Dehydroxymethylepoxyquinomicin Inhibits Expression and Production of Inflammatory Mediators in Interleukin-1β β β β β-induced Human Chondrocytes

The present research was carried out to determine the effects of a nuclear factor-kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), derivative of the antibiotic epoxyquinomicin C, on normal human chondrocytes treated with interleukin-1beta (IL-1beta). This is a cell model particularly useful to reproduce the mechanisms involved in degenerative arthropathies, where oxidative-inflammatory stress determines a progressive destruction of the articular cartilaginous tissue. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inter-cellular adhesion molecule (ICAM)-1 was evaluated through Western blot analysis. The release of chemokines like monocyte chemoattractant protein-1 (MCP-1), regulated upon normal activation T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) were determined by ELISA assays. DHMEQ acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of nitrite in human chondrocytes. In addition, DHMEQ induces a significant dose-dependent decrease in ICAM expression, MCP-1, RANTES, and IL-8 release. DHMEQ helps to decrease the expression and production of pro-inflammatory mediators in IL-1beta-induced chondrocytes. DHMEQ may become a therapeutic agent for treatment of chondro-degenerative diseases

Source patterns of potentially toxic elements (PTEs) and mining activity contamination level in soils of Taltal city (northern Chile)

Mining activities are among the main sources of potentially toxic elements (PTEs) in the environment which constitute a real concern worldwide, especially in developing countries. These activities have been carried out for more than a century in Chile, South America, where, as evidence of incorrect waste disposal practices, several abandoned mining waste deposits were left behind. This study aimed to understand multi-elements geochemistry, source patterns and mobility of PTEs in soils of the Taltal urban area (northern Chile). Topsoil samples (n = 125) were collected in the urban area of Taltal city (6 km2) where physicochemical properties (redox potential, electric conductivity and pH) as well as chemical concentrations for 35 elements were determined by inductively coupled plasma optical emission spectrometer. Data were treated following a robust workflow, which included factor analysis (based on ilr-transformed data), a new robust compositional contamination index (RCCI), and fractal/multi-fractal interpolation in GIS environment. This approach allowed to generate significant elemental associations, identifying pool of elements related either to the geological background, pedogenic processes accompanying soil formation or to anthropogenic activities. In particular, the study eventually focused on a pool of 6 PTEs (As, Cd, Cr, Cu, Pb, and Zn), their spatial distribution in the Taltal city, and the potential sources and mechanisms controlling their concentrations. Results showed generally low baseline values of PTEs in most sites of the surveyed area. On a smaller number of sites, however, higher values concentrations of As, Cd, Cu, Zn and Pb were found. These corresponded to very high RCCI contamination level and were correlated to potential anthropogenic sources, such as the abandoned mining waste deposits in the north-eastern part of the Taltal city. This study highlighted new and significant insight on the contamination levels of Taltal city, and its links with anthropogenic activities. Further research is considered to be crucial to extend this assessment to the entire region. This would provide a comprehensive overview and vital information for the development of intervention limits and guide environmental legislation for these pollutants in Chilean soils

Natural Antioxidant Polyphenols On Inflammation Management: Anti-glycation Activity Vs Metalloproteinases Inhibition.

The diet polyphenols are a secondary metabolites of plants able to act on inflammation process. Their anti-inflammatory activity is articulated through several mechanisms that are related to their antioxidative and radical scavengers properties. Our work is focused on a novel approach to inflammatory disease management, based on anti-glycative and matrix metalloproteinases (MMPs) inhibition effects, as a connected phenomena. To better understand these correlation, polyphenols Structure-Activity Relationship (SAR) studies were also reported. The antioxidant polyphenols inhibit the AGEs at different levels of the glycation process in the following ways: 1) prevention of Amadori adduct oxidation; 2) trapping reactive dycarbonyl compounds; 3) attenuation of receptor for AGEs (RAGE) expression. Moreover, several flavonoids with radical scavenging property showed also MMPs inhibition interact directly with MMPs or indirectly via radical scavengers and AGEs reduction. The essential polyphenols features involved in these mechanisms are C2-C3 double bond and number and position of hydroxyl, glycosyl and O-methyl groups. These factors induce a change in molecular planarity interfering with the hydrogen bond formation, electron delocalization and metal ion chelation. In particular, C2-C3 double bond improve the antioxidant and MMPs inhibition, while the hydroxylation, glycosylation and methylation induce a positive and negative correlation respectively

