过氧化氢（H2O2）通过Fenton反应在体内和体外对DNA的毒性损伤

Toxic DNA damage by H2O2 through the Fenton reaction in vivo and in vitro

　

大肠杆菌暴露于低浓度的过氧化氢会导致DNA损伤，导致诱变并杀死细菌，而较高浓度的过氧化物会减少这种损害。早期的研究表明，直接DNA氧化剂是过氧化氢的衍生物，其形成依赖于细胞代谢。

这种氧化剂的产生取决于还原当量和铁物质（ferrous specifies)的可获得性，它们一起介导芬顿（Fenton)反应，其中亚铁将过氧化氢还原成反应性基团。

建立了体外Fenton系统，该系统产生DNA链断裂并使噬菌体失活，并且还通过高浓度的过氧化物再现了对DNA损伤的抑制。体内和体外系统中的直接DNA氧化剂表现出与游离羟自由基不同的反应性，并且可替代地是自由基。

　

Toxic DNA damage by H2O2 through the Fenton reaction in vivo and in vitro

 

Exposure of Escherichia coli to low concentrations of hydrogen peroxide results in DNA damage that causes mutagenesis and kills the bacteria, whereas higher concentrations of peroxide reduce the amount of such damage. Earlier studies indicated that the direct DNA oxidant is a derivative of hydrogen peroxide whose formation is dependent on cell metabolism.

The generation of this oxidant depends on the availability of both reducing equivalents and an iron species, which together mediate a Fenton reaction in which ferrous iron reduces hydrogen peroxide to a reactive radical.

An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide. The direct DNA oxidant both in vivo and in this in vitro system exhibits reactivity unlike that of a free hydroxyl radical and may instead be a ferryl radical.

Toxic DNA damage by H2O2 through the Fenton reaction in vivo and in vitro  https://www.researchgate.net/publication/20321067_Toxic_DNA_damage_by_H2O2_through_the_Fenton_reaction_in_vivo_and_in_vitro

　

http://www.itqb.unl.pt/~Metalloproteins_Bioenergetics/oxygen_tox.htm

　

过氧化氢使病毒失活

Virus inactivation by hydrogen peroxide

[俄文文章]

Mentel'R，Shirrmakher R，Kevich A，DreĭzinRS，Shmidt I.

抽象

在体外研究了过氧化氢（H2O2）对3型和6型腺病毒，腺相关病毒4型，鼻病毒1A，1B和7型，粘病毒，甲型和乙型流感，呼吸道合胞病毒，龙株和冠状病毒株229E的影响。 H2O2浓度和暴露时间。 3％浓度的H 2 O 2在1-30分钟内灭活所研究的所有病毒。发现冠状病毒和流感病毒最敏感。呼肠孤病毒，腺病毒和腺相关病毒相对稳定。 H2O2是病毒灭活的便利手段。

Vopr Virusol。 1977年11月至12月;（6）：731-3。

　

Virus inactivation by hydrogen peroxide

[Article in Russian]

Mentel' R, Shirrmakher R, Kevich A, Dreĭzin RS, Shmidt I.

Abstract

The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation.

Vopr Virusol. 1977 Nov-Dec;(6):731-3.

PMID: 203115

https://www.ncbi.nlm.nih.gov/pubmed/203115

　

　

过氧化氢灭活狂犬病病毒

Inactivation of rabies virus by hydrogen peroxide

　

强调

•我们在疫苗生产中引入3％过氧化氢（H2O2）溶液作为狂犬病病毒的潜在灭活剂。

 

•H2O2在2小时内导致病毒完全失活。

 

•H2O2灭活的病毒制剂被证明是安全的和免疫原性的。

 

•H2O2减少了灭活过程的时间和成本。

 

