Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea
Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea
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DOI：
10.1016/j.toxlet.2017.11.026
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Agarwal, Rajesh
中科院分区：
文献类型：
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作者：
Goswami, Dinesh G.;Kant, Rama;Agarwal, Rajesh
发泡剂硫芥（SM）对眼睛造成毁灭性伤害；然而，目前还没有有效的解毒剂。我们利用SM双功能类似物氮芥（NM），在离体兔角膜器官培养模型中发现NM诱导的角膜损伤与SM所报道的角膜损伤相似。通过该模型，我们证明了地塞米松（DEX）、强力霉素（DOX）和水飞蓟宾（SB）在冲洗NM后立即添加地塞米松（DEX）、强力霉素（DOX）和水飞蓟宾（SB）在逆转NM（暴露2小时）引起的角膜损伤方面的治疗效果。在本研究中，我们进一步研究了在NM暴露2小时后立即、2小时或4小时添加类似/更高剂量的这些制剂的效果。在暴露于纳米2小时后立即添加或洗涤纳米2小时后，所有三种治疗药物均可逆转已建立的纳米诱导损伤生物标志物；然而，当洗涤NM后4小时进行处理时，效果不显著。总之，我们的结果进一步显示了这些药物在逆转纳米诱导的角膜损伤方面的有益作用，并指出了有效治疗的时间窗口。这可能有助于未来开发针对泡泡剂引起的眼部损伤的靶向治疗方法。
Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2 h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4 h after washing NM following its 2 h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2 h after washing NM following its 2 h exposure; however, when treatments were carried out 4 h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury.