30 research outputs found
Different effects of anthocyanins and phenolic acids from wild blueberry (Vaccinium angustifolium) on monocytes adhesion to endothelial cells in a TNF-alpha stimulated proinflammatory environment
No full textSCOPE:
Monocyte adhesion to the vascular endothelium is a crucial step in the early stages of atherogenesis. This study aims to investigate the capacity of an anthocyanin (ACN) and phenolic acid (PA)-rich fraction (RF) of a wild blueberry, single ACNs (cyanidin, malvidin, delphinidin) and related metabolites (protocatechuic, syringic and gallic acid) to counteract monocytes (THP-1) adhesion to endothelial cells (HUVECs) in a tumor necrosis α (TNF-α) mediated pro-inflammatory environment.
METHODS AND RESULTS:
HUVECs were incubated with different concentrations (from 0.01 to 10 μg mL-1 ) of the compounds for 24 h. Labelled monocytic THP-1 cells were added to HUVECs and their adhesion was induced by TNF-α (100 ng mL-1 ). ACN-RF reduced THP-1 adhesion to HUVECs with a maximum effect at 10 μg mL-1 (-33%). PA-RF counteracted THP-1 adhesion at 0.01, 0.1 and 1 μg mL-1 (-45%, -48.7% and -27.6%, respectively), but not at maximum concentration. Supplementation with gallic acid reduced THP-1 adhesion to HUVECs with a maximum effect at 1 μg mL-1 (-29.9%), while malvidin-3-glucoside and syringic acid increased the adhesion. No effect was observed for the other compounds.
CONCLUSION:
These results suggest that ACNs/PA-RF may prevent atherogenesis while the effects of the single ACNs and metabolites are controversial and merit further exploration
Study of the potential anti-atherosclerotic effect of polyphenols from wild blueberry (Vaccinium angustifolium) in endothelial cells : preliminary data
No full textBackground: Atherosclerosis is a disease affecting arterial blood vessels caused largely by the accumulation of macrophages and white blood cells and promoted by low-density lipoproteins. Polyphenols may prevent atherosclerosis by reducing oxidative stress, inflammation, and by increasing the production of vasodilators such as nitric oxide.
Aim: This study aims to investigate the capacity of an anthocyanin (ACN) and phenolic acid (PA)-rich fraction, obtained from a wild blueberry powder, to counteract early events in atherosclerosis in an in vitro cell model system.
Methods: The anti-atheroclerotic effect of the two fractions was tested in human umbilical vein endothelial cells (HUVECs) commonly used as the in vitro model for the study of the function of endothelial cells. HUVECs were incubated with different concentrations (from 0.05 to 10 μg mL-1) of ACN and PA-rich fraction for 24h. Labelled monocytic THP-1 cells were added to HUVEC culture and the adhesion was promoted by stimulating a pro-inflammatory status with TNF- (1 μg mL-1). After 24h incubation, the attachment of THP-1 to HUVEC was measured through a fluorescence spectrophotometer and the fold-increase in THP-1 attachment with respect to the control (without stimulation with TNF-) was calculated. Results were analysed by ANOVA. Post-hoc analysis of differences between treatments was assessed by the Least Significant Difference (LSD) test with p ≤ 0.05 as level of statistical significance.
Results: We documented that ACN and PA-rich fractions reduced THP-1 attachment to HUVEC cells following stimulation with the pro-inflammatory cytokine. In particular, ACN-rich fraction showed a positive and significant effect at the concentration of 10 μg mL-1 (-33%, p=0.04), while the PA-rich fraction was able to reduce significantly THP-1 attachment at the low doses (0.05, 0.1 and 0.3 μg mL-1, -45%, -49% and -51%, respectively).
