Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.
OBJECTIVE
Mustard agents are highly toxic and abundant warfare chemicals, primarily affecting ocular tissues, with no specific treatment antidote. The purpose of the present study was to examine the efficacy of novel metallocomplexes, known to inhibit the formation of highly reactive free radicals, to reduce ocular injury induced by nitrogen mustard (NM).


METHODS
One eye in each of 72 rabbits was exposed to 1% to 2% NM. Topical treatment with eye drops of a metallocomplex--either zinc- or gallium-desferrioxamine (Zn/DFO and Ga/DFO)--was compared with treatment with saline, zinc (chloride), or DFO alone. Examiners masked to the treatment groups assessed the extent of ocular injury and the response to treatment using clinical, histologic, and biochemical criteria.


RESULTS
Exposure to NM followed by administration of carrier alone (saline) caused severe and long-lasting injury to ocular anterior segment structures. Treatment with either Zn/DFO or Ga/DFO yielded marked protection (52%-64%), including faster healing of corneal epithelial erosions, less scarring and neovascularization, decreased inflammation in the anterior chamber, better maintenance of intraocular pressure, and less severe changes in the iris and lens. These were also associated with better preservation of systemic antioxidant status. Zinc or DFO alone afforded lower levels of protection. No toxic effects of these complexes were observed.


CONCLUSIONS
It is suggested that Zn/DFO or Ga/DFO, by virtue of their enhanced ability to infiltrate cells and inhibit transition metal-dependent formation of free radicals through the combined push-pull mechanism, be considered as a basis for treatment of mustard injuries.
Banin
Eyal
E
Department of Ophthalmology, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. banine@md.huji.ac.il
Morad
Yair
Y
Berenshtein
Eduard
E
Obolensky
Alexey
A
Yahalom
Claudia
C
Goldich
Jacob
J
Adibelli
Fatih M
FM
Zuniga
Gladys
G
DeAnda
Maribel
M
Pe'er
Jacob
J
Chevion
Mordechai
M
D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000473:pathology; D002057:Burns, Chemical / Q000188:drug therapy* / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004596:Electroretinography; D005126:Eye Burns / Q000139:chemically induced* / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D005708:Gallium; D007429:Intraocular Pressure; D008466:Mechlorethamine / Q000633:toxicity*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D017967:Zinc Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D002619:Chemical Warfare Agents; D005609:Free Radicals; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; D008466:Mechlorethamine; D005708:Gallium; D003676:Deferoxamine