Permeation mechanisms of hydrogen peroxide and water through Plasma Membrane Intrinsic Protein aquaporins.

Hydrogen peroxide (H2O2) transport by aquaporins (AQP) is a critical feature for cellular redox signaling. However, the H2O2 permeation mechanism through these channels remains poorly understood. Through functional assays, two Plasma membrane Intrinsic Protein (PIP) AQP from Medicago truncatula, MtPIP2;2 and MtPIP2;3 have been identified as pH-gated channels capable of facilitating the permeation of both water (H2O) and H2O2. Employing a combination of unbiased and enhanced sampling molecular dynamics simulations, we investigated the key barriers and translocation mechanisms governing H2O2 permeation through these AQP in both open and closed conformational states. Our findings reveal that both H2O and H2O2 encounter their primary permeation barrier within the selectivity filter (SF) region of MtPIP2;3. In addition to the SF barrier, a second energetic barrier at the NPA (asparagine-proline-alanine) region that is more restrictive for the passage of H2O2 than for H2O, was found. This behavior can be attributed to a dissimilar geometric arrangement and hydrogen bonding profile between both molecules in this area. Collectively, these findings suggest mechanistic heterogeneity in H2O and H2O2 permeation through PIPs.

Heme metabolism in Strigomonas culicis: Implications of H2O2 resistance induction and symbiont elimination.

Monoxenous trypanosomatid Strigomonas culicis harbors an endosymbiotic bacterium, which enables the protozoa to survive without heme supplementation. The impact of H2O2 resistance and symbiont elimination on intracellular heme and Fe2+ availability was analyzed through a comparison of WT strain with both WT H2O2-resistant (WTR) and aposymbiotic (Apo) protozoa. The relative quantification of the heme biosynthetic pathway through label-free parallel reaction monitoring targeted mass spectrometry revealed that H2O2 resistance does not influence the abundance of tryptic peptides. However, the Apo strain showed increased coproporphyrinogen III oxidase and ferrochelatase levels. A putative ferrous iron transporter, homologous to LIT1 and TcIT from Leishmania major and Trypanosoma cruzi, was identified for the first time. Label-free parallel reaction monitoring targeted mass spectrometry also showed that S. culicis Iron Transporter (ScIT) increased 1.6- and 16.4-fold in WTR and Apo strains compared to WT. Accordingly, antibody-mediated blockage of ScIT decreased by 28.0% and 40.0% intracellular Fe2+concentration in both WTR and Apo strains, whereas no effect was detected in WT. In a heme-depleted medium, adding 10 µM hemin decreased ScIT transcript levels in Apo, whereas 10 µM PPIX, the substrate of ferrochelatase, increased intracellular Fe2+ concentration and ferric iron reduction. Overall, the data suggest mechanisms dependent on de novo heme synthesis (and its substrates) in the Apo strain to overcome reduced heme availability. Given the importance of heme and Fe2+ as cofactors in metabolic pathways, including oxidative phosphorylation and antioxidant systems, this study provides novel mechanistic insights associated with H2O2 resistance in S. culicis.

Efficacy of a buccal and lingual at-home bleaching protocol-A randomized, split-mouth, single-blind controlled trial.

OBJECTIVE: To compare the color change, the risk and intensity of tooth sensitivity (TS), and gingival irritation (GI) of at-home bleaching applied on the buccal surface only or the buccal and lingual surfaces. MATERIALS AND METHODS: Sixty patients with canines A2 or darker were selected and their superior arches were randomized in two groups: at-home bleaching on the buccal-only or on the buccal and lingual surfaces, with 7.5% hydrogen peroxide, for 1 h daily/2 weeks. The color change was evaluated at baseline, 7, 14 days, and 1 month after bleaching using shade guides scales (ΔSGU) and a spectrophotometer (ΔEAB, ΔE00, and ΔWID). Risk and intensity of TS and GI were recorded daily using visual analogic scale (0-10). Patient satisfaction was evaluated with the orofacial esthetics. Paired t-test, McNemar's, and Wilcoxon signed-rank test were used for data analysis (α = 5%). RESULTS: Neither the color change nor the risk/intensity of TS was statistically different between groups (p > 0.05). Patient satisfaction increased after bleaching for both groups (p < 0.05). CONCLUSION: The addition of one contact surface does not result in an increased whitening degree compared to bleaching applied solely on the buccal surface. CLINICAL SIGNIFICANCE: Understanding the influence of surfaces interacting with the bleaching agent is crucial for comprehending the bleaching mechanism and avoiding unnecessary material expenses. Notably, employing the buccal-only technique is sufficient to achieve the desired efficacy.

