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Chemical Research in Toxicology Aug 2023Myeloperoxidase (MPO) is an important component of the human innate immune system and the main source of a strong oxidizing and chlorinating species, hypochlorous acid...
Myeloperoxidase (MPO) is an important component of the human innate immune system and the main source of a strong oxidizing and chlorinating species, hypochlorous acid (HOCl). Inadvertent, misplaced, or excessive generation of HOCl by MPO is associated with multiple human inflammatory diseases. Therefore, there is a considerable interest in the development of MPO inhibitors. Here, we report the synthesis and characterization of a boronobenzyl derivative of acetaminophen (AMBB), which can function as a proinhibitor of MPO and release acetaminophen, the inhibitor of chlorination cycle of MPO, in the presence of inflammatory oxidants, i.e., hydrogen peroxide, hypochlorous acid, or peroxynitrite. We demonstrate that the AMBB proinhibitor undergoes conversion to acetaminophen by all three oxidants, with the involvement of the primary phenolic product intermediate, with relatively long half-life at pH 7.4. The determined rate constants of the reaction of the AMBB proinhibitor with hydrogen peroxide, hypochlorous acid, or peroxynitrite are equal to 1.67, 1.6 × 10, and 1.0 × 10 M s, respectively. AMBB showed lower MPO inhibitory activity (IC > 0.3 mM) than acetaminophen (IC = 0.14 mM) toward MPO-dependent HOCl generation. Finally, based on the determined reaction kinetics and the observed inhibitory effects of two plasma components, uric acid and albumin, on the extent of AMBB oxidation by ONOO and HOCl, we conclude that ONOO is the most likely potential activator of AMBB in human plasma.
Topics: Humans; Oxidants; Acetaminophen; Hypochlorous Acid; Hydrogen Peroxide; Peroxidase; Peroxynitrous Acid; Oxidation-Reduction
PubMed: 37534491
DOI: 10.1021/acs.chemrestox.3c00140 -
Food Microbiology Aug 2024Oxidation-reduction potential (ORP) is commonly used as a rapid measurement of the antimicrobial potential of free chlorine during industrial fresh produce washing. The...
The influence of pH on the efficacy of oxidation-reduction potential (ORP) to predict chlorine disinfection of surrogate bacteria, Escherichia coli O157:H7 and Listeria monocytogenes in oxidant demand free conditions and fresh produce wash water.
Oxidation-reduction potential (ORP) is commonly used as a rapid measurement of the antimicrobial potential of free chlorine during industrial fresh produce washing. The current study tested the hypothesis that ORP can act as a "single variable" measurement of bacterial (vegetative and endospores) inactivation effectiveness with free chlorine irrespective of the water pH value. This situation has on occasion been assumed but never confirmed nor disproven. Chlorine-dosed pH 6.5 and 8.5 phosphate buffer solutions were inoculated with Escherichia coli (E. coli), Listeria innocua (L. innocua), or Bacillus subtilis (B. subtilis) endospores. ORP, free chlorine (FC), and log reduction were monitored after 5 s (for E. coli and L. innocua) and up to 30 min (for B. subtilis spores) of disinfection. Logistic and exponential models were developed to describe how bacteria reduction varied as a function of ORP at different pH levels. Validation tests were performed in phosphate buffered pH 6.5 and 8.5 cabbage wash water periodically dosed with FC, cabbage extract and a cocktail of Escherichia coli O157:H7 (E. coli O157:H7) and Listeria monocytogenes (L. monocytogenes). The built logistic and exponential models confirmed that at equal ORP values, the inactivation of the surrogate strains was not consistent across pH 6.5 and pH 8.5, with higher reductions at higher pH. This is the opposite of the well-known free chlorine-controlled bacterial inactivation, where the antibacterial effect is higher at lower pH. The validation test results indicated that in the cabbage wash water, the relationship between disinfection efficiency and ORP was consistent with the oxidant demand free systems. The study suggests that ORP cannot serve as a reliable single variable measurement to predict bacterial disinfection in buffered systems. When using ORP to monitor and control the antibacterial effectiveness of the chlorinated wash water, it is crucial to take into account (and control) the pH.
Topics: Disinfection; Chlorine; Listeria monocytogenes; Food Contamination; Food Microbiology; Escherichia coli O157; Oxidants; Colony Count, Microbial; Food Handling; Chlorides; Oxidation-Reduction; Water; Anti-Bacterial Agents; Hydrogen-Ion Concentration; Phosphates; Listeria
PubMed: 38637078
DOI: 10.1016/j.fm.2024.104516 -
Ultrasonics Sonochemistry Oct 2023Antibiotics (ABX) residues frequently occurred in water and cow milk. This work aims to understand the kinetics and mechanisms of sonolytic degradation of four ABX, i.e....
