Double aspect of manufactured nanoparticles on oxidative and inflammatory metabolisms : deleterious effects and protective effects

On étudie les effets des nanoparticules (d'argent et de silice) manufacturées sur les métabolismes oxydatifs et inflammatoire. La première partie étudie la toxicité in vivo de l'ingestion de nanoparticules d'argent, pendant 11 semaines, sur un modèle animal - rat Sprague Dawley. Nous y avons mis en évidence l'action toxique des nanoparticules d'argent notamment une hausse de la production d'anion superoxyde par les NADPH oxydases hépatiques et cardiaques, des dyslipidémies, une cytolyse hépatique, une augmentation de cytokines pro-inflammatoires et une tendance à la baisse de l'activité d'enzymes antioxydantes. Ceci nous a conduit à aborder l'étude in vitro, sur des modèles cellulaires intestinaux (Caco-2) et cutanés (HaCaT). Au cours de cette étude, des nanoparticules de silice, fonctionnalisées ou non avec des antioxydants, ont été incubées pendant 24 H en présence des cellules. Nous montrons que la modification de la surface des nanoparticules réduit considérablement leur toxicité en limitant la production d'espèces radicalaires et la mortalité cellulaire. D’autre part, le couplage avec un antioxydant permet d’augmenter la stimulation de voie de signalisation du facteur Nrf2. Cette voie est impliquée dans la protection de l’organisme contre les troubles liés aux espèces radicalaires. En somme, ce travail met en avant les potentialités de la vectorisation d’antioxydants avec des nanoparticules à des fins thérapeutiques.The purpose of this study is to explore the effects of nanoparticles (silver and silica) manufactured on oxidative and inflammatory metabolism. In the first part of this work, we explored the in vivo toxicity from ingestion of silver nanoparticles, for 11 weeks, in an animal model - Sprague Dawley rat. This enabled us to demonstrate the toxic properties of silver nanoparticles including superoxide anion production by hepatic and cardiac NADPH oxidases, dyslipidemia, hepatic cytolysis, an increase in proinflammatory cytokines and a downward trend the activity of antioxidant enzymes. This led us to address the in vitro study on intestinal cell models (Caco-2) and cutaneous (HaCaT). During this study, silica nanoparticles, functionalized or not with anti-oxidants, were incubated for 24 hours in the presence of the cells. We show that the modification of the surface of the nanoparticles significantly reduces their toxicity limiting the production of free radical species and cell death. Furthermore, the coupling with an anti-oxidant increases the stimulation of Nrf2 factor that involves the protection of the body against disorders associated with radical species. In summary, this work highlights the potential of vectorization of antioxidants with nanoparticles for therapeutic purposes

PAOT-Liquid® Technology: An easy Electrochemical Method for Evaluating Antioxidant Capacity of Wines

Polyphenol compounds present in high quantity in wines are well-known to have potent cardio-protective properties through several biological mechanisms including antioxidant activity [1]. A large number of methods have been developed in the laboratory for evaluating this last mechanism in food matrices. Most of them have, however, the disadvantage of being time consuming and require specific analytical protocols and devices. In the present study, we present the electrochemical PAOT (Pouvoir Antioxydant Total)-Liquid® Technology which can be easily used by winemakers for evaluating antioxidant activity during the wine process. The methodology is based on the measurement of electric potential variation resulting from chemical reactions between wine polyphenols and a free radical mediator M• as source of oxidants. Total antioxidant activity as estimated by the PAOT-Liquid® activity was 6.8 fold higher in red wines (n = 14) when compared to rosé (n = 3) and white (n = 3) wines built in a commercial market. Moreover, PAOT-Liquid® activity was highly correlated with total polyphenols content (TPC) of all wines (r = 0.9540, p < 0.0001) and the classical DPPH (2,2-diphenyl-1-picryhydrazyl) assay very which is often used for evaluating antioxidant capacity of food matrices (r = 0.9102, p < 0.0001)

Mitochondrial-targeted antioxidant MitoQ ameliorated metabolic syndrome features much better than Apocynin and Allopurinol in obesogenic diet-fed rats

Mitochondrial-targeted antioxidant MitoQ ameliorated metabolic syndrome features much better than Apocynin and Allopurinol in obesogenic diet-fed rats. Assises du Département Alim

The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome features in obesogenic diet-fed rats better than Apocynin or Allopurinol

The prevalence of metabolic syndrome (MetS) components including obesity, dyslipidemia, insulin resistance (IR), and hepatic steatosis is rapidly increasing in wealthy societies. It is accepted that inflammation/oxidative stress are involved in the initiation/evolution of the MetS features. The present work was designed to evaluate the effects of three major cellular ROS production systems on obesity, glucose tolerance, and hepatic steatosis development and on oxidative stress onset. To do so, 40 young male Sprague-Dawley rats were divided into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3-HF + MitoQ (mitochondrial ROS scavenger), 4-HF + Apocynin (NADPH oxidase inhibitor), 5-HF + Allopurinol (xanthine oxidase inhibitor). After 8 weeks of these treatments, surrogate MetS, mitochondrial function, and oxidative stress markers were measured in blood and liver. As expected, rats that were fed the HF diet exhibited increased body weight, glucose intolerance, overt hepatic steatosis, and increased hepatic oxidative stress. The impacts of the studied ROS inhibitors on these aspects of the MetS were markedly different. MitoQ showed the most clinically relevant effects, attenuating body weight gain and glucose intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited effects suggesting secondary roles of xanthine oxidase (XO) or NADPH oxidase-dependent ROS production in the onset of oxidative stress-dependent obesity, glucose intolerance, and hepatic steatosis process. Thus, MitoQ revealed the central role of mitochondrial oxidative stress in the development of MetS and suggested that mitochondria-targeted antioxidants may be worth considering as potentially helpful therapies for MetS features