摘要

开发针对传染性病原体的安全和保护性疫苗仍然是一项挑战。狂犬病病毒的灭活是疫苗和其他研究试剂生产中的关键步骤。 β-丙内酯（βPL）;目前使用的狂犬病病毒灭活剂价格昂贵，并被证明对动物有致癌作用。本研究旨在研究过氧化氢（H2O2）在不影响其抗原性和免疫原性的情况下不可逆地灭活狂犬病毒的能力，以寻求安全，有效和廉价的替代灭活剂。 H2O2 3％在暴露2小时内快速灭活Vero细胞适应的固定狂犬病病毒株，命名为FRV / K，而不影响其抗原性或免疫原性。没有检测到残留的感染性病毒，并且与用经典灭活剂βPL灭活的相同病毒收获物相比，证明H2O2灭活的疫苗是安全有效的。用H2O2灭活的狂犬病病毒免疫的小鼠产生足够水平的抗体，并在用致死CVS病毒攻击时受到保护。这些发现强化了H2O2可以代替βPL作为狂犬病毒灭活剂的思想，以减少灭活过程的时间和成本。

Inactivation of rabies virus by hydrogen peroxide

　

Highlights

• We introduce 3% hydrogen peroxide (H2O2) solution as potential inactivating agent for rabies virus in production of vaccines.

 

• H2O2 caused complete inactivation of the virus within 2 h.

 

• H2O2-inactivated virus preparation proved to be safe and immunogenic.

 

• H2O2 reduced time and cost of inactivation process.

　

Abstract

Development of safe and protective vaccines against infectious pathogens remains a challenge. Inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. Beta-propiolactone (βPL); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. This study aimed to investigate the ability of hydrogen peroxide (H2O2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenicity in pursuit of finding safe, effective and inexpensive alternative inactivating agents. H2O2 3% rapidly inactivated a Vero cell adapted fixed rabies virus strain designated as FRV/K within 2 h of exposure without affecting its antigenicity or immunogenicity. No residual infectious virus was detected and the H2O2-inactivated vaccine proved to be safe and effective when compared with the same virus harvest inactivated with the classical inactivating agent βPL. Mice immunized with H2O2-inactivated rabies virus produced sufficient level of antibodies and were protected when challenged with lethal CVS virus. These findings reinforce the idea that H2O2 can replace βPL as inactivating agent for rabies virus to reduce time and cost of inactivation process.

Vaccine

Volume 34, Issue 6, 3 February 2016, Pages 798-802

Vaccine

Author links open overlay panelAsmaa A.Abd-ElghaffaraAmal E.AlibAbeer A.BoseilacMagdy A.Aminb

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https://doi.org/10.1016/j.vaccine.2015.12.041Get rights and content

　

Keywords

Rabies Hydrogen peroxide Inactivation Vaccine Immunity

Inactivation of rabies virus by hydrogen peroxide - ScienceDirect  https://www.sciencedirect.com/science/article/pii/S0264410X15018381

　

Inactivation of Hepatitis a Virus and MS2 by Ozone and Ozone-Hydrogen Peroxide in Buffered Water

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The comparative inactivation of highly purified hepatitis A virus (HAV) and MS2 by 1 mg H2O2/L, 2.0 and 0.4 mg O3/L, and 2.0 mg O3/L plus 0.6, 1.0, or 1.6 mg H2O2/L, at 3-10°C, in 0.01 M phosphate buffer (pH 6-10) was determined. Both HAV and MS2 were completely inactivated (3.9-6 log10) within 5 seconds in ozone solutions. Hydrogen peroxide did not inactivate MS2, but did inactivate 95% of the HAV. Both HAV and MS2 were completely (3.3-5.5 log) inactivated within 5 seconds in the oxidant mixtures at pH 6-8, but MS2 survival exceeded that of HAV at pH 10. MS2 was found to be a good model for predicting HAV inactivation by ozone and mixtures of ozone and hydrogen peroxide when both viruses are purified in the same manner.

keywords:Disinfection, ozone, hydrogen peroxide, hepatitis A virus, MS2

Source:

