Browsing by Subject "Hydrogen peroxide"
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Item Color stability, Roughness, and Microhardness of Enamel and Composites Submitted to Staining/Bleaching Cycles(Elsevier, 2021-05) Al-Angari, Sarah S.; Eckert, George J.; Sabrah, Alaa H.A.; Biostatistics, School of Public HealthObjective: To compare the effect of two bleaching systems (bleaching gel and whitening strips) on the color change, roughness, and microhardness of enamel and two resin composites. Material and methods: Two cavities were prepared on bovine enamel specimens (n = 16) and restored with two composites: a nano-hybrid [Herculite Ultra (HU)] and a micro-hybrid composite [TPH Spectra (TS)]. Baseline color (CIE L*a*b*), roughness (μm), and microhardness (kgf/mm2) were measured using a spectrophotometer, optical profilometer, and Vickers microhardness (VHN) tester, respectively. The specimens were stained with coffee for 14 days, and randomized into two bleaching groups: gel and strips (n = 8), then submitted to a 10-day bleaching/staining test. Color, roughness, and microhardness were re-measured. The outcomes were analyzed using two-way ANOVA and Fisher's-PLSD test (α = 0.05). Results: Gel significantly improved the color (ΔE 4.9-8.3) and increased the roughness (Ra 0.04-0.08 μm) of all substrates (p < 0.0001) compared to strips. Enamel color was significantly improved (ΔE 5.4-8.3) compared to that of HU (ΔE 2.6-4.9) and TS (ΔE 2.0-4.9) with either gels or strips. TS roughness (0.03-0.08 μm) was significantly higher than that of enamel (0.01-0.05 μm) and HU (0.02-0.04 μm). Enamel had significantly reduced microhardness compared to HU (p = 0.0144). Conclusion: Gels produced the greatest color improvement and roughness compared to strips. Enamel had significant color improvement but had the greatest decrease in microhardness. Clinical significance: There was unacceptable color change between enamel and the composites after the combined cyclic effects of staining and bleaching.Item Importance of Per2 in cardiac mitochondrial protection during stress(Springer Nature, 2024-01-14) Bhaskara, Meghana; Anjorin, Olufisayo; Yoniles, Arris; Liu, Jianyun; Wang, Meijing; Surgery, School of MedicineDuring myocardial injury, inflammatory mediators and oxidative stress significantly increase to impair cardiac mitochondria. Emerging evidence has highlighted interplays between circadian protein-period 2 (Per2) and mitochondrial metabolism. However, besides circadian rhythm regulation, the direct role of Per2 in mitochondrial performance particularly following acute stress, remains unknown. In this study, we aim to determine the importance of Per2 protein's regulatory role in mitochondrial function following exposure to inflammatory cytokine TNFα and oxidative stressor H2O2 in human cardiomyocytes. Global warm ischemia (37 °C) significantly impaired complex I activity with concurrently reduced mitochondrial Per2 in adult mouse hearts. TNFα or H2O2 decreased Per2 protein levels and damaged mitochondrial respiratory function in adult mouse cardiomyocytes. Next, mitochondrial membrane potential ([Formula: see text] M) using JC-1 fluorescence probe and mitochondrial respiration capacity via Seahorse Cell Mito Stress Test were then detected in Per2 or control siRNA transfected AC16 Human Cardiomyocytes (HCM) that were subjected to 2 h-treatment of TNFα (100 ng/ml) or H2O2 (100 μM). After 4 h-treatment, cell death was also measured using Annexin V and propidium iodide apoptosis kit through flow cytometry. We found that knockdown of Per2 enhanced TNFα-induced cell death and TNFα- or H2O2-disrupted [Formula: see text]M, as well as TNFα- or H2O2-impaired mitochondrial respiration function. In conclusion, Per2 knockdown increases likelihood of cell death and mitochondrial dysfunction in human cardiomyocytes exposed to either TNFα or H2O2, supporting the protective role of Per2 in HCM during stress with a focus on mitochondrial function.Item KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine(American Physiological Society, 2016-03-15) Goodwill, Adam G.; Fu, Lijuan; Noblet, Jillian N.; Casalini, Eli D.; Sassoon, Daniel; Berwick, Zachary C.; Kassab, Ghassan S.; Tune, Johnathan D.; Dick, Gregory M.; Department of Cellular & Integrative Physiology, IU School of MedicineHydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli.Item Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase(Elsevier, 2017-11-20) Olson, Kenneth R.; Gao, Yan; Arif, Faihaan; Arora, Kanika; Patel, Shivali; DeLeon, Eric. R.; Sutton, Thomas R.; Feelisch, Martin; Cortese-Krott, Miriam M.; Straub, Karl D.; Cellular and Integrative Physiology, School of MedicineReactive sulfur species (RSS) such as H2S, HS•, H2Sn, (n = 2–7) and HS2•- are chemically similar to H2O and the reactive oxygen