Functionalization of selenium nanoparticles with olive polyphenols - impact on toxicity and antioxidative activity.

Selenium nanoparticles (SeNPs) represent novel selenium (Se) formulation characterized by improved biocompatibility and a wider therapeutic range in comparison to inorganic Se. The aim of this work was to investigate the possibilities of functionalization of SeNPs with olive pomace extract (OPE), rich in health-promoting polyphenols, and to obtain innovative forms of nutraceuticals. Cytotoxic and antioxidative activities of four types of SeNPs (polyvinylpyrrolidone stabilized (PVP SeNPs), polysorbate stabilized (PS SeNPs), polyvinylpyrrolidone stabilized and functionalized using OPE (f PVP SeNPs) and polysorbate stabilized and functionalized using OPE (f PS SeNPs) were investigated. SeNPs showed lower toxicity on human hepatocellular carcinoma (HepG2) and human colorectal adenocarcinoma (Caco2) cells compared to selenite. Functionalization with polyphenols significantly improved their direct antiradical (f PVP SeNPs: 24.4 ± 1.84 and f PS SeNPs: 30.9 ± 2.47 mg TE/mmol Se) and reducing properties (f PVP SeNPs: 50 ± 3.16 and f PS SeNPs: 53.6 ± 3.22 mg GAE/mmol) compared to non-functionalized SeNPs. The significant impact of tested SeNPs on intracellular antioxidative mechanisms has been observed and it was dependent on both cell type and physico-chemical properties of SeNPs, indicating the complexity of involved mechanisms.

Effect of Alpha Lipoic Acid Supplementation on Oxidative Stress and Lipid Parameters in Women Diagnosed with Low-Grade Squamous Intraepithelial Lesions (LSILs): A Double-Blind, Randomized, Placebo-Controlled Trial.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients' initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Phyto-Assisted Synthesis of Nanoselenium-Surface Modification and Stabilization by Polyphenols and Pectins Derived from Agricultural Wastes.

Raw and purified mandarin peel-derived pectins were characterized and combined with olive pomace extract (OPE) in the green synthesis of selenium nanoparticles (SeNPs). SeNPs were characterized in terms of size distribution and zeta potential, and their stability was monitored during 30 days of storage. HepG2 and Caco-2 cell models were used for the assessment of biocompatibility, while antioxidant activity was investigated by the combination of chemical and cellular-based assays. SeNP average diameters ranged from 171.3 nm up to 216.9 nm; smaller SeNPs were obtained by the utilization of purified pectins, and functionalization with OPE slightly increased the average. At concentrations of 15 mg/L SeNPs were found to be biocompatible, and their toxicity was significantly lower in comparison to inorganic selenium forms. Functionalization of SeNPs with OPE increased their antioxidant activity in chemical models. The effect was not clear in cell-based models, even though all investigated SeNPs improved cell viability and protected intracellular reduced GSH under induced oxidative stress conditions in both investigated cell lines. Exposure of cell lines to SeNPs did not prevent ROS formation after exposure to prooxidant, probably due to low transepithelial permeability. Future studies should focus on further improving the bioavailability/permeability of SeNPs and enhancing the utilization of easily available secondary raw materials in the process of phyto-mediated SeNP synthesis.

Effect of Alpha-Lipoic Acid Supplementation on Low-Grade Squamous Intraepithelial Lesions-Double-Blind, Randomized, Placebo-Controlled Trial.

Low-grade squamous intraepithelial lesion (SIL) is a cytologic diagnosis etiologically related to human papilloma virus (HPV) infection that leads to the release of inflammation mediators, the formation of reactive oxygen species (ROS) and decreased levels of antioxidants in tissues, which is why antioxidants might be considered effective against SIL progression. This randomized double-blind placebo-controlled study aimed to investigate the effectiveness of alpha-lipoic acid (ALA) supplementation (600 mg/day) on the regression of low-grade SIL in 100 patients. Low-grade SIL was determined after the cytological screening, colposcopic examination and targeted biopsy and histological confirmation of cytological−colposcopic diagnosis. Inflammation parameters and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle habits were investigated using a standardized and validated semi-quantitative food questionnaire (FFQ). ALA supplementation significantly reduced the proportion of patients with low-grade cytological abnormalities, in comparison to placebo. Given the obtained level of significance (p < 0.001), the presented results indicate that short-term ALA supplementation shows a clinically significant effect on cervical cytology. Future studies should focus on the use of innovative formulations of ALA that might induce bioavailability and therapeutic efficiency against HPV infection and the investigation of synergistic effects of concurrent dietary/lifestyle modification and ALA supplementation in both low-grade and high-grade SIL.

Utilization of Olive Pomace in Green Synthesis of Selenium Nanoparticles: Physico-Chemical Characterization, Bioaccessibility and Biocompatibility.

Olive pomace extract (OPE) was investigated as a potential surface modifier for the development of the green synthesis process of selenium nanoparticles (SeNPs). In order to evaluate them as potential nutraceuticals, the obtained nanosystems were characterized in terms of size distribution, shape, zeta potential, stability in different media, gastrointestinal bioaccessibility and biocompatibility. Systems with a unimodal size distribution of spherical particles were obtained, with average diameters ranging from 53.3 nm to 181.7 nm, depending on the type of coating agent used and the presence of OPE in the reaction mixture. The nanosystems were significantly affected by the gastrointestinal conditions. Bioaccessibility ranged from 33.57% to 56.93% and it was significantly increased by functionalization of with OPE. Biocompatibility was investigated in the HepG2 and Caco2 cell models, proving that they had significantly lower toxicity in comparison to sodium selenite. Significant differences were observed in cellular responses depending on the type of cells used, indicating differences in the mechanisms of toxicity induced by SeNPs. The obtained results provide new insight into the possibilities for the utilization of valuable food-waste extracts in the sustainable development of nanonutraceuticals.