Korean J Physiol Pharmacol.  2013 Aug;17(4):267-274. 10.4196/kjpp.2013.17.4.267.

Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

• Cho YJ
• Yi CO
• Jeon BT
• Jeong YY
• Kang GM
• Lee JE
• Roh GS
• Lee JD

• KMID: 2285460
• DOI: http://doi.org/10.4196/kjpp.2013.17.4.267

Abstract

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-alpha (TNF-alpha), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappaB) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Keyword

Curcumin; Fibrosis; Inflammation; Lung; Radiation

MeSH Terms

Animals
Blotting, Western
Collagen
Connective Tissue Growth Factor
Curcumin
Cyclooxygenase 2
Edema
Fibrosis
Inflammation
Lung
Lung Injury
Macrophages
Pneumonia
Rats
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha
Collagen
Connective Tissue Growth Factor
Curcumin
Cyclooxygenase 2
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Effects of curcumin on alveolar inflammation in radiation-induced rat lung. (A) Representative photomicrographs of H & E-stained lung sections from control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. Scale bar=200 µm. (B) Representative photomicrographs of immunostained F4/80 in rat lungs from each group. Scale bar=100 µm. Arrows indicate macrophage.

• 

  Fig. 2 Effects of curcumin on alveolar septal thickening and fibrosis in radiation-induced rat lungs. (A) Representative photomicrographs of H & E-stained lung sections from control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. Scale bar=100 µm. (B) Alveolar septal thickness is presented as mean±SEM. (C) Representative photomicrographs of Masson's trichrome-stained lung sections from each group. Scale bar=200 µm. (D) Collagen content measured by Sircol assay in rat lungs (n=5~6 per group) after radiation. p<0.05 by ANOVA. *p<0.05, †p<0.001 vs. CTL and RT, respectively.

• 

  Fig. 3 Effects of curcumin on serum TGF-β1 and lung TGF-β1 and CTGF expression in irradiated rats. (A) Serum concentrations (n=5~6 per group) of TGF-β1 in control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. (B) Western blot showing TGF-β1 and CTGF in lung from each group. (C) Quantification of lung TGF-β1 from western blot analysis. Densitometry values of each protein were normalized to α-tubulin and represented as arbitrary units (A.U.) relative to CTL levels. Data (n=5~6 per group) are presented as mean±SEM. *p<0.05 vs. CTL rats; †p<0.05 vs. RT rats.

• 

  Fig. 4 Effects of curcumin on TNF-α, TNFR1, and TNFR2 expression in irradiated rat lung. (A) Western blot showing TNF-α, TNFR1, and TNFR2 in lungs from control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. (B) Western blot quantification of lung TNF-α and TNFR1. TNFR2 expression was unchanged in all groups. Densitometry values of each protein were normalized to α-tubulin and represented as arbitrary units (A.U.) relative to CTL expression levels. Data (n=5~6 per group) are presented as mean±SEM. *p<0.05 vs. CTL rats; †p<0.05 vs. RT rats.

• 

  Fig. 5 Effects of curcumin on NF-κB p65 nuclear translocation in irradiated rat lung. (A) Western blot showing NF-κB p65 in the cytoplasm and nucleus of lungs from control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. Cytosolic (cyto) and nuclear (nu) protein levels were normalized to β-actin and lamin A, respectively. (B) Representative photomicrographs of immunostained NF-κB p65 in lung from each group. Scale bar=100 µm. Arrows indicate macrophage. (C) Western blot showing acetylated NF-κB p65 in lungs from each group. Densitometry values for acetylated NF-κB p65 were normalized to α-tubulin and expressed as arbitrary units. Data (n=5~6 per group) are presented as mean±SEM. *p<0.05 vs. CTL rats; †p<0.05 vs. RT rats.

• 

  Fig. 6 Effects of curcumin on COX-2 expression in irradiated rat lung. (A) Western blot showing COX-2 in lungs from control (CTL), radiation (RT), radiation+curcumin (RT+Cur), and curcumin (Cur) rats. (B) Western blot quantification of lung COX-2. Densitometry values of each protein were normalized to α-tubulin and represented as arbitrary units relative to CTL. Data (n=5~6 per group) are presented as mean±SEM. *p<0.05 vs. CTL rats; †p<0.05 vs. RT rats. (C) Representative micrographs of immunostained COX-2 in lungs from each group. Scale bar=100 µm.

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