Haptoglobin Modulates Beta-Amyloid Uptake by U-87 MG Astrocyte Cell Line

Accumulation of beta-amyloid (Aβ) in the extracellular space, which is one of the hallmarks of Alzheimer’s disease (AD), depends on the balance between its synthesis and clearance. The physiological role of extracellular chaperones, capable of affecting early events in the amyloid cascade, is increasingly being investigated by many research groups. Among these proteins, we focused on haptoglobin, which we recently found to form a complex with beta-amyloid in brain tissues or cerebrospinal fluids from patients with AD.We also previously reported that haptoglobin increases with age in rat hippocampus. Major aimof this study was to evaluate whether haptoglobin influences Aβ interaction with astrocytes and its internalization into these cells. Haptoglobin effect on Aβ- induced cell death was also explored. We report here that haptoglobin impairs Aβ uptake by human glioblastoma–astrocytoma cell line U-87 MG and limits the toxicity of this peptide on these cells. Of note, our data also show that Aβ can stimulate haptoglobin release by astrocyte cell lines. The study of the risk of developing AD should be focused not only on the analysis ofAβ but also on the level of critical ligands, such as haptoglobin, able to influence peptide aggregation or clearance

Sweet but Bitter: Focus on Fructose Impact on Brain Function in Rodent Models

Fructose consumption has drastically increased during the last decades due to the extensive commercial use of high-fructose corn syrup as a sweetener for beverages, snacks and baked goods. Fructose overconsumption is known to induce obesity, dyslipidemia, insulin resistance and inflammation, and its metabolism is considered partially responsible for its role in several metabolic diseases. Indeed, the primary metabolites and by-products of gut and hepatic fructolysis may impair the functions of extrahepatic tissues and organs. However, fructose itself causes an adenosine triphosphate (ATP) depletion that triggers inflammation and oxidative stress. Many studies have dealt with the effects of this sugar on various organs, while the impact of fructose on brain function is, to date, less explored, despite the relevance of this issue. Notably, fructose transporters and fructose metabolizing enzymes are present in brain cells. In addition, it has emerged that fructose consumption, even in the short term, can adversely influence brain health by promoting neuroinflammation, brain mitochondrial dysfunction and oxidative stress, as well as insulin resistance. Fructose influence on synaptic plasticity and cognition, with a major impact on critical regions for learning and memory, was also reported. In this review, we discuss emerging data about fructose effects on brain health in rodent models, with special reference to the regulation of food intake, inflammation, mitochondrial function and oxidative stress, insulin signaling and cognitive function

Characterization of blood redox status of early and mid-late lactating dairy cows

The effect of the stage of lactation on blood redox homeostasis of bovine and buffalo cows was evaluated. The investigation was carried out on early lactating and mid-late lactating cows, reared in a farm located in Campania (southern Italy). Plasma concentration of α-tocopherol and ascorbate, the total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase activities were higher (P < 0.01) in mid-late lactating cows, thus suggesting a higher consumption of antioxidants during early lactation. Plasma concentration of protein-bound carbonyls (PC) and nitrotyrosine (N-Tyr), and the level of lipid hydroperoxides (LPO) were higher (P < 0.01) in early lactating cows, thus suggesting that lipid peroxidation and peroxynitrite production are crucial in determining oxidative modifications in plasma. TAC was positively correlated with ascorbate concentration (P < 0.03), and negatively correlated with PC concentration (P < 0.002), and ascorbate was negatively correlated with PC (P < 0.03) in mid-late lactating group. These findings demonstrate that circulating ascorbate plays a major role in preventing protein modifications induced by carbonyls, and that ascorbate scavenging effect is impaired during early lactation. We calculated a protein oxidative stress index as the ratio (PC + N-Tyr)/TAC multiplied by 100, and we found that this parameter was higher (P < 0.0001) in early lactating cows. Therefore, it could be useful for assessing the extent of protein oxidative damage in relation to the whole antioxidant status. Further, we suggest that the LPO/GPx ratio multiplied by 100 might be used as lipid oxidative stress index in lactating cows. This index was higher (P < 0.0001) in early lactating cows, and might represent a standard parameter for evaluating the lipid damage depending on a deficiency of the enzymatic antioxidant defence. These parameters are proposed for a possible effective description of physiological changes associated with lactation

Levels of Soluble Endothelial Protein C Receptor Are Associated with CD4+ Changes in Maraviroc-Treated HIV-Infected Patients

BACKGROUND: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+) cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+) counts both in naïve and experienced subjects compared to traditional antiretroviral therapy. OBJECTIVES AND METHODS: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin) was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up. RESULTS: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+) cell counts (more than 500 cells/µL by week 48). CONCLUSIONS: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+) cells

Extra Virgin Olive Oil Phenols induce authophagy and apoptosis in human bladder cancer cell lines depending on tumor progression

