Sulfur Mustard Toxicity of the Rabbit Eye: An Ultrastructural Study

Petrali, John P.; Miskena, F. J.; Hamilton, Tracey A.; Finger, A.V.; Janny, Stephen J.

doi:10.3109/15569529709048901

Cited by 12 publications

(6 citation statements)

References 3 publications

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“…This is characterized by a thickening of the epithelium, largely due to epithelial hyperplasia, and localized separation of the epithelium from the basement membrane zone. These data are consistent with the effects of UVB or sulfur mustard on rabbit cornea in vivo ( Petrali et al, 1997; Cejka et al, 2010) and demonstrate the utility of the cornea organ culture model for mechanistic studies on the action of xenobiotics.…”

Section: Discussionsupporting

confidence: 75%

“…Depending on dose, inflammation and edema are observed as well as increasing corneal thickness, and sloughing of epithelial cells. Detachment of epithelial cells is thought to be due to degradation of the basement membrane and basal cell hemidesmosome transmembraneous components, which are critical for the attachment of the epithelium to the basement membrane (Petrali et al , 1997; McNutt et al , 2012; Kadar et al , 2013). Our laboratories have been characterizing the effects of ocular toxicants including UVB and vesicants on rabbit cornea using an air-lifted organ culture model (Gordon et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

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The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard

Zheng

Mishin

et al. 2013

Toxicology and Applied Pharmacology

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The cornea is highly sensitive to oxidative stress, a process that can lead to lipid peroxidation. Ultraviolet light B (UVB) and nitrogen mustard (mechlorethamine) are corneal toxicants known to induce oxidative stress. Using a rabbit air-lifted corneal organ culture model, the oxidative stress responses to these toxicants in the corneal epithelium was characterized. Treatment of the cornea with UVB (0.5 J/cm2) or nitrogen mustard (100 nmol) resulted in the generation of 4-hydroxynonenal (4-HNE), a reactive lipid peroxidation end product. This was associated with increased expression of the antioxidant, heme oxygenase-1 (HO-1). In human corneal epithelial cells in culture, addition of 4-HNE or 9-nitrooleic acid, a reactive nitrolipid formed during nitrosative stress, caused a time-dependent induction of HO-1 mRNA and protein; maximal responses were evident after 10 hr with 30 μM 4-HNE or 6 hr with 10 μM 9-nitrooleic acid. 4-HNE and 9-nitrooleic acid were also found to activate Erk1/2, JNK and p38 MAP kinases, as well as phosphoinositide-3-kinase (PI3)/Akt. Inhibition of p38 blocked 4-HNE- and 9-nitrooleic acid-induced HO-1 expression. Inhibition of Erk1/2, and to a lesser extent, JNK and PI3K/Akt, suppressed only 4-HNE-induced HO-1, while inhibition of JNK and PI3K/Akt, but not Erk1/2, partly reduced 9-nitrooleic acid-induced HO-1. These data indicate that the actions of 4-HNE and 9-nitrooleic acid on corneal epithelial cells are distinct. The sensitivity of corneal epithelial cells to oxidative stress may be an important mechanism mediating tissue injury induced by UVB or nitrogen mustard.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard

Zheng

Mishin

et al. 2013

Toxicology and Applied Pharmacology

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“…In some previous studies indeed an insult was inflicted to only one eye while the other served as control. 20 However our study was a long-term study, which should also mimic the possible interaction between the two eyes. Moreover, the majority of victims exposed to HD during WWI and during the Iran-Iraq conflict suffered ocular lesions in both eyes.…”

Section: Discussionmentioning

confidence: 99%

“…The continuing threat of HD potential use has led to augmented research efforts to develop effective treatments for HDinduced injuries. [19][20] The sequence of events following HD intoxication was thought until recently to be composed of cytotoxic events, followed by tissue inflammation. 1 Recent evidence showed that HD can induce release of primary inflammatory mediators by its direct action on cells, [21][22] thus inflammation can be induced prior to cell death.…”

Section: Introductionmentioning

confidence: 99%

Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits

Kadar

Turetz²,

Fishbine³

et al. 2001

Current Eye Research

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“…Different studies have been performed on the acute and delayed onsets of ocular lesion induced by SM toxicity on the rabbit eye and the treatment options [Mann and Pullinger, 1942;Williams and Bhattacherjee, 1984;Amir et al, 2000;Kadar et al, 2001Kadar et al, , 2013aKadar et al, , 2014Amir et al, 2003;Petrali et al, 2008;Nie et al, 2014]. In 1940s, Mann and Pullinger; Livingston and Walker observed ocular effects of SM in laboratory rabbits and discussed the treatment options [Mann and Pullinger, 1942;Williams and Bhattacherjee, 1984].…”

Section: Animal Studies On Sm-induced Ocular Symptoms and Treatment Omentioning

confidence: 99%

Ocular Effects of Sulfur Mustard and Therapeutic Approaches

Panahi

Rajaee

Sahebkar

2017

J of Cellular Biochemistry

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Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes, and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis, and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication, and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD), and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation, and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin, and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. J. Cell. Biochem. 118: 3549-3560, 2017. © 2017 Wiley Periodicals, Inc.

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Sulfur Mustard Toxicity of the Rabbit Eye: An Ultrastructural Study

Cited by 12 publications

References 3 publications

The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard

The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard

Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits

Ocular Effects of Sulfur Mustard and Therapeutic Approaches

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