Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Evaluation of Decontamination Efficacy of Electrolytically Generated Hypochlorous Acid for the Vesicating Agent: A Multimodel Study

Author(s): Ajay Kumar Sharma, Sandeep Kumar Shukla*, Aman Kalonia, Priyanka Shaw, Kushagra Khanna, M. H. Yashavarddhan, Richa Gupta and Aseem Bhatnagar

Volume 23, Issue 2, 2022

Published on: 11 March, 2021

Page: [287 - 299] Pages: 13

DOI: 10.2174/1389201022666210311140922

Price: $65

Abstract

Background: Sulfur Mustard is a strong vesicant and chemical warfare agent that imposes toxicity to the lungs, eyes, and skin after accidental or intended exposure.

Objectives: The current study was intended to explore in vitro and in vivo decontamination properties of electrolytically generated HOCl (hypochlorous acid) against CEES (2-chloroethyle ethyle sulphide), a known sulfur mustard simulant & vesicating agent.

Methods: in vitro studies were carried out using UV spectroscopy and GC-MS methods. In vivo studies were performed in Strain A and immune-compromised mice by subcutaneous as well as prophylactic topical administration of HOCl pretreated CEES. The blister formation and mortality were considered as end-point. Histopathological study was conducted on skin samples by H & E method. DNA damage studies measuring γ-H2AX and ATM have been carried out in human blood using flow cytometry. Anti-bacterial action was tested by employing broth micro dilution methods. A comparative study was also carried out with known oxidizing agents.

Results: The topical application of pre-treated CEES at 5, 30 min and 1 h time points showed significant (p<0.001) inhibition of blister formation. DNA damage study showed reduced mean fluorescence intensity of DSBs nearly 17-20 times, suggesting that HOCl plays a protective role against DNA damage. Histopathology showed no sign of necrosis in the epidermis upto 5 min although moderate changes were observed at 30 min. Pretreated samples were analyzed for detection of reaction products with m/z value of 75.04, 69.08, 83.93, 85.95, 123.99, 126.00, and 108.97. HOCl showed a strong bactericidal effect at 40 ppm. The absorbance spectra of HOCl treated CEES showed lowered peaks in comparison to CEES alone and other oxidizing agents.

Conclusion: In a nutshell, our results signify the decontamination role of HOCl for biological surface application.

Keywords: CW agents, CEES, blister, HOCl, decontamination, DNA damage, necrosis.

