Protective Effects of Walnut Extract Against Amyloid Beta Peptide-Induced Cell Death and Oxidative Stress in PC12 Cells

Amyloid beta-protein (Aβ) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimer’s disease. Aβ is known to increase free radical production in neuronal cells, leading to oxidative stress and cell death. Recently, considerable attention has been focused on dietary antioxidants that are able to scavenge reactive oxygen species (ROS), thereby offering protection against oxidative stress. Walnuts are rich in components that have anti-oxidant and anti-inflammatory properties. The inhibition of in vitro fibrillization of synthetic Aβ, and solubilization of preformed fibrillar Aβ by walnut extract was previously reported. The present study was designed to investigate whether walnut extract can protect against Aβ-induced oxidative damage and cytotoxicity. The effect of walnut extract on Aβ-induced cellular damage, ROS generation and apoptosis in PC12 pheochromocytoma cells was studied. Walnut extract reduced Aβ-mediated cell death assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction, and release of lactate dehydrogenase (membrane damage), DNA damage (apoptosis) and generation of ROS in a concentration-dependent manner. These results suggest that walnut extract can counteract Aβ-induced oxidative stress and associated cell death

Evaluation of chromium in red blood cells as an indicator of exposure to hexavalent chromium: An in vitro study

International audienceChromium(VI) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and whole blood (i.e., including plasma) are indicative of recent exposure, chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure. Before recommending Cr in RBC as a biological indicator of Cr(VI) exposure, in-vitro studies must be undertaken to assess its reliability. The present study examines the relationship between the chromium added to a blood sample and that subsequently found in the RBC. After incubation of total blood with chromium, RBC were isolated, counted and their viability assessed. Direct analysis of chromium in RBC was conducted using Atomic Absorption Spectrometry. Hexavalent, but not trivalent Cr, was seen to accumulate in the RBC and we found a strong correlation between the Cr(VI) concentration added to a blood sample and the amount of Cr in RBC. This relationship appears to be independent of the chemical properties of the human blood samples (e.g., different blood donors or different reducing capacities). Even though in-vivo studies are still needed to integrate our understanding of Cr(VI) toxicokinetics, our findings reinforce the idea that a single determination of the chromium concentration in RBC would enable biomonitoring of critical cases of Cr(VI) exposure.Bien que les travailleurs puissent être exposés à du chrome métallique, du Cr (III) et du Cr (VI) sur le lieu de travail, les composés du Cr (VI) sont particulièrement préoccupants en termes de risques pour la santé. Après absorption par ingestion, inhalation et / ou diffusion percutanée, les ions Cr (VI) sont transportés dans le sang et pénètrent les globules rouges. En raison de la réduction intracellulaire du Cr (VI) en Cr (III) et en même temps, de leur liaison aux protéines, les globules rouges représentent un organe cible facilement accessible pour la détermination quantitative de chrome après une exposition aux composés du Cr (VI). Alors que les mesures de chrome dans l'urine et le sang total (y compris le plasma) sont révélateurs d'une exposition récente, le chrome dans les globules rouges est attribuable spécifiquement à une exposition au Cr (VI) et ce, pendant une période correspondant à la durée de vie des globules - une période d'exposition beaucoup plus longue.Avant que le Cr dans les globules rouges puisse être utilisé comme un indicateur biologique d'exposition (IBE) au Cr (VI), sa fiabilité doit être évaluée dans des études in vitro. On examine la relation entre le chrome ajouté à un échantillon de sang et à la quantité de Cr retrouvée dans les globules. L'influence de l'état d'oxydation du Cr, sa spéciation, les paramètres d'incubation, la concentration d'acide ascorbique et l’influence des donneurs de sang ont été étudiés. Bien que des études in-vivo soient encore nécessaires pour mieux comprendre la toxicocinétique du Cr (VI), nos résultats suggèrent que le Cr dans GR devrait sérieusement être considéré comme un IBE pour Cr (VI)

Activation of T cells by dendritic cells exposed to a reference sensitizer Towards a promising model to assess the allergenic potential of chemicals

International audienceBackground - Low molecular weight chemicals constitute one of the major causes of occupational allergies. European legislation on chemicals recommends limiting the use of in vivo models for assessing the sensitizing potential of chemicals, and encourages the development of integrated alternative methods. An in vitro mouse model of bone marrow-derived dendritic cells (BMDCs) that showed good accuracy (75%) and sensitivity (69%) has previously been developed to assess the sensitizing potential of chemicals. Objective - To assess the ability of BMDCs to activate T cells (TCs) in vitro. Methods - BMDCs pre-exposed to the reference sensitizer ammonium hexachloroplatinate (AHCP) were co-cultured with different subpopulations of TCs. TC activation was assessed by surface marker expression, proliferation, and cytokine release. Results - The results showed significant activation of TCs co-cultured with dendritic cells pre-exposed to AHCP as evaluated by CD124 expression, proliferation, and cytokine secretion. Moreover, the response of TCs appeared to be Th2-oriented. Naive TCs were shown to be involved in this response, and the removal of regulatory TCs did not improve the cell response. Conclusions - The BMDCs used in this previously developed model appear to have the ability to activate TCs, confirming that the BMDC model represents a reliable assay for assessing the sensitizing potential of chemicals