Toxicity and Carcinogenicity Mechanisms of Fibrous Antigorite

We studied the effects of fibrous antigorite on mesothelial MeT-5A and monocyte-macrophage J774 cell lines to further understand cellular mechanisms induced by asbestos fibers leading to lung damage and cancer. Antigorite is a mineral with asbestiform properties, which tends to associate with chrysotile or tremolite, and frequently occurs as the predominant mineral in the veins of several serpentinite rocks found abundantly in the Western Alps. Particles containing antigorite are more abundant in the breathing air of this region than those typically found in urban ambient air. Exposure of MeT-5A and J774 cells to fibrous antigorite at concentrations of 5-100 μg/ml for 72 hr induced dose-dependent cytotoxicity. Antigorite also stimulated the ROS production, induced the generation of nitrite and PGE2. MeT-5A cells were more sensitive to antigorite than J774 cells. The results of this study revealed that the fibrous antigorite stimulates cyclooxygenase and formation of hydroxyl and nitric oxide radicals. These changes represent early cellular responses to antigorite fibers, which lead to a host of pathological and neoplastic conditions because free radicals and PGE2 play important roles as mediators of tumor pathogenesis. Understanding the mechanisms of the cellular responses to antigorite and other asbestos particles should be helpful in designing rational prevention and treatment approaches

2-Benzisothiazolylimino-5-benzylidene-4-thiazolidinones as protective agents against cartilage destruction

We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs) 3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protective agents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulated by IL-1β. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs, was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover, selected derivatives 1h and 1g was studied for nuclear factor kappaB (NF-κB) inhibition by Western Blot analysis and for MMP-3 protein release using ELISA test. The structure-activity relationship of tested compounds demonstrates a favorable effect of the para substitution on the 5-benzilydene ring. Compound 1g shows a potent and selective activity on MMP-3 versus MMP-13. Accordingly, 1g possesses high antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production of MMPs and NF-κB expression. Thus 1g can be considered as new potential chondroprotective agent

Natural Flavones and Flavonols: Relationships among Antioxidant Activity, Glycation, and Metalloproteinase Inhibition

Reactive oxygen and nitrogen species as well as advanced glycation endproducts (AGEs) and metalloproteinases (MMPs) play a key role in the development and progression of degenerative processes of body tissues, including skin. Natural antioxidant flavonoids could be beneficial in inhibiting AGEs’ formation and MMPs’ expression. In this study, the antioxidant activity of flavones (luteolin, apigenin, and chrysin) and flavonols (mirycetin, quercetin, and kaempferol) was compared with their inhibitory effects on both metalloproteinases’ (MMP-1, MMP-2, MMP-9, MMP-13) and AGEs’ formation. Comparisons were performed taking into account the hydroxyl group arrangement and the physico-chemical parameters the binding dissociation enthalpy (BDE), ionization potential (IP), partition coefficient (log P), and topological polar surface area (TPSA). Increasing the number of hydroxyl groups led to a proportional enhancement of antioxidant activity while an inverse relationship was observed plotting the antioxidant activity vs. BDE and IP values. All flavonoids acted as AGEs, MMP-1, and MMP-13 inhibitors, but they were less effective against MMP-2 and MMP-9. The inhibition of MMP-1 seemed to be related to the TPSA values while high TPSA and low log P values seemed important conditions for inhibiting MMP-13. Overall, our data suggest that an estimation of flavonoid activity could be anticipated based on their physico-chemical parameters

Dynamic Olfactometry: evaluation of odour intensity and stability of Citronella Oil loaded Solid Lipid Nanoparticles

The Dynamic Olfactometry is a satisfactory method to determine objectively the odour concentration of volatile samples, using a human selected panel. The essential oils (EOs) are composed by lipophilic and highly volatile secondary plant metabolites, including terpenoids, phenol-derived aromatic and aliphatic components. The terpenoids are volatile organic compounds (VOCs) that undergo to oxidative and isomerizzation processes due to the air, light, moisture and high temperatures. Moreover, as a consequence of the high vapour tension of VOCs, the efficacy of EOs are very limited in the time. The Citronella Oil (C.O.) is used extensively as a source of perfumery chemicals or repellent substances, as citronellolal, citronellol and geraniol, that are responsible to their instability. The nanoencapsulation in drug delivery systems represents an efficient strategy to improve the stability and efficacy of EOs-based formulations. In this work the C.O. is formulated in solid lipid nanoparticles (SLNs), by ultrasonication method. The mean diameter (MD), polidispersity index (PDI) and zeta potential (PZ) of C.O. loaded SLN are determined immediately and after one month from production, showing a good long term stability. The aim of the work is the evaluation of odour concentration of C.O. free and loaded in SLN, in order to understand how the formulation can influence volatility, stability and release in SLN formulation. The Dynamic Olfactometry is performed, according to the regulation UNI EN 13725:2004. The results are expressed in OUE/m3 (European Odour Unit, OUE for m3), that represents the amount of odorant, evaporated in 1 m3 of neutral gas, inducing a physiological response, equal to a reference gas used, n-butanol, on a panel. The figure 1 and 2 showed the relationship between the odour intensity (OUE/m3) of the free oil and loaded in SLN, at 2.5% and 0.25%, respectively. The odour intensity is followed for 96 hours. After 24 hours, the odour intensity of free oil is not perceptible at both concentrations used. On the contrary, the odour intensity of C.O. loaded in SLN at 96 hours is 580 OUE/m3, at 2.5%, and 250 OUE/m3, at 0.25%. The obtained results for C.O. loaded in SLN at 2.5% and 0.25%, confirmed a prolonged and concentration-dependent effect of C.O. formulations