Antibiotics (ABX) residues frequently occurred in water and cow milk. This work aims to understand the kinetics and mechanisms of sonolytic degradation of four ABX, i.e. ceftiofur hydrochloride (CEF), sulfamonomethoxine sodium (SMM), marbofloxacin (MAR), and oxytetracycline (OTC) in water and milk. In both water and milk, the sonolytic degradation of ABX follows pseudo-first order (PFO) kinetics well (R: 0.951-0.999), with significantly faster ABX degradation in water (PFO kinetics constants (k): 1.5 × 10-1.2 × 10 min) than in milk (k: 3.5 × 10-5.6 × 10 min). The k values for SMM degradation in water increased by 118% with ultrasonic frequency (40-120 kHz), 174% with ultrasonic frequency (80-500 kHz), 649% with ultrasonic power (73-259 W), 22% with bulk temperature (12-40℃), and by 68% with reaction volume (50-250 mL), respectively, in other things being equal. The relevant k values in milk increased by 326%, 231%, 122%, 10% as well as 82% with the above same effective factors, respectively. The oxidation by free radicals generated in situ dominates ABX degradation, and the hydrophobic CEF (54.0-971.7 nM min) and SMM (39.2-798.4 nM min) underwent faster degradation than the hydrophilic MAR (33.9-751.9 nM min) and OTC (33.8-545.3 nM min) in both water and milk. Adding an extra 0.5 mM HO accelerated SMM degradation by 19% in water and 33% in milk. After 130-150 min sonication of 100 mL of 2.0 mg L (6.62 μM) SMM in various milk with 500 kHz and 259 W, the residue concentrations (52.9-96.3 μg L) can meet the relevant maximum residue limit (100 μg L).
Topics: Animals; Anti-Bacterial Agents; Milk; Hydrogen Peroxide; Water; Kinetics; Water Pollutants, Chemical; Water Purification
PubMed: 37572426
DOI: 10.1016/j.ultsonch.2023.106518 -
International Journal of Molecular... Aug 2023Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In...
Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In this study, our aim was to elucidate the metabolic mechanisms underlying the protective effects of trehalose against hydrogen peroxide (HO)-induced oxidative stress in C2C12 myoblasts. Our results show that both trehalose treatment and pretreatment effectively alleviate the HO-induced decrease in cell viability, reduce intracellular reactive oxygen species (ROS), and attenuate lipid peroxidation. Furthermore, using NMR-based metabolomics analysis, we observed that trehalose treatment and pretreatment modulate the metabolic profile of myoblasts, specifically regulating oxidant metabolism and amino acid metabolism, contributing to their protective effects against oxidative stress. Importantly, our results reveal that trehalose treatment and pretreatment upregulate the expression levels of P62 and Nrf2 proteins, thereby activating the Nrf2-NQO1 axis and effectively reducing oxidative stress. These significant findings highlight the potential of trehalose supplementation as a promising and effective strategy for alleviating oxidative stress in skeletal muscle and provide valuable insights into its potential therapeutic applications.
Topics: Trehalose; Hydrogen Peroxide; NF-E2-Related Factor 2; Metabolomics; Oxidative Stress; Myoblasts
PubMed: 37686153
DOI: 10.3390/ijms241713346 -
Advanced Science (Weinheim,... Dec 2023Photocyclization is demonstrated as a powerful tool for building complicated polycyclic molecules. And efficient photocyclization is competent as an artful strategy to...
Photocyclization is demonstrated as a powerful tool for building complicated polycyclic molecules. And efficient photocyclization is competent as an artful strategy to develop photo-responsive smart materials. Herein, an efficient free radical-mediated photocyclization for triphenylphosphindole oxide (TPPIO) derivatives to generate tribenzophosphindole oxide (TBPIO) derivatives at ambient condition is reported. The reaction mechanism and substituent effect on photocyclization efficiency are thoroughly investigated. Additionally, photophysical and photochemical properties of TPPIO and TBPIO derivatives are measured for comparison and deeply deciphered by theoretical calculation. TPPIO derivatives own typical aggregation-induced emission feature but barely generate reactive oxygen species (ROS), while TBPIO derivatives experience aggregation-caused quenching but show efficient Type I ROS generation capacity. Further, in vitro experiments demonstrate that this photo-conversion can efficiently occur in situ in living cells to activate photodynamic therapy (PDT) effect to trigger lipid peroxidation with selective fluorescence "light up" in lipid droplet area under continuous irradiation. This work extends the optoelectronically and biologically interesting phosphindole oxide-containing π-conjugated systems through an efficient synthetic strategy, provides in-depth mechanistic descriptions in the aspects of reaction and property, and further presents their great potentials for photoactivated and self-reported PDT.