Peróxido de carbamida 37% no clareamento dentário e sua atuação na efetividade clareadora e eliminação de sensibilidade: relato de caso / The usage of 37% carbamide peroxide in tooth bleaching and its effect on bleaching effectiveness and elimination of sensitivity: a case report / Peróxido de carbamida al 37% en el blanqueamiento dental y su efecto sobre la eficacia del blanqueamiento y la eliminación de la sensibilidad: informe de un caso

Introdução:A sensibilidade dentária é o efeito adverso mais comum relacionado ao clareamento dentário. Na técnica de consultório, o peróxido de carbamida a 37%, surgiu como possibilidade de clarear e não causar sensibilidade.Objetivo:trata-se deum relato de caso, que avaliou a eficácia (mudança de cor) e a presença ou não de sensibilidade dentária quando se fezo uso de um produto àbase de peróxido de hidrogênio a35% e outro de peróxido de carbamida a 37%, na técnica de clareamento dentário de consultório.Relato de caso:Paciente de25 anos, sexo masculino, submetido a estudo de boca dividida, onde no hemiarco esquerdo foi aplicado peróxido de hidrogênio a 35% e no hemiarco direito, peróxido de carbamida a 37%. Foram feitas 3 sessões, sendo Peróxido de Carbamidacom aplicação única de 45 minutos, e Peróxido de Hidrogêniocom 3 aplicações de 15 minutos, em seu respectivo lado de aplicação e intervalo de sete dias entre cada sessão. Os valores de sensibilidade foram analisados antes e depois de cada sessão por meio da escala visual analógica de dor, e a alteração de cor foi avaliada através da Escala Vita, analisando incisivos e caninos superiores, antes de cada sessão.Conclusões:O clareamento dental com o Peróxido de Hidrogênio apresentou melhor eficácia clareadora e o Peróxido de Carbamida apresentou ausência de sensibilidade durante o procedimento clareador. Sugerem-se mais estudos do tipo ensaio clínico, com o Peróxido de Carbamida, para que se possa, com uma amostra maior de pacientes, verificar suas vantagens no quesito sensibilidade, bem como sua efetividade clareadora (AU).

Introduction:Tooth sensitivity is the most common adverse effect related to tooth bleaching. In the in-office technique, 37% carbamide peroxide has emerged as a way of tooth bleaching which does not cause sensitivity.Objective:This paper consists of a case report that evaluated the efficacy (color change) and the presence or absence of tooth sensitivity when using a product based on 35% hydrogen peroxide and another product based on 37% carbamide peroxide in the in-office tooth bleaching technique.Case report:A 25-year-old male patient underwent a split-mouth study in which 35% hydrogen peroxide was applied to the left hemi-arch and 37% carbamide peroxide to the right hemi-arch. Three sessions were carried out, carbamide peroxide with a single 45-minute application, and hydrogen peroxide with three 15-minute applications, on their respective application side and with a seven-day interval between each session. Sensitivity values were analyzed before and after each session using the visual analogue pain scale, and color change was assessed using the Vita Scale, analyzing upper incisors andcanines before each session. Conclusions:Teeth bleaching with hydrogen peroxide showed better bleaching efficacy and carbamide peroxide showed no sensitivity during the bleaching procedure. Further clinical trials with carbamide peroxide are suggested inorder to verify, with a larger sample of patients, its advantages in terms of sensitivity, as well asits bleaching effectiveness (AU).

Introducción: La sensibilidad de la dentina es el efecto adverso más común relacionado con el blanqueamiento dental. En la técnica en clínica, el peróxido de carbamida al 37% ha surgido como una posibilidad de blanqueamiento sin causar sensibilidad.Objetivo: Se tratade un informe de caso que evaluó la eficacia (cambio de color) y la presencia o ausencia de sensibilidad de la denina al utilizar un producto a base de peróxido de hidrógeno al 35% y otro a base de peróxido de carbamida al 37% en la técnica de blanqueamiento dental en clínica.Informe de caso:Un paciente del sexo maculino de 25 años fue sometido a un estudio de boca dividida en el que se aplicó peróxido de hidrógeno al 35% en la hemiarcada izquierda y peróxido de carbamida al 37% en la hemiarcada derecha.Se realizaron tres sesiones, la peróxido de carbamida con una única aplicación de 45 minutos, y la peróxido de hidrógeno con tres aplicaciones de 15 minutos, en sus respectivos lados de aplicación y con un intervalo de siete días entre cada sesión. Se analizaron los valores de sensibilidad antes y después de cada sesión mediante la escala analógica visual del dolor, y se evaluó el cambio de color mediante la Escala Vita, analizando los incisivos superiores y los caninos antes de cada sesión. Conclusiones: El blanqueamiento dental con peróxido de hidrógeno demostró una mayor eficacia blanqueadora y el peróxido de carbamida no manifestó sensibilidad durante el procedimiento de blanqueamiento. Se sugiere realizar más ensayos clínicos con peróxido de carbamidaparapoder utilizar una muestra mayor de pacientes y verificar sus ventajas en términos de sensibilidad, así como su eficacia blanqueadora (AU).

