J Appl Biomed 17:136-145, 2019 | DOI: 10.32725/jab.2019.009

Screening of the chemoprotective effect of 13 compounds and their mixtures with sodium 2-mercaptoethanesulfonate against 2-chloroethyl ethyl sulfide

Petr Jost, Jaroslav Pejchal *, Tomas Kucera, Lubica Muckova, Rudolf Stetina
University of Defense, Faculty of Military Health Sciences, Department of Toxicology and Military Pharmacy, Hradec Králové, Czech Republic

2-chloroethyl ethyl sulfide (CEES) is a vesicant agent, commonly referred to half mustard due to its ability to form monofunctional adducts with DNA. In this study, we evaluated the chemoprotective potential of 13 compounds and their mixtures with sodium 2-mercaptoethanesulfonate (MESNA) against CEES-induced geno- and cytotoxicity in human lung cell line A-549. MESNA, L-glutathione (GSH), thiourea, sodium thiosulfate, hexamethylenetetramine, 4-acetamidophenol, asoxime dichloride (HI-6), N-acetyl-L-cysteine (NAC), sodium pyruvate, myo-inositol, 3-aminobenzamide (3-AB), nicotinamide, and Nω-nitro-L-arginine methyl ester hydrochloride and combinations of these compounds with MESNA were applied 30 min before CEES. DNA alkylation was measured using modified comet assay 1 and 24 h after the exposure. Cell viability was determined using MTT assay at 24 and 72 h. The mono-therapeutical approach identified MESNA and GSH to provide significant chemoprotection. NAC and 3-AB supported DNA damage repair, while cell viability remained unaffected. Mixtures of GSH or NAC with MESNA showed protective synergism against DNA damage. Other compounds or their combinations with MESNA failed due to the potentiation of CEES-induced cytotoxicity. The chemoprotection against CEES remains limited; however, the combination of substances can provide protective synergy and may represent a promising strategy in the treatment of accidental exposure to monoalkylating agents.

Keywords: 2-chloroethyl ethyl sulfide; A-549 cell line; chemoprotection; comet assay; MESNA; MTT assay
Grants and funding:

The work was supported by the grant of The Ministry of Education, Youth and Sports of the Czech Republic No. SV/ FVZ20127 and long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defense.

Conflicts of interest:

The authors declare that they have no conflict of interest.

Received: December 6, 2017; Accepted: June 3, 2019; Prepublished online: June 17, 2019; Published: June 28, 2019  Show citation

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Jost P, Pejchal J, Kucera T, Muckova L, Stetina R. Screening of the chemoprotective effect of 13 compounds and their mixtures with sodium 2-mercaptoethanesulfonate against 2-chloroethyl ethyl sulfide. J Appl Biomed. 2019;17(2):136-145. doi: 10.32725/jab.2019.009. PubMed PMID: 34907735.
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