Comparative toxicological analysis of iron, cobalt and nickel nanoparticles in three different in vitro models.

The growing use of engineered nanomaterials (NMs) requires a safety evaluation on their potential health effects. In the present work, we investigated the cytotoxic effects of three zerovalent metallic nanoparticles (NPs): iron nanoparticles (FeNPs), cobalt nanoparticles (CoNPs) and nickel nanoparticles (NiNPs). Iron, cobalt and nickel share similar physicochemical characteristics, such as ferromagnetism, and are known as Iron Triad. Due to their ferromagnetic properties, they are currently under investigation for medical applications as nanovectors for drug delivery, magnetic resonance imaging contrast agents and theranostics. FeNPs represent an innovative technology for the environmental remediation of contaminated groundwater, while NiNPs and CoNPs can be used in industry as information storage, magnetic fluids and catalysts. Cytotoxicity was evaluated using MTS and ATP assays on three different cell lines: carcinomic human alveolar basal epithelial cell line (A549) and murine aneuploid fibrosarcoma cell line (L929) as in vitro models for inhalation and dermal contact, and human hepatocellular liver carcinoma cell line (HepG2) as a liver model. Toxicity results were related to NP dissolution and cellular uptake.Toxicity studies showed dose- and timedependent effects, with CoNPs and NiNPs more toxic than FeNPs in the three in vitro models. The same trend was observed in the presence of their related ions. The different toxicity of NPs did not related to NP or ion internalization. CoNPs and Co2+ showed similar dose-response curves probably due to the high dissolution rate, while NiNPs and FeNPs resulted less toxic than their relative ions (Ni2+ and Fe2+/Fe3+). NiNP dose-response relationship was characterized by a bimodal trend, with the first transition probably due to the NP itself and the second one to the released ions, as confirmed by NiNP cytotoxicity in presence of two different Ni2+ chelators (L-cysteine and L-histidine). In their presence, NiNP showed a unimodal dose-response curve with the maximum effect corresponding to the first transition obtained in the absence of nickel chelators, confirming the role of dissolution in inducing the second transition. The low FeNP toxicity is probably related to their low dissolution and to the physiological role of iron in cell viability and its finely regulated homeostasis. In conclusion, the present study shows differences in FeNP, CoNP and NiNP cytotoxicity relating to NP dissolution and to their elemental composition, in accordance with the presence of cellular mechanisms involved in managing their related ions

Role of polyphenols and polyphenol-rich foods in the modulation of PON1 activity and expression

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme involved in the protection of low-density lipoprotein and HDLs against lipid peroxidation. Several studies documented the capacity of polyphenols to stimulate PON1 transcription activation. The objective of the present review is to provide the main evidence about the role and the potential mechanism of action of polyphenols and polyphenol-rich foods in the modulation of PON1 gene expression and activity. A total of 76 in vitro and in vivo studies were included in the review. Overall, while evidence obtained in vitro is limited to quercetin and resveratrol, those deriving from animal models seem more convincing for a wide range of polyphenols but only at pharmacological doses. Evidence from human studies is promising but deserves more substantiation about the role of polyphenol-rich foods in the regulation of PON1 activity and expression. Research focused on the understanding of the structure\u2013activity relationship of polyphenols with PON1 and on the mechanisms at the base of PON1 modulation is warranted. Well-designed human intervention studies are encouraged to corroborate the findings of polyphenols also at physiological doses

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency : a randomized controlled trial

Background & Aims: Vegetarians and vegans are more vulnerable to vitamin B12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 \ub5g. However, single large oral doses of vitamin B12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B12 (350 \ub5g/week vs. 2000 \ub5g/week) in improving cyanocobalamin (vitamin B12) nutritional status in vegans and vegetarians with a marginal deficiency. Methods: A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 \ub5g/week) and control group Hd (high dose, 2000 \ub5g/week) vitamin B12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B12, related metabolic markers, and blood cell counts. Results: Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time x treatment interaction (P = 0.012) on serum concentration of vitamin B12. In particular, 90 days of supplementation increased the levels of cyanocobalamin (+81.8% in the Ld group and +144.0% in the Hd group) compared to baseline. A significant increase was observed for the levels of holotranscobalamin (+64.5% in the Ld group and +165.2% in the Hd group), while a decrease occurred for the levels of methylmalonic acid (-72.3% in the Ld group and -69.4% in the Hd group), homocysteine (-56.8% in the Ld group and -53.6% in the Hd group), and folate (-22.8% in the Ld group and -17.7% in the Hd group) compared to baseline (time effect, P < 0.0001). No difference was observed between groups (Ld vs. Hd). No effect was detected for the other variables under study. Conclusions: In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 \ub5g/day (350 \ub5g/week) of cobalamin, instead of 2000 \ub5g/week (provided as a single dose), to reach a state of nutritional adequacy of vitamin B12 in this target population

A comprehensive review of healthy effects of vegetarian diets

Aims: A comprehensive review comparing the effect of vegetarian (V) and non-vegetarian (NV) diets on the major cardiometabolic diseases’ outcomes was performed. Data synthesis: We performed literature research (up to December 31, 2022) of the evidence separately for vascular disease (VD), obesity (OB), dyslipidemia (Dysl), hypertension (HPT), type 2 diabetes (T2D), metabolic syndrome (MetS), analyzing only cohort studies and randomized controlled studies (RCTs) and comparing the effect of V and NV diets. Cohort studies showed advantages of V diets compared to NV diets on incidence and/or mortality risk for ischemic heart disease, overweight and OB risk. Most cohort studies showed V had lower risk of HPT and lower blood pressure (BP) than NV and V diets had positive effects on T2D risk or plasma parameters. The few cohort studies on the risk of MetS reported mixed results. In RCTs, V diets, mainly low-fat-vegan ones, led to greater weight loss and improved glycemic control than NV diets and in the only one RCT a partial regression of coronary atherosclerosis. In most RCTs, V diets significantly reduced LDL-C levels (but also decreased HDL-C levels) and BP. Conclusions: In this comprehensive review of the association between V diets and cardiometabolic outcomes, we found that following this type of diet may help to prevent most of these diseases. However, the non-uniformity of the studies, due to ethnic, cultural, and methodological differences, does not allow for generalizing the present results and drawing definitive conclusions. Further, well-designed studies are warranted to confirm the consistency of our conclusions

Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers

This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly (p<0.05) reduced serum levels of total and low-density lipoprotein cholesterol (26.2% and 29.1%, respectively) and transferrin (24.6%). Total n-3, long chain polyunsaturated fatty acids n-3 and docosahexeanoic acid content in erythrocytes increased (p<0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n-3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects

Overview of Human Intervention Studies Evaluating the Impact of the Mediterranean Diet on Markers of DNA Damage

The Mediterranean diet (MD) is characterized by high consumption of fruits, vegetables, cereals, potatoes, poultry, beans, nuts, lean fish, dairy products, small quantities of red meat, moderate alcohol consumption, and olive oil. Most of these foods are rich sources of bioactive compounds which may play a role in the protection of oxidative stress including DNA damage. The present review provides a summary of the evidence deriving from human intervention studies aimed at evaluating the impact of Mediterranean diet on markers of DNA damage, DNA repair, and telomere length. The few results available show a general protective effect of MD alone, or in combination with bioactive-rich foods, on DNA damage. In particular, the studies reported a reduction in the levels of 8-hydroxy-2\u2032\u2013deoxyguanosine and a modulation of DNA repair gene expression and telomere length. In conclusion, despite the limited literature available, the results obtained seem to support the beneficial effects of MD dietary pattern in the protection against DNA damage susceptibility. However, further well-controlled interventions are desirable in order to confirm the results obtained and provide evidence-based conclusions

Berry Fruit Consumption and Metabolic Syndrome

Metabolic Syndrome is a cluster of risk factors which often includes central obesity, dyslipidemia, insulin resistance, glucose intolerance, hypertension, endothelial dysfunction, as well as a pro-inflammatory, pro-oxidant, and pro-thrombotic environment. This leads to a dramatically increased risk of developing type II diabetes mellitus and cardiovascular disease, which is the leading cause of death both in the United States and worldwide. Increasing evidence suggests that berry fruit consumption has a significant potential in the prevention and treatment of most risk factors associated with Metabolic Syndrome and its cardiovascular complications in the human population. This is likely due to the presence of polyphenols with known antioxidant and anti-inflammatory effects, such as anthocyanins and/or phenolic acids. The present review summarizes the findings of recent dietary interventions with berry fruits on human subjects with or at risk of Metabolic Syndrome. It also discusses the potential role of berries as part of a dietary strategy which could greatly reduce the need for pharmacotherapy, associated with potentially deleterious side effects and constituting a considerable financial burden

Scrapie infectivity is quickly cleared in tissues of orally-infected farmed fish

BACKGROUND: Scrapie and bovine spongiform encephalopathy (BSE) belongs to the group of animal transmissible spongiform encephalopathy (TSE). BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM) in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of infection in these species, experimental data on the susceptibility to the BSE agent of farm animals other than sheep and cow are limited only to pigs and domestic chicken. In the framework of a EU-granted project we have challenged two species of fish largely used in human food consumption, rainbow trout (Oncorhynchus mykiss) and turbot (Scophthalmus maximus), with a mouse-adapted TSE strain (scrapie 139A), to assess the risk related to oral consumption of TSE contaminated food. In trout, we also checked the "in vitro" ability of the pathological isoform of the mouse prion protein (PrP(Sc)) to cross the intestinal epithelium when added to the mucosal side of everted intestine. RESULTS: Fish challenged with a large amount of scrapie mouse brain homogenate by either oral or parenteral routes, showed the ability to clear the majority of infectivity load. None of the fish tissues taken at different time points after oral or parenteral inoculation was able to provoke scrapie disease after intracerebral inoculation in recipient mice. However, a few recipient mice were positive for PrP(Sc )and spongiform lesions in the brain. We also showed a specific binding of PrP(Sc )to the mucosal side of fish intestine in the absence of an active uptake of the prion protein through the intestinal wall. CONCLUSION: These results indicate that scrapie 139A, and possibly BSE, is quickly removed from fish tissues despite evidence of a prion like protein in fish and of a specific binding of PrP(Sc )to the mucosal side of fish intestine

Effect of Time and storage temperature on anthocyanin decay and antioxidant activity in wild blueberry (Vaccinium angustifolium) powder

This study evaluated the effects of storage on total and single anthocyanin (ACN) content, and total antioxidant activity (TAA) of freeze-dried wild blueberry (WB) powder maintained at 25, 42, 60, and 80 degrees C for 49 days. Storage reduced single and total ACN content at all of the temperatures; it was slower at 25 degrees C (-3% after 2 weeks), whereas it was faster at 60 degrees C (-60%) and at 80 degrees C (-85%) after 3 days. The values of half-life time (t(1/2)) were found to be 139, 39, and 12 days at 25, 42, and 60 C, respectively, utilizing the Arrhenius equation. No significant effects were detected on TAA by temperature increase. In conclusion, this study provides important information on the stability of WB powder at 25 degrees C; this is interesting scientific research for the food industry