7 research outputs found
Lipoic acid plays a role in scleroderma: insights obtained from scleroderma dermal fibroblasts
Abstract
Introduction
Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote type I collagen (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as cofactors and antioxidants and are produced by lipoic acid synthetase (LIAS). Our goals in this study were to examine whether LA and LIAS were deficient in SSc patients and to determine the effect of DHLA on the phenotype of SSc dermal fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was included as a comparison.
Methods
Dermal fibroblasts were isolated from healthy subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase (MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor 1 (PAI-1) and LIAS were measured by enzyme-linked immunosorbent assay. The expression of Col I was measured by immunofluorescence, hydroxyproline assay and quantitative PCR. PDGFR phosphorylation and α-smooth muscle actin (αSMA) were measured by Western blotting. Student’s t-tests were performed for statistical analysis, and P-values less than 0.05 with two-tailed analysis were considered statistically significant.
Results
The expression of LA and LIAS in SSc dermal fibroblasts was lower than normal fibroblasts; however, LIAS was significantly higher in SSc plasma and appeared to be released from monocytes. DHLA lowered cellular oxidative stress and decreased PDGFR phosphorylation, Col I, PAI-1 and αSMA expression in SSc dermal fibroblasts. It also restored the activities of phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of MMP-1 and MMP-3, and DHLA increased them. In contrast, TIMP-1 levels were higher in SSc, but DHLA had a minimal effect. Both DHLA and NAC increased MMP-1 activity when SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than NAC in most cases.
Conclusions
DHLA acts not only as an antioxidant but also as an antifibrotic because it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC, LA, or DHLA, could be beneficial for patients with SSc.http://deepblue.lib.umich.edu/bitstream/2027.42/112060/1/13075_2014_Article_411.pd
Effect of alcohol type and amount on the total energy consumption and yield of the free fatty acids esterification reaction with simultaneous adsorptive water removal
<p>The present work investigates the energy consumption and yield of the esterification reaction of free fatty acids (waste oil pretreatment) under a simultaneous water removal by adsorption. The reaction was performed under methanol, ethanol, and 1-propanol at the optimum reaction temperature of 100°C. The higher boiling point temperature of 1-propanol reduced the energy requirement of the reaction by 36.3 and 34.4% compared to methanol and ethanol, respectively. Moreover, despite the higher reactivity associated with alcohols having lower carbon chains, the reaction yield was approximately 16.4% higher under 1-propanol than the other two alcohols. This can be ascribed to the ability to use higher amounts of 1-propanol while maintaining lower energy consumption. The results also indicated that the reaction at 100°C under methanol and ethanol had a similar energy consumption and yield, favoring the use of the renewable ethanol over the widely used nonrenewable methanol. Finally, these findings highlight the importance of investigating the energy consumption of novel oil pretreatment processes and not solely focus on their ability to convert free fatty acids to biofuel.</p