Topics: Humans; Reactive Oxygen Species; Lipid Peroxidation; Oxides; Self Report; Proteins
PubMed: 37870212
DOI: 10.1002/advs.202305516 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To explore the modulating effect of endogenous sulfur dioxide (SO) on the ba-lance of oxidation/reduction in the cecal-ligation-and-puncture-induced septic rat...
OBJECTIVE
To explore the modulating effect of endogenous sulfur dioxide (SO) on the ba-lance of oxidation/reduction in the cecal-ligation-and-puncture-induced septic rat myocardium.
METHODS
Forty male Sprague Dawley rats were randomized into control group, SOgroup, sepsis group and sepsis + SOgroup. The levels of procalcitonin (PCT), creatine kinase isoenzyme (CK-MB), cardiac troponin Ⅰ (cTn Ⅰ) and fatty acid binding protein (FABP) in plasma in each group of the rats were measured; The level of hydrogen peroxide (HO), level of nitric oxide (NO), activity of myeloperoxidase (MPO), activity of hydroxyl free radical (·OH) and level of malondialdehyde (MDA) in myocardial tissue were measured; Total antioxidant capacity (T-AOC), activity of catalase (CAT), level of cytochrome oxidase (CO), level of glutathione (GSH), level of glutathione oxidase (GSH-px) and activity of superoxide dismutase (SOD) in myocardial tissue were measured.
RESULTS
The level of PCT in plasma in the rats with sepsis increased from (0.93±0.26) μg/L to (2.45±0.52) μg/L ( < 0.01), and decreased to (1.58±0.36) μg/L after the intervention of sulfur dioxide donor ( < 0.01). In sepsis, the plasma CK-MB, cTn Ⅰ and FABP levels in the rats increased respectively from (14.46±6.48) μg/L, (151.25±30.14) ng/L and (2.72±0.65) μg/L to (23.72±7.72) μg/L, (272.78±52.70) ng/L and (5.22±1.01) μg/L ( all < 0.01), and decreased to (16.74±3.63) μg/L, (184.86±37.72) μg/L and (3.31±0.84) μg/L (all < 0.05) after the intervention of sulfur dioxide donor. The level of HO, level of NO, activity of MPO, activity of ·OH and level of MDA in myocardial tissue in the rats with sepsis increased respectively from (67.26±8.77) mmol/g, (38.39±6.93) μmol/g, (358.25±68.12) U/g, (648.42±93.69) U/ mg and (4.55±0.96) μmol/g to (111.45±17.35) mmol/g, (51.04±5.91) μmol/g, (465.88±76.76) U/g, (873.75±123.47) U/mg and (7.25±0.86) μmol/g (all < 0.01), and decreased respectively to (75.99±10.52) mmol/g, (39.39±7.80) μmol/g, (393.17±51.5) U/g, (710.54±106.33) U/mg and (5.16±0.65) μmol/g after the intervention of the sulfur dioxide donor (all < 0.05). The activity of T-AOC, activity of CAT, level of CO, level of GSH, level of GSH-px and activity of SOD in myocardial tissue in the rats with sepsis increased respectively from (2.07±0.37) U/mg, (169.25±36.86) U/g, (1.35±0.32) μmol/g, (103.51±16.62) μmol/g, (38.40±7.97) μmol/g and (38.50±8.30) U/mg to (1.42±0.39) U/mg, (98.44±26.56) U/g, (0.96±0.21) μmol/g, (68.05±7.35) μmol/ g, (23.83±5.04) μmol/g and (23.11±4.63) U/mg ( all < 0.01), and increased respectively to (1.83±0.37) U/mg, (146.14±31.63) U/g, (1.28±0.20) μmol/g, (92.10±11.84) μmol/g, (37.16±3.01) μmol/g and (37.29±2.62) U/mg ( all < 0.05) after the intervention of the sulfur dioxide donor.
CONCLUSION
Endogenous SO can protect rat myocardium in sepsis by modulating the ba-lance of oxidation and reduction.
Topics: Rats; Male; Animals; Oxidants; Sulfur Dioxide; Rats, Sprague-Dawley; Hydrogen Peroxide; Myocardium; Antioxidants; Superoxide Dismutase; Sepsis; Oxidative Stress; Malondialdehyde
PubMed: 37534635
DOI: 10.19723/j.issn.1671-167X.2023.04.002 -
Biomolecules Aug 2023The functioning of the immune and reproductive systems is crucial for the fitness and survival of species and is strongly influenced by the environment. To evaluate the...
