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There is increasing evidence that the excessive generation of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent from the harmful effects of free radicals on human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. In the first step, this approach includes in vitro studies to evaluate the antioxidant activity of the dietary supplements by measuring the parameters of free radical scavenging capacity, of reducing power activity, as well as, their ability to protect biomolecules from oxidation. Furthermore, the evaluation of their antimutagenic and antigenotoxic effects is also presented. SubsequentlySub, the specific effects of the dietary supplements were examined in three cancer cell lines (HepG2, HeLa, MKN45), by measuring redox biomarkers such as glutathione, reactive oxygen species and thiobarbituric acid reactive substances, using flow cytometry and spectrophotometry. Our results indicate that all the dietary supplements exhibit high antioxidant, antimutagenic, antigenotoxic and lipid protective activity. The most prominent result is their capability to induce oxidative damage on cancer cells via the critical decrease of the levels of their intracellular glutathione, as well as the increase of ROS and lipid peroxidation levels after the administration of non-cytotoxic concentrations. We suggest that the proposed methodology could constitute a valuable tool for the characterization of dietary supplements based on their chemical and functional properties. • We evaluated redox related parameters in dietary supplements via two independent stages. • Results reveal antioxidant, antigenotoxic, antimutagenic, and lipid protective activity. • The examination in three cancer cell lines unveil increased GSH and decreased ROS and TBARS. • Equivalent quantity of vitamin C contained in each individual supplement was used in the proposed methodology. • Synergistic effects might overcome the capacity of pure vitamin C contained in supplements, to promote chemoprevention. [ABSTRACT FROM AUTHOR]

It is well-established that long-term fasting improves metabolic health, enhances the total antioxidant capacity and increases well-being. MicroRNAs oversee energy homeostasis and metabolic processes and are widely used as circulating biomarkers to identify the metabolic state. This study investigated whether the expression levels of twenty-four metabolism-associated microRNAs are significantly altered following long-term fasting and if these changes correlate with biochemical and redox parameters in the plasma. Thirty-two participants with an average BMI of 28 kg/m2 underwent a 10-day fasting period with a daily intake of 250 kcal under medical supervision. RT-qPCR on plasma small-RNA extracts revealed that the levels of seven microRNAs (miR-19b-3p, miR-22-3p, miR-122-5p, miR-126-3p, miR-142-3p, miR-143-3p, and miR-145-5p) were significantly altered following fasting. Importantly, the expression levels of these microRNAs have been consistently shown to change in the exact opposite direction in pathological states including obesity, diabetes, nonalcoholic steatohepatitis, and cardiovascular disease. Linear regression analyses revealed that among the microRNAs analyzed, anti-inflammatory miR-146-5p expression displayed most correlations with the levels of different biochemical and redox parameters. In silico analysis of fasting-associated microRNAs demonstrated that they target pathways that are highly enriched for intracellular signaling such mTOR, FoxO and autophagy, as well as extracellular matrix (ECM) interactions and cell-senescence. Overall, these data are consistent with a model in which long-term fasting engages homeostatic mechanisms associated with specific microRNAs to improve metabolic signaling regardless of health status. [Display omitted] • The expression levels of metabolism-associated microRNAs change following long-term fasting in humans. • Fasting microRNA levels change in reverse direction to that observed in human metabolic disorders. • Anti-inflammatory miR-146-5p levels showed most associations with biochemical and redox parameters. • Fasting-associated microRNAs target mTOR, FoxO and autophagy signaling pathways, as well as ECM. [ABSTRACT FROM AUTHOR]

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects. • Long-term fasting increases the antioxidant capacity and decreases oxidative damage. • It improves the metabolic health status. • High TBARS levels at baseline limit the LDL reduction during long-term fasting. • The antioxidant status is related with the lipid lowering effect of long-term fasting. [ABSTRACT FROM AUTHOR]