Richard M. Hall  Mark D. Sobsey

Water Sci Technol (1993) 27 (3-4): 371-378.

https://doi.org/10.2166/wst.1993.0377

Inactivation of Hepatitis a Virus and MS2 by Ozone and Ozone-Hydrogen Peroxide in Buffered Water | Water Science and Technology | IWA Publishing  https://iwaponline.com/wst/article/27/3-4/371/4810/Inactivation-of-Hepatitis-a-Virus-and-MS2-by-Ozone

　

The Fenton Reaction. Dependence of the Rate on pH

 

Mordechai L. Kremer

Department of Physical Chemistry, Hebrew University, Jerusalem 91904, Israel

J. Phys. Chem. A, 2003, 107 (11), pp 1734–1741

DOI: 10.1021/jp020654p

Publication Date (Web): February 20, 2003

Copyright © 2003 American Chemical Society

Cite this:J. Phys. Chem. A 2003,  107, 11, 1734-1741

 

Abstract

The pH dependence of the evolution of O2 in the Fenton reaction has been studied by using an indirect method for measuring [O2]. The results confirmed observations of previous workers, namely, that the evolution of O2 diminished as the pH was lowered. A quantitative analysis of the dependence of [O2] and [Fe2+] during the reaction as a function of time showed that the pH dependence of the course of the reaction can be accounted for by assuming an acid base reaction of the active intermediate:  FeO2+ + H+ ⇌ FeOH3+. FeOH3+ is the active entity in the reaction with Fe2+ to produce Fe3+ ions, while the other form FeO2+ is involved in reactions leading to O2 evolution.

https://pubs.acs.org/doi/abs/10.1021/jp020654p

　

　

Interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials: A review.

J Environ Sci (China). 2016 Jan;39:97-109. doi: 10.1016/j.jes.2015.12.003. Epub 2015 Dec 28.

He J1, Yang X2, Men B3, Wang D4.

Author information

Abstract

The heterogeneous Fenton reaction can generate highly reactive hydroxyl radicals (OH) from reactions between recyclable solid catalysts and H2O2 at acidic or even circumneutral pH. Hence, it can effectively oxidize refractory organics in water or soils and has become a promising environmentally friendly treatment technology. Due to the complex reaction system, the mechanism behind heterogeneous Fenton reactions remains unresolved but fascinating, and is crucial for understanding Fenton chemistry and the development and application of efficient heterogeneous Fenton technologies. Iron-based materials usually possess high catalytic activity, low cost, negligible toxicity and easy recovery, and are a superior type of heterogeneous Fenton catalysts. Therefore, this article reviews the fundamental but important interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials. OH, hydroperoxyl radicals/superoxide anions (HO2/O2(-)) and high-valent iron are the three main types of reactive oxygen species (ROS), with different oxidation reactivity and selectivity. Based on the mechanisms of ROS generation, the interfacial mechanisms of heterogeneous Fenton systems can be classified as the homogeneous Fenton mechanism induced by surface-leached iron, the heterogeneous catalysis mechanism, and the heterogeneous reaction-induced homogeneous mechanism. Different heterogeneous Fenton systems catalyzed by characteristic iron-based materials are comprehensively reviewed. Finally, related future research directions are also suggested.

 

KEYWORDS:

Heterogeneous Fenton reactions; ROS; interfacial mechanisms; iron-based materials

PMID: 26899649 DOI: 10.1016/j.jes.2015.12.003

Interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials: A review. - PubMed - NCBI  https://www.ncbi.nlm.nih.gov/pubmed/26899649

　

J Hazard Mater. 2014 Jun 30;275:121-35. doi: 10.1016/j.jhazmat.2014.04.054. Epub 2014 May 2.

Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation processes.

Bokare AD1, Choi W2.