The functioning of the immune and reproductive systems is crucial for the fitness and survival of species and is strongly influenced by the environment. To evaluate the effects of short-term heat stress (HS) on these systems, confirming and deepening previous studies, female sea urchin were exposed for 7 days to 17 °C, 23 and 28 °C. Several biomarkers were detected such as the ferric reducing power (FRAP), ABTS-based total antioxidant capacity (TAC-ABTS), nitric oxide metabolites (NO), total thiol levels (TTL), myeloperoxidase (MPO) and protease (PA) activities in the coelomic fluid (CF) and mitochondrial membrane potential (MMP), HO content and intracellular pH (pH) in eggs and coelomocytes, in which TAC-ABTS and reactive nitrogen species (RNS) were also analyzed. In the sea urchins exposed to HS, CF analysis showed a decrease in FRAP levels and an increase in TAC-ABTS, TTL, MPO and PA levels; in coelomocytes, RNS, MMP and HO content increased, whereas pH decreased; in eggs, increases in MMP, HO content and pH were found. In conclusion, short-term HS leads to changes in five out of the six CF biomarkers analyzed and functional alterations in the cells involved in either reproductive or immune activities.
Topics: Female; Animals; Paracentrotus; Hydrogen Peroxide; Antioxidants; Biomarkers; Iron; Nitric Oxide
PubMed: 37627280
DOI: 10.3390/biom13081216 -
Clinical Oral Investigations Sep 2023Method-dependent comparison of antimicrobial agents' efficacy against oral pathogens.
OBJECTIVES
Method-dependent comparison of antimicrobial agents' efficacy against oral pathogens.
MATERIALS AND METHODS
Several sodium hypochlorite solutions (NaOCl)-Perisolv, Carisolv and Dakin's solution-were equated with chlorhexidine (CHX) and hydrogen peroxide (HO) against ten oral micro-organisms related to caries and periodontitis using different minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) techniques. Agents were adjusted to the final 70 mmol/L concentration of active chlorine molecule.
RESULTS
Apart from HO and the amino acids of Perisolv, all the agents revealed an antimicrobial effect. Agar diffusion test ranked CHX (p < 0.05) as the most effective against all ten specimens, followed by the NaOCl of Perisolv and Dakin's solution. Correspondingly, in broth microdilution on agar, CHX was the most effective in eradicating micro-organisms at 0.03 mmol/L compared with 2.2 mmol/L of Dakin's solution. In contrast, the bactericidal concentration of Dakin's solution was the most effective at 0.2 mmol/L, (p < 0.001), followed by Perisolv (2.14 mmol/L), CHX (2.38 mmol/L) and Carisolv (3.33 mmol/L) after 5 and 10 min in broth dilution test. In live/dead analysis, 60-min exposure to a 2-fold concentration of agents resulted in two-log Aggregatibacter actinomycetemcomitans inhibition by CHX (35 mmol/L) whilst Streptococcus mutans was more susceptible, in 0.8 and 8.8 mmol/L, after 10 min to CHX and Dakin's respectively.
CONCLUSION
Replacement of CHX with tested hypochlorite agents showed evident potential and promoted rapid antimicrobial effect.
CLINICAL RELEVANCE
Effective antimicrobial agents are crucial in controlling pathogen-induced oral infections increasing clinical possibilities to combat oral biofilms. Additionally, CHX substitution with hypochlorite agents could eliminate CHX's adverse effects.
Topics: Chlorine; Hydrogen Peroxide; Agar; Hypochlorous Acid; Anti-Infective Agents; Halogens; Chlorhexidine; Sodium Hypochlorite
PubMed: 37606720
DOI: 10.1007/s00784-023-05190-0 -
Infection and Immunity Jul 2023Cystic echinococcosis (CE) is a disease caused by the infection of Echinococcus granulosus. We sought to investigate the effects of dihydroartemisinin (DHA) against CE...
