Beneficial effects of N-acetylcysteine on protease-antiprotease balance in attenuating bleomycin-induced pulmonary fibrosis in rats.

Figures

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  Figure 1. Lung histopathology to assess parenchymal inflammation and remodelling along with bronchovascular remodelling after bleomycin instillation and N-acetylcysteine therapy (hematoxylin and eosin stain). Progressive increase in interstitial, peribronchiolar/perivascular inflammation along with increase in fibrosis was observed on day 7, 14 and 28 in bleomycin instilled rats. Normal lung parenchymal architecture and bronchovascular bundles in saline control groups at all time intervals i.e. 7th, 14th and 28th days. Bleomycin-induced parenchymal inflammation and remodelling was significantly reduced on different days in NAC-treated rats

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  Figure 2. Total lung collagen content in bleomycin instilled animals before and after treatment with N-acetylcysteine. ***P<0.001 vs control group; •••P<0.001 vs bleomycin group on 14th day and on 28th day

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  Figure 3. The changes in the mRNA expression of MMP-9 in bleomycin instilled and NAC treated animals. ***P<0.001 vs control group; ••P<0.01 vs bleomycin group on day 28; •••P<0.001 vs bleomycin group on day 28 MMP-9: matrix metalloproteinase-9; NAC: N-acetylcysteine

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  Figure 4. The changes in MMP-9 protein expression in alveolar epithelial cells and macrophages following bleomycin instillation and N-acetylcysteine treatment. MMP-9 is maximally expressed in the inflammatory cells in the interstitium and perivascular region on 14th day. Treatment with NAC attenuated interstitial fibrosis to grade 2 and reduced parenchymal collagen deposition. The MMP-9 protein expression was persistent in the interstitial macrophages, while it was reduced in the perivascular inflammatory cells on 28th day. Treatment with NAC reduced parenchymal collagen deposition The quantification of MMP-9 protein expression in the lung parenchyma of bleomycin instilled and NAC treated animals. ***P<0.001 vs control group; •••P<0.001 vs bleomycin on day 7; ••P<0.01 vs bleomycin on day 14 and 28 (4B)

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  Figure 5. The changes in the Tissue inhibitor of Matrix metalloproteinase-1 (TIMP-1) mRNA expression in bleomycin instilled animals. •••P<0.001 vs bleomycin

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  Figure 6. The changes in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in saline control lungs and after bleomycin instillation in alveolar epithelial cells and bronchial epithelial cells (6A). Quantification of the intensity of TIMP-1 expression in the lung parenchyma. ***P<0.001 vs control, •••P<0.001 and ••P<0.01 vs bleomycin (6B)

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  Figure 7.. Ratio of mean MMP-9/TIMP-1mRNA (7A) and ratio of mean MMP-9/TIMP-1 protein balance (7B) after bleomycin and NAC treatment in male Wistar rat

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  Figure 8. The changes in the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) mRNA levels in the lung after bleomycin instillation and NAC treatment

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  Figure 9. The changes in the TIMP-3 protein expression in saline control lungs and after bleomycin instillation (N=6 in each group) in wistar rat (9A). Quantification of the intensity of TIMP-3 expression in saline control lungs and after bleomycin instillation. ***P<0.001 vs control, •••P<0.001, ••P<0.01 vs bleomycin (9B)

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  Figure 10. Ratio of mean MMP-9/TIMP-3mRNA (Figure 10A) and ratio of mean MMP-9/TIMP-3 protein balance (10B) after bleomycin and NAC treatment in wistar rat

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  Figure 11. The changes in TGF-β1 mRNA levels ***P<0.001 vs normal control in wistar rat; •••P<0.001, •P<0.05 vs bleomycin. (11A) and active TGF-β1 protein levels after bleomycin and NAC treatment ••P<0.01 vs bleomycin, ***P<0.001 vs normal control, •••P<0.001 vs bleomycin (11B)

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  Figure 12. Changes in the transforming Growth factor-β1 (TGF-β1) protein expression in saline control lungs and after bleomycin instillation in wistar rat (12A). Quantification of the intensity of TGF-β1 protein expression in the lung parenchyma. ***P<0.001 vs control, •••P<0.001 vs bleomycin (12B)