clarithromycin on Nrf2 and HO-1 expression levels and on HO-1 immunoreactivity in irradiated lungs of mice.(A) Nrf2 and HO-1 expression levels in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT+CLA), and clarithromycin only (CLA) animal 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. (B) Immunostained HO-1 in lung tissue by group. Scale bar = 100 μm.

Mentions: To evaluate the defense pathway of Nrf/HO-1 in irradiated lungs and its inhibition by CLA, western blot analyses using antibodies to Nrf2 and HO-1 were performed. The expression levels of Nrf2 and HO-1 in lungs of RT mice (vs CTL mice) were elevated. Significant reductions in Nrf2 and HO-1 expression levels were achieved with CLA administration (Fig 4A), and immunohistochemistry confirmed that increased post-irradiation immunoreactivity of HO-1 was inhibited by CLA (Fig 4B). As shown in Fig 4A, histological analysis showed that the percentage of mean intensity of HO-1 in RT mice was 362.61 ± 17.31. However, the percentage in RT+CLA mice (261.26 ± 10.20) was significantly reduced compared to RT mice (p < 0.05).


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 Nrf2 and HO-1 expression levels and on HO-1 immunoreactivity in irradiated lungs of mice.(A) Nrf2 and HO-1 expression levels in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT+CLA), and clarithromycin only (CLA) animal 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. (B) Immunostained HO-1 in lung tissue by group. Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482753&req=5

pone.0131671.g004: Effects of clarithromycin on Nrf2 and HO-1 expression levels and on HO-1 immunoreactivity in irradiated lungs of mice.(A) Nrf2 and HO-1 expression levels in lungs of control (CTL), radiation only (RT), radiation + clarithromycin (RT+CLA), and clarithromycin only (CLA) animal 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. (B) Immunostained HO-1 in lung tissue by group. Scale bar = 100 μm.
Mentions: To evaluate the defense pathway of Nrf/HO-1 in irradiated lungs and its inhibition by CLA, western blot analyses using antibodies to Nrf2 and HO-1 were performed. The expression levels of Nrf2 and HO-1 in lungs of RT mice (vs CTL mice) were elevated. Significant reductions in Nrf2 and HO-1 expression levels were achieved with CLA administration (Fig 4A), and immunohistochemistry confirmed that increased post-irradiation immunoreactivity of HO-1 was inhibited by CLA (Fig 4B). As shown in Fig 4A, histological analysis showed that the percentage of mean intensity of HO-1 in RT mice was 362.61 ± 17.31. However, the percentage in RT+CLA mice (261.26 ± 10.20) was significantly reduced compared to RT mice (p < 0.05).

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