Treatment of ocular tissues exposed to nitrogen mustard: beneficial effect of zinc desferrioxamine combined with steroids.
OBJECTIVE
Exposure of the ocular surface to mustard gas chemical warfare leads to a destructive inflammatory reaction. Both steroids and a novel metalocomplex free radical scavenger, zinc desferrioxamine (Zn/DFO), have been shown to be effective separately in reducing ocular damage. The purpose of the present study was to investigate whether the effectiveness of both medications applied simultaneously is superior to the effectiveness of either one applied alone.


METHODS
One eye in each of 52 rabbits was exposed to 2% nitrogen mustard (NM). Topical treatment with eye drops of a metal complex-zinc desferrioxamine (Zn/DFO)-combined with dexamethasone phosphate (0.1%), was compared with the administration of saline or treatment with Zn/DFO or dexamethasone alone. Eight eyes (four animals) that were not exposed to NM served as the control. Examiners masked to the treatment groups assessed the extent of ocular injury and the response to treatment using clinical, histologic, and biochemical criteria.


RESULTS
Treatment with the combination of Zn/DFO and dexamethasone was significantly more effective than was dexamethasone or Zn/DFO alone in reducing NM injury to ocular anterior segment structures. In combination-treated eyes, corneal re-epithelization was faster, corneal neovascularization was less severe, and intraocular pressure was not as severely elevated as in the saline or the Zn/DFO- or dexamethasone-alone groups. In addition, systemic antioxidant status was better conserved in the combination-treated animals.


CONCLUSIONS
The findings suggest that the combination of topically applied Zn/DFO and dexamethasone, by virtue of their additive inhibitory effects on free radical formation and inflammation, should be considered as a basis for the treatment of ocular mustard gas injuries.
Morad
Yair
Y
Department of Ophthalmology, Assaf Harofeh Medical Center, Zrifin 73000, Israel. ymorad@013.net.il
Banin
Eyal
E
Averbukh
Edward
E
Berenshtein
Eduard
E
Obolensky
Alexey
A
Chevion
Mordechai
M
D000818:Animals; D001284:Atrophy; D002057:Burns, Chemical / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003316:Corneal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003318:Corneal Opacity / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005126:Eye Burns / Q000139:chemically induced* / Q000473:pathology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D007429:Intraocular Pressure; D007498:Iris / Q000473:pathology; D008466:Mechlorethamine / Q000633:toxicity*; D051150:Methionine Sulfoxide Reductases; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010088:Oxidoreductases / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects; D015032:Zinc
D002619:Chemical Warfare Agents; D016166:Free Radical Scavengers; D005938:Glucocorticoids; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C086228:zinc-desferrioxamine; D008466:Mechlorethamine; D003907:Dexamethasone; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D003676:Deferoxamine; D015032:Zinc