« Previous Next »
Graphical Abstract

[1]
Abel, E.L.; Bubel, J.D.; Simper, M.S.; Powell, L.; McClellan, S.A.; Andreeff, M.; MacLeod, M.C.; DiGiovanni, J. Protection against 2-chloroethyl ethyl sulfide (CEES)-induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway. Toxicol. Appl. Pharmacol., 2011, 255(2), 176-183.
[http://dx.doi.org/10.1016/j.taap.2011.06.012] [PMID: 21723306]
[2]
Laskin, J.D.; Black, A.T.; Jan, Y.H.; Sinko, P.J.; Heindel, N.D.; Sunil, V.; Heck, D.E.; Laskin, D.L. Oxidants and antioxidants in sulfur mustard-induced injury. Ann. N. Y. Acad. Sci., 2010, 1203, 92-100.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05605.x] [PMID: 20716289]
[3]
Jowsey, P.A.; Williams, F.M.; Blain, P.G. DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide. Toxicology, 2009, 257(3), 105-112.
[http://dx.doi.org/10.1016/j.tox.2008.12.001] [PMID: 19111594]
[4]
Tewari-Singh, N.; Rana, S.; Gu, M.; Pal, A.; Orlicky, D.J.; White, C.W.; Agarwal, R. Inflammatory biomarkers of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced skin injury in SKH-1 hairless mice. Toxicol. Sci., 2009, 108(1), 194-206.
[http://dx.doi.org/10.1093/toxsci/kfn261] [PMID: 19075041]
[5]
Singh, B.; Prasad, G.K.; Pandey, K.S.; Danikhel, R.K.; Vijayaraghavan, R. Decontamination of Chemical Warfare Agents (Review Article). Def Sci., 2010, 60(4), 428-441.
[6]
Tewari-Singh, N.; Gu, M.; Agarwal, C.; White, C.W.; Agarwal, R. Biological and molecular mechanisms of sulfur mustard analogue-induced toxicity in JB6 and HaCaT cells: possible role of ataxia telangiectasia-mutated/ataxia telangiectasia-Rad3-related cell cycle checkpoint pathway. Chem. Res. Toxicol., 2010, 23(6), 1034-1044.
[http://dx.doi.org/10.1021/tx100038b] [PMID: 20469912]
[7]
Clingen, P.H.; Wu, J.Y.; Miller, J.; Mistry, N.; Chin, F.; Wynne, P.; Prise, K.M.; Hartley, J.A. Histone H2AX phosphorylation as a molecular pharmacological marker for DNA interstrand crosslink cancer chemotherapy. Biochem. Pharmacol., 2008, 76(1), 19-27.
[http://dx.doi.org/10.1016/j.bcp.2008.03.025] [PMID: 18508035]
[8]
Inturi, S.; Tewari-Singh, N.; Gu, M.; Shrotriya, S.; Gomez, J.; Agarwal, C.; White, C.W.; Agarwal, R. Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts. Free Radic. Biol. Med., 2011, 51(12), 2272-2280.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.08.020] [PMID: 21920433]
[9]
Jan, Y.H.; Heck, D.E.; Laskin, D.L.; Laskin, J.D. DNA damage signaling in the cellular responses to mustard vesicants. Toxicol. Lett., 2020, 326, 78-82.
[http://dx.doi.org/10.1016/j.toxlet.2020.03.008] [PMID: 32173488]
[10]
Talmage, S.; Watson, A.; Hauschild, V.; Munro, N.; King, J. Chemical warfare agent degradation and decontamination. Curr. Org. Chem., 2007, 11(3), 285-298.
[http://dx.doi.org/10.2174/138527207779940892]
[11]
Hakim, H.; Thammakarn, C.; Suguro, A.; Ishida, Y.; Kawamura, A.; Tamura, M.; Satoh, K.; Tsujimura, M.; Hasegawa, T.; Takehara, K. Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments. J. Vet. Med. Sci., 2015, 77(2), 211-215.
[http://dx.doi.org/10.1292/jvms.14-0413] [PMID: 25421399]
[12]
Peskin, A.V.; Winterbourn, C.C. Kinetics of the reactions of hypochlorous acid and amino acid chloramines with thiols, methionine, and ascorbate. Free Radic. Biol. Med., 2001, 30(5), 572-579.
[http://dx.doi.org/10.1016/S0891-5849(00)00506-2] [PMID: 11182528]
[13]
Carr, A.C.; van den Berg, J.J.; Winterbourn, C.C. Chlorination of cholesterol in cell membranes by hypochlorous acid. Arch. Biochem. Biophys., 1996, 332(1), 63-69.
[http://dx.doi.org/10.1006/abbi.1996.0317] [PMID: 8806710]
[14]
Prütz, W.A. Hypochlorous acid interactions with thiols, nucleotides, DNA, and other biological substrates. Arch. Biochem. Biophys., 1996, 332(1), 110-120.