Embryotoxicity and teratogenesis of orthodontic acrylic resin in zebrafish.

Objectives: This study investigated the in vivo embryotoxicity, teratogenic potential, and additional effects of orthodontic acrylic resin as well as its components, utilizing zebrafish as a model organism. The research focused on morphological, cardiac, behavioral, and cognitive evaluations that were performed on embryos and larval-stage animals subjected to chronic exposure. Materials and methods: Embryo and larval-stage zebrafish were categorized into five experimental groups, which were further subdivided into five subgroups. These subgroups included three specific doses for each tested substance, a control with the vehicle (0.1 % dimethyl sulfoxide in water), and an absolute control (water). Assessments were performed on day 5 post-fertilization, which included morphological, cardiac, behavioral, and cognitive evaluations. All experiments had a sample size of ten animals and were performed in triplicate. Survival and hatching rates were analyzed using the Kaplan-Meier test, while other measurements were assessed using one-way analysis of variance (ANOVA), followed by the Tukey post hoc test. Results: Statistically significant differences were observed between the control and treatment groups across all the tested substances for heart rate, cognitive responsiveness, and cellular apoptosis. However, survival, hatching rate, and other parameters exhibited no significant variation, except for the highest dose in the dibutyl phthalate group, which demonstrated a notable difference in survival. Conclusions: Chronic exposure to acrylic resin and its components may be associated with decreased cognitive ability and cardiac rhythm, as well as an increase in the level of cellular apoptosis in zebrafish.

The Structural Biology of Catalase Evolution.

Catalases are essential enzymes for removal of hydrogen peroxide, enabling aerobic and anaerobic metabolism in an oxygenated atmosphere. Monofunctional heme catalases, catalase-peroxidases, and manganese catalases, evolved independently more than two billion years ago, constituting a classic example of convergent evolution. Herein, the diversity of catalase sequences is analyzed through sequence similarity networks, providing the context for sequence distribution of major catalase families, and showing that many divergent catalase families remain to be experimentally studied.

Effects of experimental in-office bleaching gels incorporated with co-doped titanium dioxide nanoparticles on dental enamel physical properties.

To evaluate the physical properties of enamel submitted to hydrogen peroxide (HP) incorporated with titanium dioxide nanoparticles (NP) co-doped with nitrogen and fluorine and irradiated with violet LED light (LT). Enamel-dentin disks were randomly allocated (T0) into groups, according to HP (HP6, HP15, or HP35) and NP (no NP, 5NP, or 10NP) concentrations, and irradiated or not with LT. A negative control (NC) group was set. After three bleaching sessions (T1, T2, and T3), specimens were stored in saliva for 14 days (T4). Enamel surface microhardness number (KHN), surface roughness (Ra), cross-sectional microhardness (ΔS), energy-dispersive spectroscopy (EDS), scanning electron (SEM), and polarized light (PLM) microscopies were performed. Surface KHN was significantly influenced by NP over time, independently of LT irradiation. At T3 and T4, gels with 5NP and 10NP exhibited no KHN differences compared to NC and baseline values, which were not observed under the absence of NP. NP incorporation did not statistically interfere with the ΔS and Ra. PLM images exhibited surface/subsurface darkening areas suggestive of demineralizing regions. SEM demonstrated some intraprismatic affection in the groups without NP. EDS reported a higher enamel calcium to phosphorus ratio following 10NP gels applications. Gels with NP maintained the enamel surface microhardness levels and seemed to control surface morphology, upholding the mineral content. None of the proposed experimental protocols have negatively influenced the enamel surface roughness and the cross-sectional microhardness.

