Theoretical study of hydrogen peroxide interacting with DNA base and DNA base pair in terms of ab initio method and ABEEMσπ/MM fluctuating charge potential model

The optimized geometries, interaction energies, dipole moments, and vibrational frequencies of guanine-hydrogen peroxide (GHP), cytosine-hydrogen peroxide (CHP), adenine-hydrogen peroxide (AHP), thymine-hydrogen peroxide (THP), guanine–cytosine-hydrogen peroxide (GC-(HP)_n(n = 1–2)), and adenine–thymine-hydrogen peroxide (AT-(HP)_n(n = 1–2)) complexes are investigated by ab initio methods and ABEEMσπ/MM fluctuating charge potential model. All geometries of guanine–cytosine-hydrogen peroxide (G–C-HP) and adenine–thymine-hydrogen peroxide (A–T-HP) complexes were obtained using B3LYP/6-311++G(d,p) method, and the energies were determined at the MP2/6-311++G(2d,2p) level with BSSE corrections. The ABEEMσπ/MM model gives reasonable geometries and interaction energies compared with the present ab initio methods. For G–C-HP and A–T-HP clusters, the linear coefficient of the interaction energies all reaches 0.998, and the average absolute deviation (AAD) are 0.95 and 1.42 kcal/mol, respectively, when compared with MP2/6-311++G(2d,2p)‖B3LYP/6-311++G(d,p) method. Moreover, the variations of hydrogen bond length of guanine–cytosine and adenine–thymine base pair affected by hydrogen peroxide molecules computed by ABEEMσπ/MM model are all obtained reasonable accordance with B3LYP results. The current study will avail to understanding the physiological relevance in DNA damage.     

Evaluation of hydrogen peroxide-assisted endoscopic ultrasonography-guided necrosectomy in walled-off pancreatic necrosis: A single-center experience

Hydrogen peroxide is a liquid that functions in mechanical removal of the necrotic tissue via the elimination of tissue debris.In this study, we aimed to evaluate the effectiveness of the use of hydrogen peroxide in necrosectomy treatment of walled-off pancreatic necrosis.Records of 24 patients who were diagnosed with pancreatic necrosis or walled-off pancreatic necrosis and underwent endoscopic necrosectomy (EN) were retrospectively assessed. Patients were divided into 2 groups; hydrogen peroxide used for treatment or not used, and these 2 groups were compared.A total of 24 patients underwent endoscopic intervention for walled-off pancreatic necrosis. Procedural success was comparable between the 2 groups. During the post-procedural follow-up, the duration of the hospital stay, recurrence, and complication rates were found to be similar in both groups. The mean number of the endoscopic interventions was significantly lower in the hydrogen peroxide group (4.2 ± 1.4 vs 6.1 ± 4.2; P = .01).The use of hydrogen peroxide for EN in walled-off pancreatic necrosis patients seems to have similar efficiency and safety. However, it can be said that the use of hydrogen peroxide could reduce the number of endoscopic procedures.     

Adriamycin stimulates proliferation of human lymphoblastic leukaemic cells via a mechanism of hydrogen peroxide (H2O2) production

It is becoming clear that adriamycin cytotoxicity may be mediated by semiquinone-free radicals derived from the drug itself and reactive oxygen species (ROS). Recent evidence supports the concept that low concentrations of ROS are able to stimulate cell proliferation, and, based on the observation that subtoxic concentrations of adriamycin can also induce cell proliferation, we hypothesize that low concentrations of adriamycin stimulate cell proliferation by a ROS generation mechanism. We have employed spin-trapping and electron spin resonance (ESR) spectroscopy to investigate the nature of the adriamycin-generated ROS. The spin trap 3,5-dibromo-4-nitrosobenzenesulphonate (DBNBS), which is oxidized in the presence of H₂O₂ and peroxidase enzymes, was used to produce a characteristic three-line spectrum, and it was found that an identical spectrum was produced by human lymphoblastic leukaemic cells (CCRF-CEM cells) after exposure to adriamycin. We tested our hypothesis further by exposing CCRF-CEM cells to subtoxic concentrations of adriamycin (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and low concentrations of H₂O₂ (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and subsequently monitored cell proliferation. We found that low concentrations of both adriamycin and H₂O₂ significantly stimulate CCRF-CEM cell proliferation. We therefore conclude that subtoxic concentrations of adriamycin are likely to induce cell proliferation via an H₂O₂ mediated mechanism.     

Protective Effect of Total Phenolic Compounds from Inula helenium on Hydrogen Peroxide-induced Oxidative Stress in SH-SY5Y Cells

Inula helenium has been reported to contain a large amount of phenolic compounds, which have shown promise in scavenging free radicals and prevention of neurodegenerative diseases. This study is to investigate the neuroprotective effects of total phenolic compounds from I. helenium on hydrogen peroxide-induced oxidative damage in human SH-SY5Y cells. Antioxidant capacity of total phenolic compounds was determined by radical scavenging activity, the level of intracellular reactive oxygen species and superoxide dismutase activity. The cytotoxicity of total phenolic compounds was determined using a cell counting kit-8 assay. The effect of total phenolic compounds on cell apoptosis due to hydrogen peroxide-induced oxidative damage was detected by Hoechst 33258 and Annexin-V/PI staining using fluorescence microscope and flow cytometry, respectively. Mitochondrial function was evaluated using the mitochondrial membrane potential and mitochondrial ATP synthesis by JC-1 dye and high performance liquid chromatography, respectively. It was shown that hydrogen peroxide significantly induced the loss of cell viability, increment of apoptosis, formation of reactive oxygen species, reduction of superoxide dismutase activity, decrease in mitochondrial membrane potential and a decrease in adenosine triphosphate production. On the other hand, total phenolic compounds dose-dependently reversed these effects. This study suggests that total phenolic compounds exert neuroprotective effects against hydrogen peroxide-induced oxidative damage via blocking reactive oxygen species production and improving mitochondrial function. The potential of total phenolic compounds and its neuroprotective mechanisms in attenuating hydrogen peroxide-induced oxidative stress-related cytotoxicity is worth further exploration.     