Cystic echinococcosis (CE) is a disease caused by the infection of Echinococcus granulosus. We sought to investigate the effects of dihydroartemisinin (DHA) against CE under and conditions. Protoscoleces (PSCs) from were divided into control, DMSO, ABZ, DHA-L, DHA-M, and DHA-H groups. PSC viability after DHA treatment was determined based on the eosin dye exclusion test, alkaline phosphatase content detection, and ultrastructure observation. DNA oxidative damage inducer hydrogen peroxide (HO), reactive oxygen species (ROS) scavenger mannitol, and the DNA damage repair inhibitor velparib were used to explore the anti-CE mechanism of DHA. The anti-CE effects and CE-induced liver injury and oxidative stress of DHA at different doses (50, 100, and 200 mg/kg) were assessed in CE mice. DHA showed antiparasitic effects on CE in both and experiments. DHA could elevate the ROS level and induce oxidative DNA damage in PSCs, thereby destroying hydatid cysts. DHA could inhibit the growth of cysts in a dose-dependent manner and reduce the content of biochemical parameters associated with liver injury in CE mice. It also significantly reversed oxidative stress in CE mice, which was characterized as the decreased tumor necrosis factor alpha and HO content, as well as the increase of the ratio of glutathione/oxidized glutathione and total superoxide dismutase content. DHA showed antiparasitic effects. DNA damages induced by oxidative stress played important roles in this process.
Topics: Animals; Mice; Hydrogen Peroxide; Reactive Oxygen Species; Echinococcosis; Echinococcus granulosus; Antiparasitic Agents
PubMed: 37310215
DOI: 10.1128/iai.00470-22 -
Tissue Barriers Jul 2023Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc...
Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc oxide nanoparticles (ZnONPs) on cerebellar tissue and clarified the ameliorative role of Quercetin supplementation. Forty adult male albino rats were divided into control group (I), ZnONPs-exposed group (II), and ZnONPs and Quercetin group (III). Oxidative stress biomarkers (MDA & TOS), antioxidant biomarkers (SOD, GSH, GR, and TAC), serum interleukins (IL-1β, IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) were measured. Serum micro-RNA (miRNA): miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-3p expression levels were quantified by real-time quantitative polymerase-chain reaction (RT-QPCR). Cerebellar tissue sections were stained with Hematoxylin & Eosin and Silver stains and examined microscopically. Expression levels of Calbindin D28k, GFAP, and BAX proteins in cerebellar tissue were detected by immunohistochemistry. Quercetin supplementation lowered oxidative stress biomarkers levels and ameliorated the antioxidant parameters that were decreased by ZnONPs. No significant differences in GR activity were detected between the study groups. ZnONPs significantly increased serum IL-1β, IL-6, IL-8, and TNF-α which were improved with Quercetin. Serum miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-p expression levels showed significant increase in ZnONPs group, while no significant difference was observed between Quercetin-treated group and control group. ZnONPs markedly impaired cerebellar tissue structure with decreased levels of calbindin D28k, increased BAX and GFAP expression. Quercetin supplementation ameliorated cerebellar tissue apoptosis, gliosis and improved calbindin levels. In conclusion: Quercetin supplementation ameliorated cerebellar neurotoxicity induced by ZnONPs at cellular and molecular basis by different studied mechanisms. NPs: Nanoparticles, ROS: reactive oxygen species, ZnONPs: Zinc oxide nanoparticles, AgNPs: silver nanoparticles, BBB: blood-brain barrier, ncRNAs: Non-coding RNAs, miRNA: Micro RNA, DMSO: Dimethyl sulfoxide, LPO: lipid peroxidation, MDA: malondialdehyde, TBA: thiobarbituric acid, TOS: total oxidative status, ELISA: enzyme-linked immunosorbent assay, HO: hydrogen peroxide, SOD: superoxide dismutase, GR: glutathione reductase, TAC: total antioxidant capacity, IL-1: interleukin-1, TNF: tumor necrosis factor alpha, cDNA: complementary DNA, RT-QPCR: Real-time quantitative polymerase-chain reaction, ABC: Avidin biotin complex technique, DAB: 3', 3-diaminobenzidine, SPSS: Statistical Package for Social Sciences, ANOVA: One way analysis of variance, Tukey's HSD: Tukey's Honestly Significant Difference, GFAP: glial fiberillar acitic protein, iNOS: Inducible nitric oxide synthase, NO: nitric oxide, HO-1: heme oxygenase-1, Nrf2: nuclear factor erythroid 2-related factor 2, NF-B: nuclear factor-B, SCI: spinal cord injury, CB: Calbindin.
Topics: Rats; Male; Animals; Antioxidants; Quercetin; Zinc Oxide; Neuroprotective Agents; Tumor Necrosis Factor-alpha; bcl-2-Associated X Protein; Calbindin 1; Hydrogen Peroxide; Interleukin-6; Interleukin-8; Metal Nanoparticles; Silver; Superoxide Dismutase; Cerebellum; MicroRNAs; Biomarkers
PubMed: 35996208
DOI: 10.1080/21688370.2022.2115273