Assessment of the effect of experimental gel of pregabalin associated with 35% hydrogen peroxide bleaching on bovine dental enamel: an in vitro study.

To assess the effect of bleaching with gel of pregabalin associated with 35% hydrogen peroxide on the mechanical and chemical properties and ultramorphology of dental enamel. Thirty-six (36) specimens of bovine dental incisors were obtained and divided into three groups (n = 12), namely: CG = bleaching with 35% hydrogen peroxide; KFG = bleaching with 5% potassium nitrate and 2% sodium fluoride gel + 35% hydrogen peroxide; and PGG = bleaching with experimental gel of pregabalin + 35% hydrogen peroxide. The specimens were assessed with respect to Knoop microhardness, surface roughness, and colour change, before and after bleaching. They were also assessed using scanning electron microscopy and energy-dispersive spectroscopy after treatments. All groups exhibited an increase in surface roughness and a reduction in Knoop microhardness after the protocols. There was colour change in all groups, with no difference between them. In addition, there were changes in enamel morphology and non-significant loss of calcium and phosphorus. The experimental gel of pregabalin did not influence the action of 35% hydrogen peroxide, yielding results similar to those of the other groups assessed in all the parameters. Therefore, the gel of pregabalin can be an alternative for topical application on the surfaces of the teeth in association with bleaching treatments.

Clinical comparison of whitening efficacy and tooth sensitivity of different concentrations of hydrogen peroxide photoactivated with violet or blue LEDs.

This study evaluated the photoactivation of hydrogen peroxide gels at different concentrations using blue or violet LED in terms of whitening efficacy and tooth sensitivity. Forty patients were randomly divided into 4 groups: HP6V (violet LED and 6% hydrogen peroxide), HP6B (blue LED and 6% hydrogen peroxide), HP35V (violet LED and 35% hydrogen peroxide), and HP35B (blue LED and 35% hydrogen peroxide). The L*, a* and b* values were measured before, 1 week and 3 months after treatment, and the ΔE and ΔWID values were calculated. Tooth sensitivity was measured using a visual analogue scale (VAS) before, immediately after, and 24 h after bleaching. The ΔE, ΔWID and bleaching sensitivity values were subjected to the ANOVA test and Bonferroni post-test. HP35V and HP35B showed higher whitening efficacy than HP6VL, while HP6V did not show statistical differences compared to the other groups. Regarding bleaching-related sensitivity, the HP6V and HP6B groups presented the lowest values when compared to HP35V and HP35B. HP6V showed whitening efficacy comparable to HP35V and HP35B but with reduced tooth sensitivity. TRIAL REGISTRATION NUMBER: NCT06165458; registration date: 12/09/2023.

The decomposition rate and bleaching efficacy of in-office bleaching gels with different pHs: a randomized controlled trial.

BACKGROUND: To evaluate the decomposition rate of active hydrogen peroxide (HP) and bleaching efficacy during in-office bleaching using high-concentration HP gels with different pHs. METHOD: A randomized, parallel, double-blind controlled trial was conducted with 40 volunteers randomized into four groups (pH 5.4; pH 7.0; pH 7.7, and pH 8.0). During the first session in-office bleaching, approximately 0.01 g of the gel was collected and titrated with potassium permanganate to obtain the concentration of active HP and pH values were measured using an electrode. Bleaching efficacy was assessed using a spectrophotometer [∆Eab, ∆E00, and WID], Vita Classical and Vita Bleachedguide scales [∆SGU]. The decomposition rate of HP concentration and pH values change were calculated using ANOVA one-way. The bleaching efficacy was assessed using two-way repeated measures ANOVA. Tukey's test was applied as a post-hoc test (p < 0.05). RESULTS: All gels experienced decreasing HP concentration over time. pH 5.4 gel showed greatest reduction after 50 min (p < 0.001). pH 8.0 and 7.7 gels remained stable; pH 5.4 remained acidic, while pH 7.0 turned acidic (p < 0.001). No significant difference in bleaching degree was observed among gels. They all showed a similar and clinically important color change after two clinical sessions, remained stable 1-month post-treatment (p > 0.05). CONCLUSIONS: All bleaching gels kept at least 70% of their HP content after 50 min, suggesting that there is a surplus of HP. They provided similar whitening efficacy 1-month after bleaching. PRACTICAL IMPLICATIONS: It is possible that lower HP concentrations may be equally effective in achieving desired results while reducing the potential for side effects. CLINICAL TRIAL REGISTRY NAME: RBR-35q7s3v.