species (ROS) HO•, H2O2, O2•- and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that “antioxidant” enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1 μM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380 μM H2S. H2S concentrations > 750 μM inhibited SOD oxidation (IC50 = 1.25 mM) with complete inhibition when H2S > 1.75 mM. Polysulfides were not metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to form polysulfides, but did not metabolize polysulfides indicating common attributes of these SODs. These experiments suggest that, unlike the well-known SOD-mediated dismutation of two O2•- to form H2O2 and O2, SOD catalyzes a reaction using H2S and O2 to form persulfide. These can then combine in various ways to form polysulfides and sulfur oxides. It is also possible that H2S (or polysulfides) interact/react with SOD cysteines to affect catalytic activity or to directly contribute to sulfide metabolism. Our studies suggest that H2S metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to regulate RSS and along with catalase may continue to do so in contemporary organisms., • Polysulfides are reactive sulfide species (RSS) and are similar to reactive oxygen species (ROS). • RSS may be the antecedent of redox regulatory and stress-related modalities. • RSS likely persist in modern-day organisms and are regulated by SOD.Item Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage(PNAS, 2014-09-16) Cleaver, James E.; Brennan-Minnella, Angela M.; Swanson, Raymond A.; Fong, Ka-wing; Chen, Junjie; Chou, Kai-ming; Chen, Yih-wen; Revet, Ingrid; Bezrookove, Vladimir; Department of Pharmacology and Toxicology, IU School of MedicineCockayne syndrome (CS) is a human DNA repair-deficient disease that involves transcription coupled repair (TCR), in which three gene products, Cockayne syndrome A (CSA), Cockayne syndrome B (CSB), and ultraviolet stimulated scaffold protein A (UVSSA) cooperate in relieving RNA polymerase II arrest at damaged sites to permit repair of the template strand. Mutation of any of these three genes results in cells with increased sensitivity to UV light and defective TCR. Mutations in CSA or CSB are associated with severe neurological disease but mutations in UVSSA are for the most part only associated with increased photosensitivity. This difference raises questions about the relevance of TCR to neurological disease in CS. We find that CSB-mutated cells, but not UVSSA-deficient cells, have increased levels of intramitochondrial reactive oxygen species (ROS), especially when mitochondrial complex I is inhibited by rotenone. Increased ROS would result in oxidative damage to mitochondrial proteins, lipids, and DNA. CSB appears to behave as an electron scavenger in the mitochondria whose absence leads to increased oxidative stress. Mitochondrial ROS, however, did not cause detectable nuclear DNA damage even when base excision repair was blocked by an inhibitor of polyADP ribose polymerase. Neurodegeneration in Cockayne syndrome may therefore be associated with ROS-induced damage in the mitochondria, independent of nuclear TCR. An implication of our present results is that mitochondrial dysfunction involving ROS has a major impact on CS-B pathology, whereas nuclear TCR may have a minimal role.Item A novel approach to aesthetically treat arrested caries lesions(2017) Alangari, Sarah Sultan A.; Hara, Anderson T.; Lippert, Frank; Platt, Jeffrey A.; González-Cabezas, Carlos; Li, YimingIn this thesis, we proposed and investigated the efficacy and safety of dental bleaching as a non-invasive aesthetic treatment option for stained arrested caries lesions (s-ACLs). Chapter 1 reports the suitability of this approach in extracted human teeth, as well as in a selected clinical case. Visual improvement in the color lighteness of the s-ACLs was observed and reported in photographs. In order to systematically study the impact of dental bleaching on the s-ACLs, we developed in vitro models simulating the development of metallic and non-metallic s-ACLs (Chapter 2). Human dental specimens were submitted to incipient caries-like lesion formation, followed by a 5-day cycling protocol based on remineralization and staining episodes. The created lesions were then bleached (simulating in-office/40% hydrogen peroxide). Color change was measured spectrophotometrically at baseline, after lesion creation, staining/remineralization cycling and bleaching; while mineral loss and lesion depth were quantified by transversal microradiography after staining/remineralization cycling. Metallic s-ACLs were darker, more remineralized and more difficult to bleach, compared to the non-metallic ones (p<0.05). In Chapter 3, we tested the efficacy and safety of different dental bleaching systems (simulating at-home/15% carbamide peroxide and in-office/40% hydrogen