Conclusions: These preliminary results demonstrated a potential role of polyphenol compounds in the prevention of atherosclerotic process by reducing the THP-1 attachment to HUVEC cells. Moreover, the effects were observed also at the low concentrations, supporting a possible contribution at concentrations comparable with those achievable in vivo. The role of ACNs, their metabolites and the molecular mechanisms involved in such modulation are under study
Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium) powder counteract lipid accumulation in THP-1-derived macrophages
No full textPurpose: Blueberries are a rich source of anthocyanins (ACNs) and phenolic acids (PA), which are hypothesized to protect against development of atherosclerosis. The present study examined the effect of an ACN- and PA-rich fractions, obtained from a wild blueberry powder, on the capacity to counteract lipid accumulation in macrophages derived from monocytic THP-1 cells. In addition, we tested the capacity of pure ACNs and their metabolites to alter lipid accumulation.Methods: THP-1-derived macrophages were incubated with fatty acids (500 μM oleic/palmitic acid, 2:1 ratio) and different concentrations (from 0.05 to 10 μg mL−1) of ACN- and PA-rich fractions, pure ACN standards (malvidin, delphinidin and cyanidin 3-glucoside), and metabolites (syringic, gallic and protocatechuic acids). Lipid accumulation was quantified with the fluorescent dye Nile red.Results: Lipid accumulation was reduced at all concentrations of the ACN-rich fraction tested with a maximum reduction at 10 μg mL−1 (−27.4 %; p < 0.0001). The PA-rich fraction significantly reduced the lipid accumulation only at the low concentrations from 0.05 μg mL−1 to 0.3 μg mL−1, with respect to the control with fatty acids. Supplementation with pure ACN compounds (malvidin and delphinidin-3-glucoside and its metabolic products (syringic and gallic acid)) reduced lipid accumulation especially at the low concentrations, while no significant effect was observed after cyanidin-3-glucoside and protocatechuic acid supplementation.Conclusions: The results demonstrated a potential role of both the ACN- and PA-rich fractions and single compounds in the lipid accumulation also at concentrations close to that achievable in vivo
Repair activity of oxidatively damaged DNA and telomere length in human lung epithelial cells after exposure to multi-walled carbon nanotubes.
No full textOne type of carbon nanotubes (CNTs) (MWCNT-7, from Mitsui) has been classified as probably carcinogenic to humans, however insufficient data does not warrant the same classification for other types of CNTs. Experimental data indicate that CNT exposure can result in oxidative stress and DNA damage in cultured cells, whereas these materials appear to induce low or no mutagenicity. Therefore, the present study aimed to investigate whether in vitro exposure of cultured airway epithelial cells (A549) to multi-walled CNTs (MWCNTs) could increase the DNA repair activity of oxidatively damaged DNA and drive the cells toward replicative senescence, assessed by attrition of telomeres. To investigate this, H2O2 and KBrO3 were used to induce DNA damage in the cells and the effect of pre-exposure to MWCNT tested for a change in repair activity inside the cells or in the extract of treated cells. The effect of MWCNT exposure on telomere length was investigated for concentration and time response. We report a significantly increased repair activity in A549 cells exposed to MWCNTs compared to non-exposed cells, suggesting that DNA repair activity may be influenced by exposure to MWCNTs. The telomere length was decreased at times longer than 24h, but this decrease was not concentration dependent. The results suggest that the seemingly low mutagenicity of CNTs in cultured cells may be associated with an increased DNA repair activity and a replicative senescence, which may counteract the manifestation of DNA lesions to mutations
Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice.