Effect of a brush tip on in-office bleaching gels in an attachable syringe: Hydrogen peroxide penetration, bleaching efficacy and amount of gel expended.

OBJECTIVE: Evaluate the penetration of hydrogen peroxide (HP) into the pulp chamber, bleaching efficacy (BE) and amount of gel expended during in-office bleaching using an applicator brush tip and conventional tip from different commercial brands. MATERIALS AND METHODS: 104 human premolars were randomly distributed into thirteen groups (n = 8) according to the commercial brand: DSP White Clinic 35 % Calcium (DW), Nano White 35 % (NW), Total Blanc One-Step 35 % (TS), Whiteness HP Blue 35 % (WB), Potenza Bianco Pro SS 38 % (PB), Opalescence XTra Boost 40 % (OB), no bleaching (negative control), and application method: applicator brush tip and conventional tip for all groups. Initial HP concentration (%) was determined via titration and pH was measured with digital pH meter. Concentration (µg/mL) of HP into the pulp chamber was measured using UV-Vis spectrophotometry, the BE (ΔE*ab, ΔE00 and ΔWID) was evaluated with a digital spectrophotometer, and the amount of gel expended was evaluated using a precision analytical digital balance. Statistical analysis included two-way ANOVA, Tukey's, and Dunnett's test. Comparison between HP into the pulp chamber vs BE was performed with Person's correlation (α = 0.05). RESULTS: Brush tip demonstrated a low amount of HP in the pulp chamber compared to the conventional method for all bleaching gels (p < 0.0003), as well as lower amount of gel expended (p < 0.002). The brush tip did not result in a significant difference in BE compared to the conventional (p > 0.05). No correlations were found between both factors (p > 0.05). CONCLUSION: Brush tip showed lower penetration of HP in the pulp chamber and a reduced volume of spent gel when compared to the conventional tip, for all commercial brands. CLINICAL RELEVANCE: Brush tip is recommended for bleaching gels in an attachable syringe due to its ability to reduce the penetration of HP into the pulp chamber and minimize the amount of bleaching gel used.

Whitening toothpastes with hydrogen peroxide concentrations vs. at-home bleaching.

OBJECTIVES: To evaluate the effect of whitening toothpastes with different hydrogen peroxide (HP) concentrations on HP permeability, color change, and physicochemical properties, compared to at-home bleaching treatment. MATERIALS AND METHODS: Forty-nine premolars were randomized into seven groups (n = 7): untreated (control); at-home bleaching with 10% carbamide peroxide gel (AH; 10% CP) with 14 and 28 applications of 180 min each (AH [14 × 180 min] and AH [28 × 180 min]); three whitening toothpastes (3% HP; 4% HP and 5% HP) and 10% CP brushed 28 times for 90 s each (TB [28 × 90 s]). HP permeability was measured using a UV-VIS spectrophotometer and color change by a digital spectrophotometer (ΔEab, ΔE00, and ΔWID). Initial concentration, pH, and viscosity were measured through titration, digital pH meter, and rheometer, respectively. Statistical analysis included one-way ANOVA, Tukey's test, and Dunnett's test (α = 0.05). RESULTS: 4% HP group showed acidic pH, the lowest viscosity and the highest HP concentration into the pulp chamber (p < 0.05). The 10% CP groups had lower HP in the pulp chamber and greater color change than other groups (p < 0.05), except the 5% HP group in ΔEab and ΔE00. For ΔWID, the 10% CP AH groups showed greater whitening than other groups (p < 0.05). CONCLUSIONS: Whitening toothpaste with up to 5% HP resulted in higher HP permeability and less color change compared to 10% CP. Higher HP commercial concentrations in toothpaste increased whitening effect; however, acidic pH toothpastes exhibited greater HP permeability. CLINICAL RELEVANCE: Whitening toothpastes with high hydrogen peroxide concentrations were less effective than at-home bleaching, resulting in less color change and greater permeability of hydrogen peroxide, potentially increasing the risk of tooth sensitivity.

Can carbamide peroxide be as effective as hydrogen peroxide for in-office tooth bleaching and cause less sensitivity? A systematic review.