peroxide) using the in vitro models previously developed. Similar methods and outcomes were used, with the addition of demineralization after bleaching to simulate and test changes in caries susceptibility. At-home bleaching showed greater efficacy in color improvement compared to in-office (p<0.05), but also increased susceptibility to further demineralization (p<0.05), regardless of the type of stain. Overall, bleached non-metallic s-ACLs were more susceptible to demineralization compared to metallic ones (p<0.05). Within the limited laboratory testing conditions, we concluded that dental bleaching can improve the aesthetics of s-ACLs, with efficacy being dependent on the nature of the stain. At-home bleaching presented greater efficacy, but also raised some potential safety concerns, which should be further investigated in clinical conditions. In-office bleaching protocol showed to be an effective and safe procedure for the aesthetic treatment of stained arrested caries lesions.Item Occludin Content Modulates Hydrogen Peroxide–Induced Increase in Renal Epithelial Paracellular Permeability(Wiley, 2016-03) Janosevic, Danielle; Axis, Josephine; Bacallao, Robert L.; Amsler, Kurt; Department of Medicine, IU School of MedicineThe ability of hydrogen peroxide (H2O2) to increase paracellular permeability of renal epithelial cell monolayers was examined and the role of occludin in this regulation was investigated. H2O2 treatment increased the paracellular movement of calcein, a marker for the leak pathway permeability, across monolayers of two renal epithelial cell lines, MDCK and LLC-PK1, in a concentration-dependent manner. At the same concentrations, H2O2 did not alter transepithelial resistance (TER) nor increase cell death. The magnitude of the H2O2-induced increase in leak pathway permeability was inversely related to cellular occludin protein content. H2O2 treatment did not produce any major change in total cellular content or Triton X-100-soluble or -insoluble fraction content of occludin protein. Occludin protein staining at the tight junction region was diminished following H2O2 treatment. The most dramatic effect of H2O2 was on the dynamic mobility of GFP-occludin into the tight junction region. H2O2 treatment slowed lateral movement of GFP-occludin into the tight junction region but not on the apical membrane. Further, removal of the cytoplasmic C-terminal region of occludin protein eliminated the effect of H2O2 on GFP-occludin lateral movement into the tight junction region. An increase in the mobile fraction of GFP-occludin was associated with a loss of response to H2O2. These data indicate that the H2O2-induced increase in renal epithelial cell paracellular permeability is mediated, at least in part, through occludin protein, possibly through a slowing of the rate of occludin movement into the tight junction region.Item Personalized Genome-Scale Metabolic Models Identify Targets of Redox Metabolism in Radiation-Resistant Tumors(Cell Press, 2021) Lewis, Joshua E.; Forshaw, Tom E.; Boothman, David A.; Furdui, Cristina M.; Kemp, Melissa L.; Biochemistry and Molecular Biology, School of MedicineRedox cofactor production is integral toward antioxidant generation, clearance of reactive oxygen species, and overall tumor response to ionizing radiation treatment. To identify systems-level alterations in redox metabolism that confer resistance to radiation therapy, we developed a bioinformatics pipeline for integrating multi-omics data into personalized genome-scale flux balance analysis models of 716 radiation-sensitive and 199 radiation-resistant tumors. These models collectively predicted that radiation-resistant tumors reroute metabolic flux to increase mitochondrial NADPH stores and reactive oxygen species (ROS) scavenging. Simulated genome-wide knockout screens agreed with experimental siRNA gene knockdowns in matched radiation-sensitive and radiation-resistant cancer cell lines, revealing gene targets involved in mitochondrial NADPH production, central carbon metabolism, and folate metabolism that allow for selective inhibition of glutathione production and H2O2 clearance in radiation-resistant cancers. This systems approach represents a significant advancement in developing quantitative genome-scale models of redox metabolism and identifying personalized metabolic targets for improving radiation sensitivity in individual cancer patients.Item Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity(Springer Nature, 2018-07-31) Liu, Yuan; Naha, Pratap C.; Hwang, Geelsu; Kim, Dongyeop; Huang, Yue; Simon-Soro, Aurea; Jung, Hoi-In; Ren, Zhi; Li, Yong; Gubara, Sarah; Alawi, Faizan; Zero, Domenick; Hara, Anderson T.; Cormode, David P.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryFerumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.