Concentration Dependence of Anti- and Pro-Oxidant Activity of Polyphenols as Evaluated with a Light-Emitting Fe2+-Egta-H2O2 System.

Hydroxyl radical (•OH) scavenging and the regeneration of Fe2+ may inhibit or enhance peroxidative damage induced by a Fenton system, respectively. Plant polyphenols reveal the afore-mentioned activities, and their cumulative net effect may determine anti- or pro-oxidant actions. We investigated the influence of 17 phenolics on ultra-weak photon emission (UPE) from a modified Fenton system (92.6 µmol/L Fe2+, 185.2 µmol/L EGTA (ethylene glycol-bis(ß-aminoethyl-ether)-N,N,N',N,-tetraacetic acid) and 2.6 mmol/L H2O2 pH = 7.4). A total of 8 compounds inhibited (antioxidant effect), and 5 enhanced (pro-oxidant effect) UPE at all studied concentrations (5 to 50 µmol/L). A total of 4 compounds altered their activity from pro- to antioxidant (or vice versa) along with increasing concentrations. A total of 3 the most active of those (ferulic acid, chlorogenic acid and cyanidin 3-O-glucoside; mean UPE enhancement by 63%, 5% and 445% at 5 µmol/L; mean UPE inhibition by 28%, 94% and 24% at 50 µmol/L, respectively) contained catechol or methoxyphenol structures that are associated with effective •OH scavenging and Fe2+ regeneration. Most likely, these structures can determine the bidirectional, concentration-dependent activity of some phenolics under stable in vitro conditions. This is because the concentrations of the studied compounds are close to those occurring in human fluids, and this phenomenon should be considered in the case of dietary supplementation with isolated phenolics.

Effect of Physiological Concentrations of Vitamin C on the Inhibitation of Hydroxyl Radical Induced Light Emission from Fe2+-EGTA-H2O2 and Fe3+-EGTA-H2O2 Systems In Vitro.

Ascorbic acid (AA) has antioxidant properties. However, in the presence of Fe2+/Fe3+ ions and H2O2, it may behave as a pro-oxidant by accelerating and enhancing the formation of hydroxyl radicals (•OH). Therefore, in this study we evaluated the effect of AA at concentrations of 1 to 200 µmol/L on •OH-induced light emission (at a pH of 7.4 and temperature of 37 °C) from 92.6 µmol/L Fe2+-185.2 µmol/L EGTA (ethylene glycol-bis (ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid)-2.6 mmol/L H2O2, and 92.6 µmol/L Fe3+-185.2 µmol/L EGTA-2.6 mmol/L H2O2 systems. Dehydroascorbic acid (DHAA) at the same range of concentrations served as the reference compound. Light emission was measured with multitube luminometer (AutoLumat Plus LB 953) for 120 s after automatic injection of H2O2. AA at concentrations of 1 to 50 µmol/L and of 1 to 75 µmol/L completely inhibited light emission from Fe2+-EGTA-H2O2 and Fe3+-EGTA-H2O2, respectively. Concentrations of 100 and 200 µmol/L did not affect chemiluminescence of Fe3+-EGTA-H2O2 but tended to increase light emission from Fe2+-EGTA-H2O2. DHAA at concentrations of 1 to 100 µmol/L had no effect on chemiluminescence of both systems. These results indicate that AA at physiological concentrations exhibits strong antioxidant activity in the presence of chelated iron and H2O2.

Light emission from the Fe2+ -EDTA-ascorbic acid-H2 O2 system strongly enhanced by plant phenolic acids.

Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra-weak photon emission (UPE). We investigated the UPE from the Fe2+ -EDTA (ethylenediaminetetraacetic acid)-AA (ascorbic acid)-H2 O2 (hydrogen peroxide) system with a multitube luminometer (Peltier-cooled photon counter, spectral range 380-630 nm). The UPE, of 92.6 µmol/L Fe2+ , 185.2 µmol/L EDTA, 472 µmol/L AA, 2.6 mmol/L H2 O2 , reached 1217 ± 118 relative light units during 2 min measurement and was about two times higher (P < 0.001) than the UPE of incomplete systems (Fe2+ -AA-H2 O2 , Fe2+ -EDTA-H2 O2 , AA-H2 O2 ) and medium alone. Substitution of Fe2+ with Cr2+ , Co2+ , Mn2+ or Cu2+ as well as of EDTA with EGTA (ethylene glycol-bis(ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid) or citrate powerfully inhibited UPE. Experiments with scavengers of reactive oxygen species (dimethyl sulfoxide, mannitol, sodium azide, superoxide dismutase) revealed the dependence of UPE only on hydroxyl radicals. Dimethyl sulfoxide at the concentration of 0.74 mmol/L inhibited UPE by 79 ± 4%. Plant phenolics (ferulic, chlorogenic and caffec acids) at the concentration of 870 µmol/L strongly enhanced UPE by 5-, 13.9- and 46.8-times (P < 0.001), respectively. It is suggested that augmentation of UPE from Fe2+ -EDTA-AA-H2 O2 system can be applied for detection of these phytochemicals.

Light Emission from the Fe2+-EGTA-H2O2 System: Possible Application for the Determination of Antioxidant Activity of Plant Phenolics.

Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra-weak photon emission (UPE). We investigated the UPE from the Fe2+-EGTA (ethylene glycol-bis(ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid)-H2O2 system with a multitube luminometer (Peltier-cooled photon counter, spectral range 380 to 630 nm). The UPE of 92.6 µmol/L Fe2+-185.2 µmol/L EGTA-2.6 mmol/L H2O2 reached 4319 ± 755 relative light units during 2 min measurement and was about seven times higher (p < 0.001) than the UPE of incomplete systems (Fe2+-H2O2, EGTA-H2O2) and medium alone. Substitution of Fe2+ with Cr2+, Co2+, Mn2+ or Cu2+ as well as of EGTA with EDTA (ethylenediaminetetraacetic acid) or citrate completely abolished UPE. Experiments with ROS scavengers revealed the dependence of UPE on hydroxyl radicals suggesting occurrence of oxidative attack and cleavage of the ether bond in EGTA backbone structure and formation of triplet excited carbonyl groups with subsequent light emission. Plant phenolics (ferulic, chlorogenic and caffec acids) at concentration 87 µmol/L and ascorbate at 0.46 mmol/L inhibited UPE by 90 ± 4%, 90 ± 5%, 97 ± 2% and 92 ± 1%, respectively. Quenching of UPE from Fe2+-EGTA-H2O2 system can be used for evaluation of antioxidant activity of phytochemicals.

Strawberries Added to the Usual Diet Suppress Fasting Plasma Paraoxonase Activity and Have a Weak Transient Decreasing Effect on Cholesterol Levels in Healthy Nonobese Subjects.

OBJECTIVE: Strawberries can improve oxidants-antioxidants balance and reduce some cardiovascular risk factors in obese subjects. Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated enzyme with antioxidant properties that can protect from coronary artery disease in humans. We examined the effect of strawberry consumption on plasma PON-1 activity and lipid profile in healthy nonobese subjects. METHODS: Thirty-one subjects (body mass index [BMI] 24.4 ± 4.0 kg/m(2)) on their usual diet consumed 500 g of strawberry pulp daily for 30 days (first course) and after a 10-day washout the cycle was repeated (second course). Fasting blood and spot morning urine samples were collected before, during, and after each strawberry course (8 time points) for determination of paraoxonase and arylesterase PON-1 activities and lipid profile. Twenty subjects served as controls with respect to cholesterol and PON-1 activities changes over the study period. RESULTS: Strawberries decreased mean plasma paraoxonase PON-1 activity and this effect was more evident after the second course (by 11.6%, p < 0.05) than after the first course (5.4%, p = 0.06), whereas arylesterase activity was constant. Strawberries altered total cholesterol levels (p < 0.05) with a tendency to transiently decrease it (by 5.1%) only after 15 days of the first course. Triglycerides and high- and low-density lipoprotein cholesterol did not change in response to fruit consumption. No changes in PON-1 activities and lipid profile were noted in controls. Paraoxonase correlated with arylesterase activity (Æ¿ from 0.33 to 0.46 at the first 7 time points, p < 0.05). This association disappeared at the end of study (Æ¿ = 0.07) when the strongest inhibition of paraoxonase was noted. CONCLUSIONS: Supplementation of the usual diet with strawberries decreased paraoxonase PON-1 activity and did not improve lipid profiles in healthy nonobese subjects. Further studies are necessary to establish the clinical significance of paraoxonase suppression and to define a group of healthy subjects who can benefit from strawberry consumption with respect to cholesterol levels.

Glucocorticoids Induce Partial Remission of Focal Segmental Glomerulosclerosis but Not Interstitial Nephritis in COVID-19 Acute Kidney Injury in an APOL1 Low-Risk Genotype White Patient.

BACKGROUND COVID-19 can be complicated by kidney disease, including focal segmental glomerulosclerosis (FSGS), interstitial nephritis, and acute kidney injury (AKI). Almost all known cases of COVID-19-associated glomerulonephritis have been in patients of African descent, with G1 or G2 apolipoprotein L1 (APOL1) risk alleles, and they presented collapsing type of FSGS. CASE REPORT We report a case of biopsy-confirmed non-collapsing FSGS with secondary acute interstitial nephritis and AKI in a young White man with APOL1 low-risk genotype, who had COVID-19 pneumonia. His past history included arterial hypertension, anabolic steroids, and high-protein diet. He fully recovered from type 1 respiratory failure and AKI after transfusion of COVID-19 convalescent plasma and intravenous treatment with dexamethasone administered for 16 days in a dose reduced from 16 to 2 mg/day. Due to progressing severe nephrotic proteinuria (22.6 g/24 h), intravenous methylprednisolone was administered (1500 mg divided in 3 pulses over 3 days) immediately followed by oral prednisone (0.6 mg/kg body weight), with dose reduced 19 weeks later and switched to cyclosporine A (4 mg/kg body weight). Kidney re-biopsy, at that time, showed a decrease in proportion of glomeruli affected with podocytopathy, but progression of interstitial lesions. After 23 weeks of therapy, partial remission of FSGS was attained and proteinuria dropped to 3.6 g/24 h. After 43 weeks, proteinuria decreased to 0.4 g/24 h and the serum creatinine concentration remained steady. CONCLUSIONS High-dose glucocorticoid therapy was effective in the initial treatment of COVID-19-related non-collapsing FSGS, but had no effect on interstitial changes. Introduction of cyclosporine A to the therapy contributed to remission of disease.