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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

[Is the decrease in corneal endothelial cell density in relation to age linear?]. / Ist die Abnahme der Hornhaut-Endothelzellzahl mit dem Alter wirklich linear?

BACKGROUND: Corneal endothelial cell density is an important factor in maintaining corneal transparency. It is generally assumed that corneal endothelial cell density continuously decreases from birth. MATERIAL AND METHODS: On healthy eyes of 191 subjects, images of the endothelium were taken using a specular endothelial microscope. Statistical analyses were done on corneal endothelial cell density, polymegatism and proportion of hexagonal cells in relation to age. RESULTS: Extrapolated endothelial cell density at birth was 2957 cells/mm2. Using linear regression, the calculated annual cell loss was 7.58 cells/mm2. With age, polymegatism is increasing and the proportion of hexagonal cells is decreasing. Based on our data, the decrease in corneal endothelial cell density can be described in two different time periods: from birth until 35 years of age, endothelial cell density is considerably and continuously decreasing; after this corneal endothelial cell density is decreasing at a much slower rate. CONCLUSIONS: Our data suggest that changes in the structure of the corneal endothelium are different in the first three decades of life compared to later decades. Reasons for this could be mechanical and physical influences, changing biochemical properties of the cornea and aqueous humor, or the embryological origin of the endothelium. This observation shows that age generally is not a deciding factor for intraocular surgeries.