Detoxification of the Toxic Sulfur Mustard Simulant by a Supramolecular Antidote in Vitro and in Vivo

2021 ◽  
Author(s):  
Siyuan Zhou ◽  
Wangzi Li ◽  
Qi Zhao ◽  
Hongqiang Dong ◽  
Yueqi Wang ◽  
...  
Keyword(s):  
Sulfur Mustard

scholarly journals Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor Paromov ◽  
Sudha Kumari ◽  
Marianne Brannon ◽  
Naga S. Kanaparthy ◽  
Hongsong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Sulfur Mustard ◽  
Alkylating Agents ◽  
Water Soluble ◽  
Model Systems ◽  
Mustard Gas

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated usingin vitromodel systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously describedin vivoprotective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

Evaluation of decontamination efficacy of electrolytically generated hypochlorous acid for vesicating agent: A multimodel Study

2021 ◽  
Vol 22 ◽  
Author(s):  
Ajay Kumar Sharma ◽  
Sandeep Kumar Shukla ◽  
Aman Kalonia ◽  
Priyanka Shaw ◽  
Kushagra Khanna ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hypochlorous Acid ◽  
Sulfur Mustard ◽  
Uv Spectroscopy ◽  
In Vivo Studies ◽  
Histopathological Study ◽  
Blister Formation ◽  
Oxidizing Agents

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 perfomred in Strain A and immune compromised mice by subcutaneous as well as prophylactic topical administrion 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 has been carried out in human blood using flow cytometry. Anti-bacterial action was tested by employing broth micro dilution methods. 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 flourences 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 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.

Protective Effects of Amifostine and Its Analogues on Sulfur Mustard Toxicity in Vitro and in Vivo

2001 ◽  
Vol 176 (1) ◽  
pp. 24-33 ◽  
Author(s):  
R. Bhattacharya ◽  
P.V. Lakshmana Rao ◽  
S.C. Pant ◽  
Pravin Kumar ◽  
R.K. Tulsawani ◽  
...  
Keyword(s):  
Sulfur Mustard ◽  
Protective Effects ◽  
Toxicity In Vitro

Monitoring of in Vitro and in Vivo Exposure to Sulfur Mustard by GC/MS Determination of the N-Terminal Valine Adduct in Hemoglobin after a Modified Edman Degradation

1996 ◽  
Vol 9 (4) ◽  
pp. 788-792 ◽  
Author(s):  
Alex Fidder ◽  
Daan Noort ◽  
Ad L. de Jong ◽  
Hendrik C. Trap ◽  
Leo P. A. de Jong ◽  
...  
Keyword(s):  
Sulfur Mustard ◽  
Edman Degradation

A facile methodology for the synthesis and detection of N7-guanine adduct of sulfur mustard as a biomarker

2002 ◽  
Vol 80 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Mula Kameswara Rao ◽  
Pinaki S Bhadury ◽  
Mamta Sharma ◽  
Rajinder S Dangi ◽  
Appanabhotla S Bhaskar ◽  
...  
Keyword(s):  
Physical Properties ◽  
Spectral Data ◽  
Convenient Method ◽  
Sulfur Mustard ◽  
2D Nmr ◽  
High Yields

A simple and convenient method has been developed for the synthesis of a N7-guanine adduct of sulfur mustard (SM), which can serve as an efficient biomarker for alleged exposure to SM. The adduct obtained in high yields (~78%) was characterized on the basis of its physical properties and spectral data. In addition, HPLC and LC-MS conditions have been standardized for the detection of the adduct in both in vitro and in vivo samples, which is useful for retrospective detection of exposure to SM in biological samples.Key words: sulfur mustard, biomarker, N7-guanine adduct, in vitro, in vivo, HPLC, LC-MS, electrospray, 2D NMR.

Morphological effects of sulfur mustard on a human skin equivalent

1991 ◽  
Vol 49 ◽  
pp. 78-79
Author(s):  
J.P. Petrali ◽  
S.B. Oglesby ◽  
T.A. Justus
Keyword(s):  
Human Skin ◽  
Sulfur Mustard ◽  
Athymic Nude Mouse ◽  
Skin Equivalent ◽  
Model Systems ◽  
Cells In Culture ◽  
Vitro Model ◽  
Human Skin Equivalent

We have previously reported morphological correlates of sulfur mustard (HD) toxicity in several model systems: the human skin grafted athymic nude mouse; the hairless guinea pig; and human cells in culture. We are now describing HD effects in a human skin equivalent, TESTSKIN®, and comparing these effects with those already reported for animal models and cells in culture. The human skin equivalent (HSE) is used here as an organotypic in vitro model system to bridge the knowledge gap between HD effects in monotypic cells in culture and animal in vivo effects. Additionally, HSE allowed study of HD toxicity which circumvented the concern of using human biopsied tissue.

Ultrastructural characterization of an in vitro model of human epidermis: its potential for sulfur mustard study

1995 ◽  
Vol 53 ◽  
pp. 1004-1005
Author(s):  
J.P. Petrali ◽  
P.T. Lopolito ◽  
T.A. Hamilton ◽  
S.B. Oglesby-Megee ◽  
L.S. Rhoads
Keyword(s):  
Human Skin ◽  
Sulfur Mustard ◽  
Cellular Models ◽  
Skin Equivalents ◽  
Information Gap ◽  
Ultrastructural Characterization ◽  
Vitro Model ◽  
Membrane Components

Morphological correlates of sulfur mustard toxicity continue to be studied in in vivo models such as the haired and hairless guinea pig and the domestic weanling pig. These animal models provide useful evidence for the mechanisms of sulfur mustard-induced lesions, however the correlation with human skin is not exact and the availability of a continuing supply of any animal model is problematic. In vitro studies have largely been performed with cultured monotypic human cells such keratinocytes and lymphocytes. Although monotypic cellular models have added data to the mechanisms of the observed cytopathology, the acclimatized nature of media-nourished cells may present a different phenotype for study than in vivo. To bridge the information gap between monolayers of cells and in vivo studies, in vitro skin equivalents have been proposed as suitable models. We have used several commercially available human skin equivalents in the past, however the lack of basement membrane components, the absence or paucity of hemidesmosomes, general problems with replication and inconsistences of availability, question the usefulness of commercial preparations at this time.

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