Author information

Abstract

Iron-catalyzed hydrogen peroxide decomposition for in situ generation of hydroxyl radicals (HO(•)) has been extensively developed as advanced oxidation processes (AOPs) for environmental applications. A variety of catalytic iron species constituting metal salts (in Fe(2+) or Fe(3+) form), metal oxides (e.g., Fe2O3, Fe3O4), and zero-valent metal (Fe(0)) have been exploited for chemical (classical Fenton), photochemical (photo-Fenton) and electrochemical (electro-Fenton) degradation pathways. However, the requirement of strict acidic conditions to prevent iron precipitation still remains the bottleneck for iron-based AOPs. In this article, we present a thorough review of alternative non-iron Fenton catalysts and their reactivity towards hydrogen peroxide activation. Elements with multiple redox states (like chromium, cerium, copper, cobalt, manganese and ruthenium) all directly decompose H2O2 into HO(•) through conventional Fenton-like pathways. The in situ formation of H2O2 and decomposition into HO(•) can be also achieved using electron transfer mechanism in zero-valent aluminum/O2 system. Although these Fenton systems (except aluminum) work efficiently even at neutral pH, the H2O2 activation mechanism is very specific to the nature of the catalyst and critically depends on its composition. This review describes in detail the complex mechanisms and emphasizes on practical limitations influencing their environmental applications.

 

KEYWORDS:

Advanced oxidation processes (AOPs); Fenton; Hydrogen peroxide; Hydroxyl radical; Water treatment

PMID: 24857896 DOI: 10.1016/j.jhazmat.2014.04.054

Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation processes. - PubMed - NCBI  https://www.ncbi.nlm.nih.gov/pubmed/24857896

　

REFERENCES:

Pretreatment of whole blood using hydrogen peroxide and UV irradiation. Design of the advanced oxidation process  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568745/

　

Chemical Attributes of Iron that make it a Useful Serum-Free Medium Supplement:

 

The design of a stable and useful medium requires an understanding of the chemistry of iron. The management of this metal is a critical success factor in cell culture.

Iron exists in both the ferrous, and ferric state in physiological solutions. It is frequently added to cell culture media as a nitrate or sulfate salt. In solution, it undergoes redox cycling depending upon the medium’s composition of oxidizing and reducing agents, and its exposure to these agents. The susceptibility of iron to the medium’s redox potential depends upon the molecules that complex it. Iron complexes can form with bio-molecules such as amino acids, nucleotides, physiological chelators, and proteins. The specific complexes are very important because they determine whether the iron is available to participate in cell growth, to catalyze toxic reactions or becomes non-available to the system. Free or ineffectively sequestered iron can be very toxic to cells. Properly complexed iron is available to support cell life and is essential to the cell culture system.

The most appropriate extracellular physiological complexes of iron are with ferritin and transferrin. Ferritin is the primary storage molecule for iron.

Ferric Iron:

 

Ferric iron is the stable oxidative state of iron in aerobic conditions, and the normal oxidative state used by cells. In a solution at physiologic pH, ferric iron that is not bound by a chelator or carrier molecule will form ferric hydroxide complexes that are virtually insoluble. The chemistry is quite complex. However, it is not necessary to fully understand it to appreciate that iron may be lost due to the formation of these complexes. Ferric iron can be reduced to ferrous iron by strong reducing agents in the medium. Iron reducing agents of concern in cell culture include the superoxide radical and ascorbate. A widely studied cellular reductant and frequently used media component is ascorbate (Vitamin C). Ascorbate can reduce ferric:EDTA to ferrous:EDTA. Ferrrous:EDTA can catalyze the formation of hydroxyl free radicals through Fenton chemistry.

Both the loss of ferric iron due to precipitation and its reduction to ferrous iron are undesirable events in the extracellular milieu. Both of these occurrences are avoided when transferrin is included in the culture system. In view of the above facts, one should strongly consider whether adding iron salts directly to a medium is appropriate. This question becomes increasingly more important in serum-free medium where the protective qualities of serum are absent.