Epidemiological evidences indicate that there is an inverse association between olive oil intake and bladder cancer risk and several data suggest that a key role to support these beneficial effects is played by its phenolic fraction. Bladder cancer is one of the most common cancers in Western countries. In particular, the transitional cell carcinoma histotype shows an aggressive behavior and the current therapies are ineffective. The anti-proliferative effects of an Extra Virgin Olive Oil phenolic Extract (EVOOE) has been investigated on RT112 and J82, two human bladder cancer cell lines employed as models of superficial and invasive bladder cancer, respectively.EVOOE reduces cell viability in both cell lines triggering different processes. In RT112 cells, EVOOE triggers a non-protective autophagic response, evidenced by vacuoles formation and LC-3 lipidation (45%) causing a delay in cell growth (132microg/ml induces 30% reduction). Instead, in J82, the invasive transitional cell carcinoma, EVOOE treatment induces a rapid and remarkable decrease of cell viability (33 microg/ml for 24 h induces 40% reduction) triggering an apoptotic process, evidenced with Annexin V positivity and the increased activity of caspases 3 and 9. EVOOE exerts an antioxidant activity in both cell lines reducing ROS (30% in J82 and 15% in RT112) and increasing GSH level (20% in J82 and 40% in RT112). However, comparing the effects of EVOOE with those of other well-known antioxidants, the absence of correlation between antioxidant effects and reduced cell viability was evidenced. Moreover, using an inhibitor of GSH synthesis, we demonstrated that EVOOE acts independently from GSH modulation.Data presented show that EVOOE possesses pleiotropic activities that intercept different pathways resulting in anti-proliferative effects independently of its antioxidant propert

A new role of red wine in modulating erythrocytes antioxidant defense

Dealcoholated red wine has been shown to exert protective effects, reducing the risk of cardiovascular events by improving endothelium-dependent vasodilation and inhibiting platelet aggregation These biological activities have been associated with the polyphenolic components of red wine, suggesting that the pool of phenolic compounds, including flavonoids and anthocyanins, could be responsible for its functional effects. The concept that antioxidant properties of polyphenols could explain the beneficial effects of red wine has been carried forward. Here, we hypothesize a new role of red wine in modulating oxidative stress, leading to the alteration of the antioxidant potential in humans. We previously demonstrated that red wine polyphenols (RWp) protect human erythrocytes from oxidative stress by the activation of an important enzymatic system involved in neutralizing plasma free radicals, namely Plasma Membrane Redox System (PMRS). The present work investigates the underlying mechanism triggered by RWp in the activation of PMRS via the involvement of intracellular GSH. Hence, the increase of GSH intracellular concentration results from the activation of GSH-dependent enzymes, namely glutathione reductase and glucose-6-phosphate dehydrogenase, of about 30% and 50% respectively after 2 min of incubation of human erythrocytes in the presence of RWp (73 ug/ml Gallic Acid Equivalents). Changes in GSH pathway induced by RW were associated with a slight but significant increase (about 15%) of ROS (reactive oxygen species) concentration. We conclude that the pro-oxidant effect of RWp promotes an adaptive stress response in human erythrocytes, which improves their antioxidant defense protecting them from oxidative stress

Galacto-Oligosaccharide/Polidextrose Enriched Formula Protects against Respiratory Infections in Infants at High Risk of Atopy: A Randomized Clinical Trial

Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide/polydextrose (GOS/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes

Analysis of plasma indices of redox homeostasis in dairy cows reared in polluted areas of Piedmont (northern Italy)

Steel manufacturing is responsible for the emission of pollutants, including dioxins and transition metals, inducing reactive oxygen species generation and DNA damage. Dioxin pollution represents the major cause of milk and dairy product contamination, in Italy, and is associated with oxidative stress-related processes, that may impair health and performance of cows.We evaluated the effect of exposure to different concentrations of pollutants derived from steel manufacturing on blood redox homeostasis of bovine cows. We analyzed two groups of dairy cows (A, B), reared in two different polluted areas, and a control group of cows bred in an industry free area. The extent of exposure to contaminants was defined by measuring dioxin level in bulk milk samples collected from animals of each farm. This level was lower in milk of group A than in group B. Plasma concentrations of retinol, alpha-tocopherol and ascorbate, the total antioxidant capacity, and the activities of superoxide dismutase and glutathione peroxidase were higher in control group than in exposed groups. In particular, retinol and tocopherol levelswere higher in the groupwith lower milk dioxin level. Plasma titers of protein-bound carbonyls (PC), nitro-tyrosine, and hydroperoxideswere lower in control group than in A or B. Hydroperoxides and PC plasmaconcentrationswere increased in the groupwith higher milk concentration of dioxin. Our results demonstrate that, irrespective of the nature of chemicals inducing oxidativemodifications, the extent of damage to plasmaprotein and lipid, is correlatedwith the concentration of dioxin in milk. So, the characterization of blood redox status might be a useful tool for identifying animals exposed to environmental pollutants. Plasma concentrations of retinol, alpha-tocopherol, PC and hydroperoxides could therefore represent good indices of the extent of animal exposure, as they significantly change in groups with different milk concentrations of dioxi