This study aimed to answer the question through a systematic review: Can carbamide peroxide be as effective as hydrogen peroxide and cause less in-office bleaching sensitivity? A literature survey was performed in PubMed/MEDLINE, Embase, Scopus, ISI Web of Science, and gray literature. Primary clinical trials that compared the efficacy or the in-office bleaching sensitivity between carbamide and hydrogen peroxides were included. The risk of bias was evaluated using the RoB2. The certainty of the evidence was assessed using the GRADE approach. DPI training significantly improved the mean scores of the dental undergraduates from 7.53 in the pre-DPI-training test to 9.01 in the post-DPI-training test (p < 0.001). After 6 weeks, the mean scores decreased marginally to 8.87 in the retention test (p = 0.563). DPI training increased their confidence level from 5.68 pre-DPI training to 7.09 post-DPI training. The limited evidence suggests that the 37% carbamide peroxide may be similarly effective to the 35% hydrogen peroxide for bleaching teeth in-office and causes less bleaching sensitivity. However, more well-designed split-mouth clinical trials are necessary to strengthen the evidence.

Nitrogen and Silicon Contribute to Wheat Defense's to Pyrenophora tritici-repentis, but in an Independent Manner.

Nitrogen (N) and silicon (Si) are mineral elements that have shown a reduction in the damage caused by tan spot (Pyrenophora tritici-repentis (Ptr)) in wheat. However, the effects of these elements were studied separately, and the N and Si interaction effect on wheat resistance to tan spot remains elusive. Histocytological and biochemical defense responses against Ptr in wheat leaves treated with Si (+Si) at low (LN) and high N (HN) inputs were investigated. Soil amendment with Si reduced the tan spot severity in 18% due to the increase in the leaf Si concentration (around 30%), but it was affected by the N level used. The superoxide dismutase (SOD) activity was higher in +Si plants and inoculated with Ptr, leading to early and higher H2O2 and callose accumulation in wheat leaf. Interestedly, phenylalanine ammonia-lyase (PAL) activity was induced by the Si supplying, being negatively affected by the HN rate. Meanwhile, catalase (CAT), and peroxidase (POX) activities showed differential response patterns according to the Si and N rates used. Tan spot severity was reduced by both elements, but their interaction does not evidence synergic effects in this disease's control. Wheat plants from -Si and HN and +Si and LN treatments recorded lower tan spot severity.

Effect of Chemical Treatments on the Mechanical Properties of Jute/Polyester Composites.

Natural fiber composites have been extensively studied for structural applications, with recent exploration into their potential for various uses. This study investigates the impact of chemical treatments on the properties of Brazilian jute woven fabric/polyester resin composites. Sodium hydroxide, hydrogen peroxide, and peracetic acid were utilized to treat the jute fabrics, followed by resin transfer molding (RTM) to form the composites. Evaluation included water absorption, flexural strength, tensile strength, and short-beam strength. The alkaline treatment induced changes in the chemical composition of the fibers' surface. Chemical treatments resulted in increased flexural and short-beam strength of the composites, with no significant alterations in tensile properties. The hydrogen peroxide treatment exhibited lower water absorption, suggesting its potential as a viable option for enhancing the performance of these composites.

Study on peripheral antinociception induced by hydrogen peroxide (H2O2): characterization and mechanisms.

The present study aimed to evaluate the possible peripheral H2O2-induced antinociception and determine the involvement of opioidergic, cannabinoidergic and nitrergic systems, besides potassium channels in its antinociceptive effect. Prostaglandin E2 was used to induce hyperalgesia in male Swiss mice using the mechanical paw pressure test. H2O2 (0.1, 0.2, 0.3 µg/paw) promoted a dose-dependent antinociceptive effect that was not observed in contralateral paw. Female mice also showed antinociception in the model. The partial H2O2-induced antinociception was potentiated by the inhibitor of catalase enzyme, aminotriazole (40, 60, 80 µg/paw). The antinociception was not reversed by opioid and cannabinoid receptor antagonists naloxone, AM 251 and AM 630. The involvement of nitric oxide (NO) was observed by the reversal of H2O2-induced antinociception using the non-selective inhibitor of nitric oxide synthases L-NOarg and by inhibition of iNOS (L-NIL), eNOS (L-NIO) and nNOS (L-NPA). ODQ, a cGMP-forming enzyme selective inhibitor, also reversed the antinociception. The blockers of potassium channels voltage-gated (TEA), ATP-sensitive (glibenclamide), large (paxillin) and small (dequalinium) conductance calcium-activated were able to revert H2O2 antinociception. Our data suggest that H2O2 induced a peripheral antinociception in mice and the NO pathway and potassium channels (voltage-gated, ATP-sensitive, calcium-activated) are involved in this mechanism. However, the role of the opioid and cannabinoid systems was not evidenced.