No full textThe utilisation of nanoparticles as the means of targeted delivery of therapeutics and/or imaging agents could greatly enhance the specific transport of biologically active payloads to target tissues while avoiding or reducing undesired side-effects. To allow for this to become a reality, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models and in vitro − (HepG2 cells). The data demonstrated that intravenous injection of liposomes did not cause any significant in vivo hepatic toxicity (inflammation, alterations in blood parameters, anti-oxidant depletion, acute phase response and histopathology) at doses of 200 μg per mouse in either healthy or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked
Synergistic Effects of Zinc Oxide Nanoparticles and Fatty Acids on Toxicity to Caco-2 Cells
No full textFatty acids exposure may increase sensitivity of intestinal epithelial cells to cytotoxic effects of zinc oxide (ZnO) nanoparticles (NPs). This study evaluated the synergistic effects of ZnO NPs and palmitic acid (PA) or free fatty acids (FFAs) mixture (oleic/PA 2:1) on toxicity to human colon epithelial (Caco-2) cells. The ZnO NPs exposure concentration dependently induced cytotoxicity to Caco-2 cells showing as reduced proliferation and activity measured by 3 different assays. PA exposure induced cytotoxicity, and coexposure to ZnO NPs and PA showed the largest cytotoxic effects. The presence of FFAs mixture did not affect the ZnO NPs-induced cytotoxicity. Filtration of freshly prepared suspension of NPs through a 0.45-µm pore size membrane significantly reduced the cytotoxicity, indicating a role of concentration or size of particles in cytotoxic effects. The ZnO NPs and PA coexposure induced production of mitochondrial reactive oxygen species (mROS) but not intracellular ROS production, whereas FFAs mixture exposure did not induce mROS and inhibited intracellular ROS. Both ZnO NPs and fatty acids (PA and FFAs mixture) promoted lysosomal destabilization, which was not correlated with cytotoxicity. These results indicated that PA can enhance ZnO NPs-induced cytotoxicity probably by the augmentation of mROS production, whereas FFAs mixture did not affect ROS production. Synergistic effects between ZnO NPs and fatty acids may be important when considering NPs toxicity via oral exposure.</p
Hepatic hazard assessment of silver nanoparticle exposure in healthy and chronically alcohol fed mice.
No full textSilver (Ag) nanoparticles (NPs) are currently among one of the most widely used nanomaterials. This in turn, implies an increased risk of human and environmental exposure. Alcohol abuse is a global issue with millions of people in the general population affected by the associated adverse effects. The excessive consumption of alcohol is a prominent cause of chronic liver disease which manifest in multiple disorders. In this study, the adverse health effects of Ag NP exposure were investigated in models of alcoholic hepatic disease in vitro and in vivo. The data showed that Ag NP induced hepatic health effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ’s ability for recovery post-NP challenge. Additionally, it is demonstrated that the in vivo data correlated well with in vitro findings where ethanol pretreatment of hepatocytes resulted in significantly increased inflammatory response post-Ag NP exposure. To the best of our knowledge this is the first study of its kind to investigate nano-sized material-induced hepatic pathology in models representative of susceptible individuals (those with pre-existing alcohol liver disease) within the population. This is an area of research in the field of nanotoxicology, and in particular with regard to NP risk assessment that is almost entirely overlooked
Alcohol consumption induces Th2 deviation of the immune response in mice exposed to ovalbumin
No full textUdgivelsesdato: 200
Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice
No full textBackground: Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues. Results: All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure. Conclusion: Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles.</p
Comparison of acute phase response in mice after inhalation and intratracheal instillation of molybdenum disulphide and tungsten particles
No full textInhalation studies are the gold standard for assessing the toxicity of airborne materials. They require considerable time, special equipment, and large amounts of test material. Intratracheal instillation is considered a screening and hazard assessment tool as it is simple, quick, allows control of the applied dose, and requires less test material. The particle-induced pulmonary inflammation and acute phase response in mice caused by intratracheal instillation or inhalation of molybdenum disulphide or tungsten particles were compared. End points included neutrophil numbers in bronchoalveolar lavage fluid, Saa3 mRNA levels in lung tissue and Saa1 mRNA levels in liver tissue, and SAA3 plasma protein. Acute phase response was used as a biomarker for the risk of cardiovascular disease. Intratracheal instillation of molybdenum disulphide or tungsten particles did not produce pulmonary inflammation, while molybdenum disulphide particles induced pulmonary acute phase response with both exposure methods and systemic acute phase response after intratracheal instillation. Inhalation and intratracheal instillation showed similar dose–response relationships for pulmonary and systemic acute phase response when molybdenum disulphide was expressed as dosed surface area. Both exposure methods showed similar responses for molybdenum disulphide and tungsten, suggesting that intratracheal instillation can be used for screening particle-induced acute phase response and thereby particle-induced cardiovascular disease.Atmospheric Remote Sensin