[http://dx.doi.org/10.1006/abbi.1996.0322] [PMID: 8806715]
[15]
Martinez, J.E. The rotation of disinfectants principle: true or false. Pharm. Technol., 2009, 33(2), 58-71.
[16]
US Department of Agriculture – USDA. Technical evaluation Report; Agricultural Marketing Service, Agricultural Analytics Division for the USDA National Organic Program, 2015.
[17]
Kilkenny, C.; Browne, W.J.; Cuthill, I.C.; Emerson, M.; Altman, D.G. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage, 2012, 20(4), 256-260.
[http://dx.doi.org/10.1016/j.joca.2012.02.010] [PMID: 22424462]
[18]
Dong, J.; Hu, J.; Chi, Y.; Lin, Z.; Zou, B.; Yang, S.; Hill, C.L.; Hu, C. A polyoxoniobate-polyoxovanadate double-anion catalyst for simultaneous oxidative and hydrolytic decontamination of chemical warfare agent simulants. Angew. Chem. Int. Ed. Engl., 2017, 56(16), 4473-4477.
[http://dx.doi.org/10.1002/anie.201700159] [PMID: 28322483]
[19]
van der Fits, L.; Mourits, S.; Voerman, J.S.; Kant, M.; Boon, L.; Laman, J.D.; Cornelissen, F.; Mus, A.M.; Florencia, E.; Prens, E.P.; Lubberts, E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol., 2009, 182(9), 5836-5845.
[http://dx.doi.org/10.4049/jimmunol.0802999] [PMID: 19380832]
[20]
Meier, H.L.; Millard, C.B. Alterations in human lymphocyte DNA caused by sulfur mustard can be mitigated by selective inhibitors of poly(ADP-ribose) polymerase. Biochim. Biophys. Acta, 1998, 1404(3), 367-376.
[http://dx.doi.org/10.1016/S0167-4889(98)00078-0] [PMID: 9739165]
[21]
Cheng, A.; Zhao, T.; Tse, K.H.; Chow, H.M.; Cui, Y.; Jiang, L.; Du, S.; Loy, M.M.T.; Herrup, K. ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations. Proc. Natl. Acad. Sci. USA, 2018, 115(2), E292-E301.
[http://dx.doi.org/10.1073/pnas.1716892115] [PMID: 29279380]
[22]
Yashavarddhan, M.H.; Shukla, S.K.; Chaudhary, P.; Srivastava, N.N.; Joshi, J.; Suar, M.; Gupta, M.L. Targeting DNA repair through podophyllotoxin and rutin formulation in hematopoietic radioprotection: an in silico, in vitro, and in vivo study. Front. Pharmacol., 2017, 8, 750.
[http://dx.doi.org/10.3389/fphar.2017.00750] [PMID: 29163150]
[23]
Wiegand, I.; Hilpert, K.; Hancock, R.E. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc., 2008, 3(2), 163-175.
[http://dx.doi.org/10.1038/nprot.2007.521] [PMID: 18274517]
[24]
Elshikh, M.; Ahmed, S.; Funston, S.; Dunlop, P.; McGaw, M.; Marchant, R.; Banat, I.M. Resazurin-based 96-well plate microdilution method for the determination of minimum inhibitory concentration of biosurfactants. Biotechnol. Lett., 2016, 38(6), 1015-1019.
[http://dx.doi.org/10.1007/s10529-016-2079-2] [PMID: 26969604]
[25]
Brebu, M.; Ucar, S.; Vasile, C.; Yanik, J. Co-pyrolysis of pine cone with synthetic polymers. Fuel, 2010, 89, 1911-1918.
[http://dx.doi.org/10.1016/j.fuel.2010.01.029]
[26]
Lu, Q.; Tang, Z.; Zhang, Y.; Zhu, X.F. Catalytic upgrading of biomass fast pyrolysis vapors with Pd/SBA-15 catalysts. Ind. Eng. Chem. Res., 2010, 49, 2573-2580.
[http://dx.doi.org/10.1021/ie901198s]
[27]
ICH Topic Q 1 A (R2). Stability Testing of New Drug Substances and Products. European Medicines Agency. CPMP/ICH/2736/99.,. 2010.
[28]
Prokopowicz, Z.; Marcinkiewicz, J.; Katz, D.R.; Chain, B.M. Neutrophil myeloperoxidase: soldier and statesman. Arch. Immunol. Ther. Exp. (Warsz.), 2012, 60(1), 43-54.
[http://dx.doi.org/10.1007/s00005-011-0156-8] [PMID: 22143159]
[29]
Block, M.S.; Rowan, B.G. Hypochlorous Acid: A Review. J. Oral Maxillofac. Surg., 2020, 78(9), 1461-1466.
[http://dx.doi.org/10.1016/j.joms.2020.06.029] [PMID: 32653307]
[30]
Pegrift, R.Y.; Friedman, A.J. Topical hypochlorous acid (HOCl) as a potential treatment of pruritus. Curr. Dermatol. Rep., 2013, 2, 181-190.
[http://dx.doi.org/10.1007/s13671-013-0052-z]
[31]
