The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning

Balali-Mood, Mahdi; Hefazi, Mehrdad

doi:10.1111/j.1472-8206.2005.00325.x

Cited by 261 publications

(251 citation statements)

References 85 publications

(182 reference statements)

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“…However, the Iraqi use of SM in the 1985-1988 Iran-Iraq war prompted Iranian ophthalmologists to record the range of ocular injuries incurred by their exposed troops. [4][5][6][7][8][9][10][11][12] This has highlighted the global need for ocular therapies against SM exposure. Even after 100 years of study, there are still no U.S. Food and Drug Administration (FDA)-approved countermeasures against vesicant exposures, whether to the eye, skin, or lung.…”

mentioning

confidence: 99%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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Purpose: The goals of this study were (1) to compare the injury at the basement membrane zone (BMZ) of rabbit corneal organ cultures exposed to half mustard (2 chloroethyl ethyl sulfide, CEES) and nitrogen mustard with that of in vivo rabbit eyes exposed to sulfur mustard (SM); (2) to test the efficacy of 4 tetracycline derivatives in attenuating vesicant-induced BMZ disruption in the 24-h period postexposure; and (3) to use the most effective tetracycline derivative to compare the improvement of injury when the drug is delivered as drops or hydrogels to eyes exposed in vivo to SM. Methods: Histological analysis of hematoxylin and eosin-stained sections was performed; the ultrastructure of the corneal BMZ was evaluated by transmission electron microscopy; matrix metalloproteinase-9 was assessed by immunofluorescence; doxycycline as drops or a hydrogel was applied daily for 28 days to eyes exposed in vivo to SM. Corneal edema was assessed by pachymetry and the extent of neovascularization was graded by length of longest vessel in each quadrant. Results: Injury to the BMZ was highly similar with all vesicants, but varied in degree of severity. The effectiveness of the 4 drugs in retaining BMZ integrity did not correlate with their ability to attenuate matrix metalloproteinase-9 expression at the epithelial-stromal border. Doxycycline was most effective on organ cultures; therefore, it was applied as drops or a hydrogel to rabbit corneas exposed in vivo to SM. Eyes were examined at 1, 3, 7, and 28 days after exposure. At 7 and 28 days after SM exposure, eyes treated with doxycycline were greatly improved over those that received no therapy. Corneal thickness decreased somewhat faster using doxycycline drops, whereas the hydrogel formulation decreased the incidence of neovascularization. Conclusions: Corneal cultures exposed to 2-chloroethyl ethyl sulfide and nitrogen mustard were effective models to simulate in vivo SM exposures. Doxycycline as drops and hydrogels ameliorated vesicant injury. With in vivo exposed animals, the drops reduced edema faster than the hydrogels, but use of the hydrogels significantly reduced neovascularization. The data provide proof of principle that a hydrogel formulation of doxycycline as a daily therapy for ocular vesicant injury should be further investigated.

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confidence: 99%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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“…U íránských veteránů zasažených sirným yperitem byly zjištěny celkové počty leukocytů i méně než 200/µl (10,24). Nejcitlivější se zdá být populace NK buněk (natural killers), jejichž pokles vykazuje signifikantní změny i po 20 letech (8). Poškození imunitního systému se projevuje také na humorální úrovni.…”

Section: Systémové účInkyunclassified

“…U těžce exponovaných íránských veteránů byly nalezeny významně vyšší hodnoty IgM. Zvýšená hladina složek komplementu C3 a C4 byla zjištěna po dobu jednoho roku (8).…”

Section: Systémové účInkyunclassified

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Sulfur Mustard: Persisting Threat

Jost¹,

Múčková²,

Štětina³

et al. 2018

Mil. Med. Sci. Lett.

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“…Although SM can cause these different tissue effects, most mortality following SM exposure has been attributed to pulmonary damage and respiratory tract lesions. Respiratory complications of SM poisoning in Iranian veterans have included laryngitis, tracheobronchitis, bronchiolitis, bronchopneumonia, chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis (Bijani and Moghadamnia, 2002;Balali-Mood and Hefazi, 2005;Emad and Emad, 2007;Ghanei and Harandi, 2007). Since SM is a highly reactive chemical, its pathogenic mechanisms, e.g., DNA damage, are initiated without much delay but the tissue injury is not seen until after a lag period of 12 to 24 hours (Papirmeister et al, 1985;Rosenthal et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard–Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

Keyser

Andres

Nealley

et al. 2012

J Pharmacol Exp Ther

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Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent. Besides skin and eye injury, respiratory damage has been mainly responsible for morbidity and mortality after SM exposure. Previously, it was shown that suppressing the death receptor (DR) response by the dominant-negative Fas-associated death domain protein prior to SM exposure blocked apoptosis and microvesication in skin. Here, we studied whether antagonizing the Fas receptor (FasR) pathway by small-interfering RNA (siRNA) applied after SM exposure would prevent apoptosis and, thus, airway injury. Normal human bronchial/tracheal epithelial (NHBE) cells were used as an in vitro model with FasR siRNA, FasR agonistic antibody CH11, and FasR antagonistic antibody ZB4 as investigative tools. In NHBE cells, both SM (300 mM) and CH11 (100 ng/ml) induced caspase-3 activation, which was inhibited by FasR siRNA and ZB4, indicating that SM-induced apoptosis was via the Fas response. FasR siRNA inhibited SMinduced caspase-3 activation when added to NHBE cultures up to 8 hours after SM. Results using annexin V/propidium iodidestained cells showed that both apoptosis and necrosis were involved in cell death due to SM; FasR siRNA decreased both apoptotic and necrotic cell populations. Bronchoalveolar lavage fluid (BALF) of rats exposed to SM (1 mg/kg, 50 minutes) revealed a significant (P , 0.05) increase in soluble Fas ligand and active caspase-3 in BALF cells. These findings suggest an intervention of Fas-mediated apoptosis as a postexposure therapeutic strategy with a therapeutic window for SM inhalation injury and possibly other respiratory diseases involving the Fas response.

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The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning

Cited by 261 publications

References 85 publications

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Sulfur Mustard: Persisting Threat

Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard–Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

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