TY - JOUR
T1 - Injury induced by chemical warfare agents
T2 - Characterization and treatment of ocular tissues exposed to nitrogen mustard
AU - Banin, Eyal
AU - Morad, Yair
AU - Berenshtein, Eduard
AU - Obolensky, Alexey
AU - Yahalom, Claudia
AU - Goldich, Jacob
AU - Adibelli, Fatih M.
AU - Zuniga, Gladys
AU - DeAnda, Maribel
AU - Pe'er, Jacob
AU - Chevion, Mordechai
PY - 2003/7/1
Y1 - 2003/7/1
N2 - PURPOSE. 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.
AB - PURPOSE. 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.
UR - http://www.scopus.com/inward/record.url?scp=0038238209&partnerID=8YFLogxK
U2 - 10.1167/iovs.02-1164
DO - 10.1167/iovs.02-1164
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C2 - 12824239
AN - SCOPUS:0038238209
SN - 0146-0404
VL - 44
SP - 2966
EP - 2972
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 7
ER -