Wang, L.; Bassiri, M.; Najafi, R.; Najafi, K.; Yang, J.; Khosrovi, B.; Hwong, W.; Barati, E.; Belisle, B.; Celeri, C.; Robson, M.C. Hypochlorous acid as a potential wound care agent: part I. Stabilized hypochlorous acid: a component of the inorganic armamentarium of innate immunity. J. Burns Wounds, 2007, 6e5
[PMID: 17492050]
[32]
Liu, L.; Ping, E.; Sun, J.; Zhang, L.; Zhou, Y.; Zhong, Y.; Zhou, Y.; Wang, Y. Multifunctional Ag@MOF-5@chitosan non-woven cloth composites for sulfur mustard decontamination and hemostasis. Dalton Trans., 2019, 48(20), 6951-6959.
[http://dx.doi.org/10.1039/C9DT00503J] [PMID: 31041972]
[33]
Vijayaraghavan, R.; Gautam, A.; Sharma, M. ]Medical countermeasures and other therapeutic strategies for sulfur mustard toxicity, Editor(s): Ramesh C. Gupta.Handbook of Toxicology of Chemical Warfare Agents; Academic Press, 2009, pp. 897-918..
[34]
Medical Management of Chemical Casualties. United States Army Medical Research Institute of Chemical Defense.. 1995.https://fas.org/nuke/guide/usa/doctrine/army/mmcch/Decontam.htm
[35]
Watt, B.E.; Proudfoot, A.T.; Vale, J.A. Hydrogen peroxide poisoning. Toxicol. Rev., 2004, 23(1), 51-57.
[http://dx.doi.org/10.2165/00139709-200423010-00006] [PMID: 15298493]
[36]
Mouret, S.; Wartelle, J.; Batal, M.; Emorine, S.; Bertoni, M.; Poyot, T.; Cléry-Barraud, C.; Bakdouri, N.E.; Peinnequin, A.; Douki, T.; Boudry, I. Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice. Toxicol. Lett., 2015, 232(1), 68-78.
[http://dx.doi.org/10.1016/j.toxlet.2014.09.022] [PMID: 25275893]
[37]
Dorandeu, F.; Taysse, L.; Boudry, I.; Foquin, A.; Hérodin, F.; Mathieu, J.; Daulon, S.; Cruz, C.; Lallement, G. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection. Hum. Exp. Toxicol., 2011, 30(6), 470-490.
[http://dx.doi.org/10.1177/0960327110373615] [PMID: 20547654]
[38]
Greenberg, S.; Kamath, P.; Petrali, J.; Hamilton, T.; Garfield, J.; Garlick, J.A. Characterization of the initial response of engineered human skin to sulfur mustard. Toxicol. Sci., 2006, 90(2), 549-557.
[http://dx.doi.org/10.1093/toxsci/kfi306] [PMID: 16141436]
[39]
Joseph, L.B.; Gerecke, D.R.; Heck, D.E.; Black, A.T.; Sinko, P.J.; Cervelli, J.A.; Casillas, R.P.; Babin, M.C.; Laskin, D.L.; Laskin, J.D. Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage. Exp. Mol. Pathol., 2011, 91(2), 515-527.
[http://dx.doi.org/10.1016/j.yexmp.2011.05.010] [PMID: 21672537]
[40]
Jain, A.K.; Tewari-Singh, N.; Orlicky, D.J.; White, C.W.; Agarwal, R. 2-Chloroethyl ethyl sulfide causes microvesication and inflammation-related histopathological changes in male hairless mouse skin. Toxicology, 2011, 282(3), 129-138.
[http://dx.doi.org/10.1016/j.tox.2011.01.021] [PMID: 21295104]
[41]
Jain, A.K.; Tewari-Singh, N.; Gu, M.; Inturi, S.; White, C.W.; Agarwal, R. Sulfur mustard analog, 2-chloroethyl ethyl sulfide-induced skin injury involves DNA damage and induction of inflammatory mediators, in part via oxidative stress, in SKH-1 hairless mouse skin. Toxicol. Lett., 2011, 205(3), 293-301.
[http://dx.doi.org/10.1016/j.toxlet.2011.06.019] [PMID: 21722719]
[42]
Tewari-Singh, N.; Agarwal, R. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure. Ann. N. Y. Acad. Sci., 2016, 1374(1), 184-192.
[http://dx.doi.org/10.1111/nyas.13099] [PMID: 27326543]
[43]
Tewari-Singh, N.; Jain, A.K.; Inturi, S.; Agarwal, C.; White, C.W.; Agarwal, R. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation. PLoS One, 2012, 7(9)e46149
[http://dx.doi.org/10.1371/journal.pone.0046149] [PMID: 23029417]
[44]
Khateri, S.; Balali-Mood, M.; Blain, P.; Williams, F.; Jowsey, P.; Soroush, M.R.; Behravan, E.; Sadeghi, M. DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure. Toxicol. Lett., 2018, 293, 67-72.
[http://dx.doi.org/10.1016/j.toxlet.2017.12.001] [PMID: 29217481]
[45]