Bioinspired Tetranuclear Manganese Cubane Complex as an Efficient Molecular Electrocatalyst for Two-Electron Water Oxidation Towards Hydrogen Peroxide.

Stable homogeneous two-electron water oxidation electrocatalysts are highly demanded to understand the precise mechanism and reaction intermediates of electrochemical H2O2 production. Here we report a tetranuclear manganese complex with a cubane structure which can electrocatalyze water oxidation to hydrogen peroxide under alkaline and neutral conditions. Such a complex demonstrates an optimal Faradaic efficiency (FE) of 87 %, which is amongst (if not) the highest FE(H2O2) of reported homogeneous and heterogeneous electrocatalysts. In addition, active species were identified and co-catalysts were excluded through ESI-MS characterization. Furthermore, we identified water binding sites and isolated one-electron oxidation intermediate by chemical oxidation of the catalyst in the presence of water substrates. It is evident that efficient proton-accepting electrolytes avoid rapid proton building-up at electrode and substantially improve reaction rate and selectivity. Accordingly, we propose a two-electron catalytic cycle model for water oxidation to hydrogen peroxide with the bioinspired molecular electrocatalyst. The present work is expected to provide an ideal platform to elucidate the two-electron WOR mechanism at the atomic level.

Sildenafil Reverses the Neuropathological Alzheimer's Disease Phenotype in Cholinergic-Like Neurons Carrying the Presenilin 1 E280A Mutation.

Background: Familial Alzheimer's disease (FAD) presenilin 1 E280A (PSEN 1 E280A) is characterized by functional impairment and the death of cholinergic neurons as a consequence of amyloid-ß (Aß) accumulation and abnormal phosphorylation of the tau protein. Currently, there are no available therapies that can cure FAD. Therefore, new therapies are urgently needed for treating this disease. Objective: To assess the effect of sildenafil (SIL) on cholinergic-like neurons (ChLNs) harboring the PSEN 1 E280A mutation. Methods: Wild-type (WT) and PSEN 1 E280A ChLNs were cultured in the presence of SIL (25µM) for 24 h. Afterward, proteinopathy, cell signaling, and apoptosis markers were evaluated via flow cytometry and fluorescence microscopy. Results: We found that SIL was innocuous toward WT PSEN 1 ChLNs but reduced the accumulation of intracellular Aß fragments by 87%, decreased the non-physiological phosphorylation of the protein tau at residue Ser202/Thr205 by 35%, reduced the phosphorylation of the proapoptotic transcription factor c-JUN at residue Ser63/Ser73 by 63%, decreased oxidized DJ-1 at Cys106-SO3 by 32%, and downregulated transcription factor TP53 (tumor protein p53), BH-3-only protein PUMA (p53 upregulated modulator of apoptosis), and cleaved caspase 3 (CC3) expression by 20%, 32%, and 22%, respectively, compared with untreated mutant ChLNs. Interestingly, SIL also ameliorated the dysregulation of acetylcholine-induced calcium ion (Ca2+) influx in PSEN 1 E280A ChLNs. Conclusions: Although SIL showed no antioxidant capacity in the oxygen radical absorbance capacity and ferric ion reducing antioxidant power assays, it might function as an anti-amyloid and antiapoptotic agent and functional neuronal enhancer in PSEN 1 E280A ChLNs. Therefore, the SIL has therapeutic potential for treating FAD.

Comparative evaluation of hydrogen peroxide and chlorhexidine mouthwash on salivary interleukin-1ß levels in patients with type 2 diabetes mellitus and chronic periodontitis: a randomized controlled clinical trial / Evaluación comparativa de enjuague bucal con peróxido de hidrógeno y clorhexidina sobre los niveles de interleucina-1ß salival en pacientes con diabetes mellitus tipo 2 y periodontitis crónica: ensayo clínico controlado aleatorio