Ferrous Iron:

 

Ferric iron can be reduced to ferrous iron in cell culture media. Iron in the ferrous oxidative state that is free to participate in Fenton chemistry is a major source of oxidative stress in media. The reaction involves the ferrous iron catalyzed conversion of hydrogen peroxide into a hydroxide ion and a hydroxyl free radical with the concurrent oxidation of ferrous iron to ferric iron. This reaction is profoundly important in cell culture, because when it occurs, it creates the most damaging agent found in the cell culture system-the hydroxyl free radical. This radical will react with virtually any molecule in the medium or the cell. It is so reactive that it typically reacts very close to its site of formation. A major action of hydroxyl free radicals in cell culture involves the initiation of lipid peroxidation. Ferrous iron mediated lipid peroxidation can occur with iron in a number of chelated complexes: the ferrous iron can be chelated to phosphate, ADP, ATP, oxalate, and citrate.

Enzymes that catalyze the conversion of ferrous iron to ferric iron are ferroxidases. Ceruloplasmin, a serum protein, has a ferroxidase activity that accelerates the oxidation of ferritin bound ferrous iron into ferric iron and promotes its binding by transferrin. In the absence of ferroxidase activities, the conversion of ferrous iron to ferric iron is slow.

Ferrous and ferric iron will complex with thiols such as cysteine. The ferrous:cysteine complex can participate in the generation of hydroxyl free radicals through Fenton chemistry.

Ferric and Ferrous Iron in Cell Culture | China-Mainland | Sigma-Aldrich  https://www.sigmaaldrich.com/china-mainland/zh/life-science/cell-culture/learning-center/media-expert/iron.html

　

　

Reactive oxygen species at phospholipid bilayers: Distribution, mobility and permeation

Author links open overlay panelRodrigo M.Cordeiro

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https://doi.org/10.1016/j.bbamem.2013.09.016Get rights and content

Under an Elsevier user licenseopen archive

Highlights

•

Hydrophobic species such as O2 (and probably 1O2) accumulate in the membrane interior.

 

•

HO and HO2 penetrate in the membrane down to the region of the carbonylester groups.

 

•

HO2 adsorbs at the headgroups and becomes one order of magnitude more concentrated.

 

•

Due to membrane disorder, HO and HO2 can reach peroxidation sites at the lipid chains.

 

•

Accessibility of membrane antioxidants to ROS depends on differences in hydrophobicity.

 

 

Abstract

Reactive oxygen species (ROS) are involved in biochemical processes such as redox signaling, aging, carcinogenesis and neurodegeneration. Although biomembranes are targets for reactive oxygen species attack, little is known about the role of their specific interactions. Here, molecular dynamics simulations were employed to determine the distribution, mobility and residence times of various reactive oxygen species at the membrane–water interface. Simulations showed that molecular oxygen (O2) accumulated at the membrane interior. The applicability of this result to singlet oxygen (1O2) was discussed. Conversely, superoxide (O2−) radicals and hydrogen peroxide (H2O2) remained at the aqueous phase. Both hydroxyl (HO) and hydroperoxyl (HO2) radicals were able to penetrate deep into the lipid headgroups region. Due to membrane fluidity and disorder, these radicals had access to potential peroxidation sites along the lipid hydrocarbon chains, without having to overcome the permeation free energy barrier. Strikingly, HO2 radicals were an order of magnitude more concentrated in the headgroups region than in water, implying a large shift in the acid–base equilibrium between HO2 and O2−. In comparison with O2, both HO and HO2 radicals had lower lateral mobility at the membrane. Simulations revealed that there were intermittent interruptions in the H-bond network around the HO radicals at the headgroups region. This effect is expected to be unfavorable for the H-transfer mechanism involved in HO diffusion. The implications for lipid peroxidation and for the effectiveness of membrane antioxidants were evaluated.

 

Graphical abstract

Reactive oxygen species at phospholipid bilayers: Distribution, mobility and permeation - ScienceDirect  https://www.sciencedirect.com/science/article/pii/S0005273613003313