scholarly journals ANTIFIBROTIC ACTIVITY OF MESNA AGAINST AMIODARONE-ASSOCIATED LUNG INJURY IN WISTAR RATS

2019 ◽  
Vol 12 (1) ◽  
pp. 491
Author(s):  
Bahir Abdul Razzaq Mshimesh
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Wistar Rats ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Protective Agent ◽  
Matrix Metalloproteinase 7 ◽  
Smad3 Protein

Objective: Lung fibrosis is a progressive respiratory disease with a high percentage of mortality. Till now, it had bad prognosis to conventional medications. This study was designed to evaluate the role of mesna, the well-known antioxidant agent, against pulmonary fibrosis.Methods: Pulmonary fibrosis was induced by administration of amiodarone to Wistar rats. Lung indices, leukocytes count, oxidative stress markers, cytokines levels, and hydroxyproline contents, in addition to the histopathological tests, were done for control, amiodarone, and mesna plus amiodarone group.Results: The elevated ratio of lung/body weight and total leukocytes count within bronchoalveolar lavage fluid for amiodarone rats was decline significantly when cotreated with mesna therapy. Furthermore, mesna significantly brought down the lipid peroxidation of amiodarone in lung tissue, represented by decreasing malondialdehyde level and increasing superoxide dismutase (SOD) and catalase activity. In addition, mesna diminished the profibrotic transforming growth factor-β1 level while elevated the antifibrotic interferon-γ level, and the high activity of the enzyme matrix metalloproteinase-7 was restored within mesna group. Meanwhile, mesna counteracts the increment of hydroxyproline contents and Ashcroft grading scale within amiodarone group. Histologically, critical improvement in the inflammatory cell penetration and alveolar septa was seen in the lung tissue of rats within mesna group, contrasted with those received just amiodarone. Trichome staining clarified that collagen deposition was notably diminished in the peri-alveolar and peri-bronchial area within mesna group. Moreover, mesna therapy downregulated SMAD3 protein level, which was overexpressed by amiodarone challenge.Conclusion: This study gives evidence that mesna therapy may act as a protective agent against amiodarone-mediated pulmonary fibrosis.

scholarly journals ANTIFIBROTIC ACTIVITY OF MESNA AGAINST AMIODARONE-ASSOCIATED LUNG INJURY IN WISTAR RATS

2019 ◽  
Vol 12 (1) ◽  
pp. 491
Author(s):  
Bahir Abdul Razzaq Mshimesh
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Wistar Rats ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Protective Agent ◽  
Matrix Metalloproteinase 7 ◽  
Smad3 Protein

Objective: Lung fibrosis is a progressive respiratory disease with a high percentage of mortality. Till now, it had bad prognosis to conventional medications. This study was designed to evaluate the role of mesna, the well-known antioxidant agent, against pulmonary fibrosis.Methods: Pulmonary fibrosis was induced by administration of amiodarone to Wistar rats. Lung indices, leukocytes count, oxidative stress markers, cytokines levels, and hydroxyproline contents, in addition to the histopathological tests, were done for control, amiodarone, and mesna plus amiodarone group.Results: The elevated ratio of lung/body weight and total leukocytes count within bronchoalveolar lavage fluid for amiodarone rats was decline significantly when cotreated with mesna therapy. Furthermore, mesna significantly brought down the lipid peroxidation of amiodarone in lung tissue, represented by decreasing malondialdehyde level and increasing superoxide dismutase (SOD) and catalase activity. In addition, mesna diminished the profibrotic transforming growth factor-β1 level while elevated the antifibrotic interferon-γ level, and the high activity of the enzyme matrix metalloproteinase-7 was restored within mesna group. Meanwhile, mesna counteracts the increment of hydroxyproline contents and Ashcroft grading scale within amiodarone group. Histologically, critical improvement in the inflammatory cell penetration and alveolar septa was seen in the lung tissue of rats within mesna group, contrasted with those received just amiodarone. Trichome staining clarified that collagen deposition was notably diminished in the peri-alveolar and peri-bronchial area within mesna group. Moreover, mesna therapy downregulated SMAD3 protein level, which was overexpressed by amiodarone challenge.Conclusion: This study gives evidence that mesna therapy may act as a protective agent against amiodarone-mediated pulmonary fibrosis.

scholarly journals Attenuated pulmonary fibrosis in sialidase-3 knockout (Neu3−/−) mice

2020 ◽  
Vol 318 (1) ◽  
pp. L165-L179 ◽  
Author(s):  
Tejas R. Karhadkar ◽  
Wensheng Chen ◽  
Richard H. Gomer
Keyword(s):  
Pulmonary Fibrosis ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Human Peripheral Blood ◽  
Lavage Fluid ◽  
Scar Tissue ◽  
Transforming Growth Factor Β1 ◽  
Peripheral Blood Mononuclear ◽  
Male And Female

Pulmonary fibrosis involves the formation of inappropriate scar tissue in the lungs, but what drives fibrosis is unclear. Sialidases (also called neuraminidases) cleave terminal sialic acids from glycoconjugates. In humans and mice, pulmonary fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. Of the four mammalian sialidases, we previously detected only NEU3 in the bronchoalveolar lavage fluid from mice with bleomycin-induced pulmonary fibrosis. In this report, we show that NEU3 upregulates extracellular accumulation of the profibrotic cytokines IL-6 and IL-1β, and IL-6 upregulates NEU3 in human peripheral blood mononuclear cells, suggesting that NEU3 may be part of a positive feedback loop potentiating fibrosis. To further elucidate the role of NEU3 in fibrosis, we used bleomycin to induce lung fibrosis in wild-type C57BL/6 and Neu3−/− mice. At 21 days after bleomycin, compared with male and female C57BL/6 mice, male and female Neu3−/− mice had significantly less inflammation, less upregulation of other sialidases and the profibrotic cytokine active transforming growth factor β1, and less fibrosis in the lungs. Our results suggest that NEU3 participates in fibrosis and that NEU3 could be a target to develop treatments for fibrosis.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing

2020 ◽  
Vol 34 ◽  
pp. 205873842092391 ◽  
Author(s):  
Min-na Dong ◽  
Yun Xiao ◽  
Yun-fei Li ◽  
Dong-mei Wang ◽  
Ya-ping Qu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Treatment Group ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Tissue Growth ◽  
Control Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tgf Β1

Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.

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