Introduction: Periodontal inflammation causes dysbiosis and change in the microbiota. Nonsurgical periodontal therapy (NSPT) helps in removal of plaque and restoring periodontal health. Various adjunctive therapy like use of mouthwash helps in maintenance of periodontal health and reducing inflammatory load. Materials and Methods: A total of 108 subjects diagnosed with type 2 diabetes mellitus and periodontitis were divided into three groups: Group 1 received NSPT and rinsing with 0.2% chlorhexidine mouthwash for 3 months, Group 2 received NSPT and rinsing with 1.5% hydrogen peroxide mouthwash for 3 months, Group 3- received NSPT only (control group). The clinical parameters measured included Plaque Index (PI), Gingival Index (GI), Bleeding on probing (BOP) and probing (PD) at baseline, 1, 2, 3 months follow up. Salivary interleukin 1ßlevels were measured at baseline and 3 months interval. Results: Group 1, 2 and 3 showed significant reduction in PI, GI, BOP and PD at 1 and 3 months follow up (p<0.05). However, Intergroup comparison of clinical parameters showed significant reduction in group 1 and 2 when compared with group 3 (p<0.05). Salivary interleukin 1-ß levels showed significant reduction from baseline to 3 months in all the three groups and intergroup comparison didn't show any significant changes, (p>0.05). Conclusions: Hydrogen peroxide mouthwash as an adjunct to NSPT can be considered as a safe and effective measure to reduce periodontal inflammation in type 2 diabetes mellitus patients with chronic periodontitis.

Introducción: La inflamación periodontal causa disbiosis y cambios en la microbiota. La terapia periodontal no quirúrgica (NSPT) ayuda a eliminar la placa y restaurar la salud periodontal. Diversas terapias complementarias, como el uso de enjuague bucal, ayudan a mantener la salud periodontal y reducir la carga inflamatoria. Materiales y Métodos: Un total de 108 sujetos diagnosticados con diabetes mellitus tipo 2 y periodontitis se dividieron en tres grupos: el grupo 1 recibió NSPT y enjuague con enjuague bucal de clorhexidina al 0,2% durante 3 meses, el grupo 2 recibió NSPT y enjuague con enjuague bucal de peróxido de hidrógeno al 1,5% durante 3 meses, y el Grupo 3 recibió NSPT únicamente (grupo de control). Los parámetros clínicos medidos fueron el índice de placa (PI), el índice gingival (GI), el sangrado al sondaje (BOP) y al sondaje (PD) al inicio del estudio, 1, 2, y 3 meses de seguimiento. Los niveles de interleucina 1ß en saliva se midieron al inicio y a los 3 meses. Resultado: Los grupos 1, 2 y 3 mostraron una reducción significativa en IP, GI, BOP y PD al mes y 3 meses de seguimiento (p<0,05). Sin embargo, la comparación intergrupal de los parámetros clínicos mostró una reducción significativa en los grupos 1 y 2 en comparación con grupo 3 (p<0,05). Los niveles de interleucina 1-ß salival mostraron una reducción significativa desde el inicio hasta los 3 meses en los tres grupos y la comparación entre grupos no mostró ningún cambio significativo (p>0,05). Conclusión: El enjuague bucal con peróxido de hidrógeno como complemento de la NSPT puede considerarse una medida segura y eficaz para reducir la inflamación periodontal en pacientes con diabetes mellitus tipo 2 y periodontitis crónica.

A Physiological Approach to Explore How Thioredoxin-Glutathione Reductase (TGR) and Peroxiredoxin (Prx) Eliminate H2O2 in Cysticerci of Taenia.

Peroxiredoxins (Prxs) and glutathione peroxidases (GPxs) are the main enzymes of the thiol-dependent antioxidant systems responsible for reducing the H2O2 produced via aerobic metabolism or parasitic organisms by the host organism. These antioxidant systems maintain a proper redox state in cells. The cysticerci of Taenia crassiceps tolerate millimolar concentrations of this oxidant. To understand the role played by Prxs in this cestode, two genes for Prxs, identified in the genome of Taenia solium (TsPrx1 and TsPrx3), were cloned. The sequence of the proteins suggests that both isoforms belong to the class of typical Prxs 2-Cys. In addition, TsPrx3 harbors a mitochondrial localization signal peptide and two motifs (-GGLG- and -YP-) associated with overoxidation. Our kinetic characterization assigns them as thioredoxin peroxidases (TPxs). While TsPrx1 and TsPrx3 exhibit the same catalytic efficiency, thioredoxin-glutathione reductase from T. crassiceps (TcTGR) was five and eight times higher. Additionally, the latter demonstrated a lower affinity (>30-fold) for H2O2 in comparison with TsPrx1 and TsPrx3. The TcTGR contains a Sec residue in its C-terminal, which confers additional peroxidase activity. The aforementioned aspect implies that TsPrx1 and TsPrx3 are catalytically active at low H2O2 concentrations, and the TcTGR acts at high H2O2 concentrations. These results may explain why the T. crassiceps cysticerci can tolerate high H2O2 concentrations.