Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis

Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug...

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Bibliographic Details
Published in:Molecular medicine (Cambridge, Mass.) Vol. 25; no. 1; p. 27
Main Authors: Rodriguez, L R, Bui, S N, Beuschel, R T, Ellis, E, Liberti, E M, Chhina, M K, Cannon, B, Lemma, M, Nathan, S D, Grant, G M
Format: Journal Article
Language:English
Published: England BioMed Central 13-06-2019
BMC
Subjects:
Apoptosis
Clinical trials
Curcumin
FDA approval
Fibroblasts
Gene expression
Growth factors
Hospitals
Lung diseases
Lungs
N-acetylcysteine
Older people
Oxidative stress
Pathogenesis
Population
Pulmonary fibrosis
United States > US
Curcumin
Pulmonary fibrosis
N-acetylcysteine
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Summary:Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells. Primary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species. We demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential. These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.
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ISSN:1076-1551
1528-3658
DOI:10.1186/s10020-019-0096-z