Bakkenist, C.J.; Czambel, R.K.; Hershberger, P.A.; Tawbi, H.; Beumer, J.H.; Schmitz, J.C. A quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX Phosphorylation in human peripheral blood mononuclear cells. Oncoscience, 2015, 2(5), 542-554.
[http://dx.doi.org/10.18632/oncoscience.162] [PMID: 26097887]
[46]
Srivastava, N.N.; Shukla, S.K.; Yashavarddhan, M.H.; Devi, M.; Tripathi, R.P.; Gupta, M.L. Modification of radiation-induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: an in vitro study in human blood leukocytes. Environ. Mol. Mutagen., 2014, 55(5), 436-448.
[http://dx.doi.org/10.1002/em.21853] [PMID: 24500925]
[47]
Institute of Medicine Veterans at Risk.The Health Effects of Mustard Gas and Lewisite; Nat. Acad. Press: Washington, DC, 1993.
[48]
Shukla, S.K.; Sharma, A.K.; Gupta, V.; Kalonia, A.; Shaw, P. Challenges with wound infection models in drug development. Curr. Drug Targets, 2020, 21(13), 1301-1312.
[http://dx.doi.org/10.2174/1389450121666200302093312] [PMID: 32116189]
[49]
Young, S.B.; Setlow, P. Mechanisms of killing of Bacillus subtilis spores by hypochlorite and chlorine dioxide. J. Appl. Microbiol., 2003, 95(1), 54-67.
[http://dx.doi.org/10.1046/j.1365-2672.2003.01960.x] [PMID: 12807454]
[50]
Quan, Y.; Kim, H.Y.; Shin, I.S. Bactericidal activity of strong acidic hypochlorous water against Escherichia coli O157:H7 and Listeria monocytogenes in biofilms attached to stainless steel. Food Sci. Biotechnol., 2017, 26(3), 841-846.
[http://dx.doi.org/10.1007/s10068-017-0086-2] [PMID: 30263611]
[51]
Deza, M.A.; Araujo, M.; Garrido, M.J. Inactivation of Escherichia coli O157:H7, Salmonella enteritidis and Listeria monocytogenes on the surface of tomatoes by neutral electrolyzed water. Lett. Appl. Microbiol., 2003, 37(6), 482-487.
[http://dx.doi.org/10.1046/j.1472-765X.2003.01433.x] [PMID: 14633103]
[52]
Singh, S.S. Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr. Drug Metab., 2006, 7(2), 165-182.
[http://dx.doi.org/10.2174/138920006775541552] [PMID: 16472106]
[53]
Andrade, E.L.; Bento, A.F.; Cavalli, J.; Oliveira, S.K.; Schwanke, R.C.; Siqueira, J.M.; Freitas, C.S.; Marcon, R.; Calixto, J.B. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies. Braz. J. Med. Biol. Res., 2016, 49(12)e5646
[http://dx.doi.org/10.1590/1414-431x20165646] [PMID: 27982281]
[54]
Organization for Economic and Cooperative Development― OECD. Chlorine. CAS No. 7782-50-5. Cooperative chemicals assessment meeting (SIAM) 16, 27-30, screening information dataset,. 2003.
[55]
Zhang, B.; Zhong, Z.; Min, M.; Ding, K.; Xie, Q.; Ruan, R. Catalytic fast co-pyrolysis of biomass and food waste to produce aromatics: Analytical Py-GC/MS study. Bioresour. Technol., 2015, 189, 30-35.
[http://dx.doi.org/10.1016/j.biortech.2015.03.092] [PMID: 25864028]
[56]
Armstrong, D.G.; Bohn, G.; Glat, P.; Kavros, S.J.; Kirsner, R.; Snyder, R.; Tettelbach, W. Expert recommendations for the use of hypochlorous solution: science and clinical application. Ostomy Wound Manage., 2015, 61(5), S2-S19.
[PMID: 28692424]
[57]
Sarada, B.V.; Vijay, R.; Johnson, R.; Narasinga Rao, T.; Padmanabham, G. Fight Against COVID-19: ARCI’s Technologies for Disinfection. Trans. Indian Natl. Acad. Eng., 2020, 5, 349-354.
[http://dx.doi.org/10.1007/s41403-020-00153-3]
[58]
Del Rosso, J.Q.; Bhatia, N. Status report on topical hypochlorous acid: clinical relevance of specific formulations, potential modes of action, and study outcomes. J. Clin. Aesthet. Dermatol., 2018, 11(11), 36-39.
[PMID: 30588272]
[59]
Technology Evaluation Report. Decontamination of Sulfur Mustard and Thickened Sulfur Mustard Using Chlorine Dioxide Fumigation.. 2011.

Rights & Permissions Print Cite
Article Metrics
15
4
© 2025 Bentham Science Publishers | Privacy Policy