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells

Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH₂Cl₂) were investigated against cytotoxic and genotoxic effects of H₂O₂ in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15–250?μg ml^?1), defatted fraction (15–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and toxic concentration of H₂O₂ (200?µM) at 37?°C for 2?h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25–250?μg ml^?1), defatted fraction (25–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and H₂O₂ (25?µM) at 4?°C for 20?min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC₅₀ values of TME, defatted fraction and CH₂Cl₂ fraction against DNA damage were determined as 48, 138 and 8?μg ml^?1, respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.     

血管过氧化物酶1介导的氧化应激在心血管疾病中的研究进展

血管过氧化物酶1(VPO1)是心血管系统新近发现的血红素过氧化物酶超家族成员,可催化NADPH氧化酶(NOX)来源的过氧化氢(H₂O₂)生成次氯酸(HClO),进而加重氧化应激,在高血压、动脉粥样硬化、心肌梗死和肺动脉高压等多种心血管疾病的发生发展过程中具有重要作用。本文主要就VPO1介导的氧化应激在心血管疾病中的作用及潜在机制进行综述。     

3％双氧水喷洒对老年急性上消化道出血病人胃腔视野改善情况

目的 评价3％双氧水对老年急性上消化道出血病人胃腔视野改善情况。方法 2000年3月-2003年12月对228例老年急性上消化道出血进行急诊胃镜检查,64例因胃腔视野不清末发现出血病灶,进入本研究,其中男38例,女26例。先对可疑出血病灶及胃腔照相,再通过活检孔向胃腔喷洒200 ml生理盐水,3分钟后吸尽胃腔液体,照相后换用200ml 3％双氧水喷洒,3分钟后吸尽胃腔液体,再对出血病灶及胃腔照相。由第三位胃镜专家对照片进行视野清晰度评分,同时观察出血部位,出血病灶性质、出血病灶止血情况。结果 喷洒3％双氧水后胃腔视野清晰度评分为2.26±0.23,发现出血部位88％(50／57)、确定出血病灶性质82.46％(47／57),活动性出血停止71.9％(41／57),而喷洒生理盐水后则分别为0.44±0.25、11％(7／64)、7.81％(5／64)、6.25％(4／64),二者相比均有非常显著性差异,P<0.001;42％患者有轻微上腹不适症状。结论 3％双氧水喷洒能改善老年人急性上消化道出血患者胃腔视野清晰状况,提高胃镜诊断率、并有较高的止血率,无明显不良反应,值得临床推广应用。     

依布硒啉对心肌缺血再灌注损伤大鼠心功能的保护作用及其机制

目的探讨依布硒啉(Ebs)对心肌缺血再灌注损伤大鼠心功能的保护作用及其机制。方法取24只雄性大鼠,结扎其冠状动脉左前降支30 min、灌注90 min制作心肌缺血再灌注损伤模型,观察Ebs对大鼠心功能、心肌酶学和脂质过氧化的影响。结果Ebs能够对抗心肌缺血再灌注引起的左心室内压(LVSP)、左心室内压最大上升与下降速率(±dp/dtmax)、动脉血压下降,并能够稳定心肌组织Na -K -ATPase和Ca2 -Mg2 -AT-Pase活性,降低丙二醛(MDA)含量和增高SOD活性。结论提示依布硒啉(Ebs)对大鼠心肌缺血再灌注引起的心功能减弱具有明显的保护作用,其机制可能为改善能量代谢障碍,抑制自由基生成或清除氧自由基。     

Effects of catalase and 1400W on the number of interleukin-4 and interferon-γ secreting spleen cells in mice injected with ovalbumin and alum

Context: Alum is thought to induce inflammation resulting in the release of danger signals such as uric acid (UA) which in turn enhances the immune response to an antigen. Hydrogen peroxide (H₂O₂) is produced as a byproduct in the purine catabolic pathway that leads to the production of UA. In addition, serum nitric oxide (NO) levels are increased in inflammation.

Objective: To further explore the mechanism of action of alum, this study was designed to determine the effects of catalase and 1400W on the number of interleukin-4 (IL-4) and interferon-γ (IFN-γ) secreting spleen cells in mice given ovalbumin (OVA) with alum.

Materials and methods: Groups of BALB/c mice were injected intraperitoneally with alum + OVA, alum, OVA, catalase, or 1400W. Other groups were treated with catalase or 1400W and given alum + OVA. The number of IL-4 and IFN-γ secreting spleen cells were determined at days 4 and 7 postinjection by enzyme-linked immunosorbent spot (ELISPOT).

Results: Catalase and 1400W caused a decrease in the number of IL-4 secreting spleen cells induced by alum + OVA. 1400W caused a decline in the IFN-γ secreting spleen cells induced by alum + OVA. Catalase caused an increase in IFN-γ secreting spleen cells.

Discussion and conclusion: It appears that H₂O₂ and NO are needed for alum-induced production of a T-helper 2 cytokine. NO also appears to be needed, whereas H₂O₂ appeared to inhibit an alum-induced production of a T-helper 1 cytokine. These results might explain why alum is mainly a promoter of a T-helper 2 response.