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.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

在非水介质中用表面引发接枝聚合法制备接枝微粒PHEMA-SiO2及其对槲皮素的氢键吸附性能

首先,将偶联剂γ-巯丙基三甲氧基硅烷(MPMS)上的巯基(-SH)键合在微米级硅胶(SiO₂)微粒表面,得到了改性微粒MPMS-SiO₂。在非水溶剂N,N-二甲基甲酰胺(DMF)中,使溶液中的过氧化苯甲酰(BPO)与改性微粒MPMS-SiO₂表面的巯基构成表面引发体系(-SH/BPO),于非水介质中在硅胶微粒表面实现了甲基丙烯酸羟乙酯(HEMA)的接枝聚合,成功制备出接枝微粒PHEMA-SiO₂,接枝度高达28 g/100 g。采用红外光谱(FT-IR)、热重分析(TG)及扫描电子显微镜(SEM)等手段对PHEMA-SiO₂进行了表征,研究了主要因素对HEMA表面引发接枝聚合的影响规律。在此基础上探索研究了PHEMA-SiO₂对槲皮素(Quercetin)的氢键吸附作用。研究结果表明:-SH/BPO引发体系可以顺利地引发HEMA在非水介质中的接枝聚合,适宜的温度为65℃,适宜的BPO用量为单体质量的1.0%。PHEMA-SiO₂与槲皮素分子之间会产生多位点普通氢键与π型氢键两种氢键相互作用,使PHEMA-SiO₂对槲皮素具有强吸附能力。溶剂分子对槲皮素的竞争吸附以及温度的升高均可使槲皮素在极性溶剂或质子性溶剂中吸附容量下降。     

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。     

气体信使硫化氢在大鼠肾血管性高血压中的调节作用

目的探讨硫化氢体系在肾血管性高血压形成及发展中的变化和作用。方法成年的雄性Wistar大鼠28只,随机分为对照组7只、双肾一夹组(two-kidney,one-clip,2KIC组)7只、2KIC+硫氢化钠(硫氢化钠为外源性硫化氢供者)组8只、假手术组6只,其中2KIC+硫氢化钠组每天腹腔注射硫氢化钠(56μmol/kg),对照组、2KIC组及假手术组注射相同剂量的生理盐水。相同条件饲养4周,4周后处死,检测血浆硫化氢水平,双肾硫化氢合酶的活性,血管紧张素Ⅱ,左心与全心重量比,光学显微镜下观察肾的显微结构变化。结果术后4周,2KIC组尾动脉压显著高于假手术组及2KIC+硫氢化钠组;2KIC组的血管紧张素Ⅱ显著高于假手术组和对照组;左心室与全心重量比值2KIC组高于对照组和假手术组;肾内硫化氢合酶的活性及血浆中硫化氢的含量2KIC组显著低于假手术组及对照组,2KIC+硫氢化钠组高于2KIC组。结论肾血管性高血压大鼠硫化氢体系受到严重抑制,可能是肾性高血压形成的重要因素,外源性的给予硫化氢供者有助于缓解高血压的形成。     

Managing Ulcerative Colitis by Increasing Hydrogen Production Via Oral Administration of Acarbose

The objective of the study was to investigate ulcerative colitis management through oral administration of acarbose. Acarbose has gained importance as a drug used widely to treat Diabetes Mellitus Type 2,as it acts on the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing postprandial glucose excursion. The main side-effect of treatment with Acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amounts of hydrogen. We found that the enteric benefits of Acarbose are partly due to be their ability to neutralise oxidative stress via increased production of H₂ in the gastrointestinal tract. Therefore, some symptoms of ulcerative colitis in human beings can be ameliorated by Acarbose.     

Bioinspired Photo‐Core‐Crosslinked and Noncovalently Connected Micelles From Functionalized Polystyrene and Poly(ethylene oxide) Homopolymers

In this paper, we report a simple and effective method for the preparation of stable core‐crosslinked micelles after the self‐assembly of thymine‐functionalized polystyrene (PVBT) and adenine‐terminated poly(ethylene oxide) (PEO‐A) homopolymers, and subsequent bioinspired photo‐crosslinking of the thymine units in PVBT. We obtained “graft‐like” copolymers from the interactions of PEO‐A with the PVBT chains through complementary multiple hydrogen bonding in a common solvent (dimethylformamide) after the addition of selective solvents (H₂O and MeCN for PVBT and PEO‐A, respectively). Stable micelles featuring PVBT as the core and PEO‐A as the shell were formed via selective solvent pairs; they were clearly visualized using transmission electronic microscopy and staining techniques. The shapes and sizes of the core/shell micelle structures did not change after exposure to UV light, revealing the enhanced dimensional stability of these photo‐core‐crosslinked micelles.