Injury induced by chemical warfare agents: Characterization and treatment of ocular tissues exposed to nitrogen mustard
Injury induced by chemical warfare agents: Characterization and treatment of ocular tissues exposed to nitrogen mustard
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DOI：
10.1167/iovs.02-1164
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发表时间：
2003-07-01
影响因子：
4.4
通讯作者：
Chevion, M
中科院分区：
文献类型：
--
作者：
Banin, E;Morad, Y;Chevion, M
目的.芥子气制剂是剧毒和大量的战争化学品，主要影响眼组织，没有特定的治疗解毒剂。本研究的目的是检查新型金属配合物的有效性，已知抑制高活性自由基的形成，以减少氮芥（NM）诱导的眼损伤。将72只家兔的每只眼睛暴露于1%至2%的NM。用金属络合物-锌-或镓-去铁胺（Zn/DFO和Ga/DFO）的滴眼剂的局部治疗与用盐水、锌（氯化物）或单独DFO的治疗进行比较。检查者对治疗组不知情，使用临床、组织学和生化标准评估眼损伤程度和对治疗的反应。暴露于NM后单独给予载体（盐水）对眼前段结构造成严重和持久的损伤。用Zn/DFO或Ga/DFO治疗产生了显著的保护作用（52%-64%），包括角膜上皮糜烂愈合更快、瘢痕形成和新血管形成更少、前房炎症减少、眼内压维持更好以及虹膜和透镜变化不太严重。这些也与更好地保持全身抗氧化状态有关。锌或DFO单独提供较低水平的保护。结论：这些配合物均无毒性作用。提示Zn/DFO或Ga/DFO通过推拉结合机制增强细胞浸润能力和抑制过渡金属依赖性自由基形成，可作为芥子气损伤治疗的基础。（Invest Ophthalmol维斯科学。2003;44：2966-2972）DOI：10.1167/iovs.02-1164。
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. (Invest Ophthalmol Vis Sci. 2003;44: 2966-2972) DOI:10.1167/iovs.02-1164.