Cytoprotectieve effects of rebamipide and carteolol hydrochloride against ultraviolet B-induced corneal damage in mice

Cytoprotectieve effects of rebamipide and carteolol hydrochloride against ultraviolet B-induced corneal damage in mice
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DOI:
10.1167/iovs.02-1043
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发表时间:
2003-07-01
影响因子:
4.4
通讯作者:
Ohira, A
Ohira, A
中科院分区:
医学2区
文献类型:
--
作者:
Tanito, M;Takanashi, T;Ohira, A

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目的.比较瑞巴派特(rebamipide,REB)和盐酸卡替洛尔(carteolol hydrochloride,CH)对UVB诱导的小鼠角膜损伤的保护作用。用RE B(1和10 mM)或CH(1、10和100 mM)局部预处理的BALB/c小鼠暴露于416 μ W/cm(2)的紫外(UV)B光。为了评估角膜损伤,对角膜混浊不规则性进行分级,并使用数字化角膜图像估计haze指数。通过使用8-羟基-2-脱氧鸟苷(80 HdG指数)的定量免疫组织化学来估计UVB暴露导致的角膜上皮中氧化DNA的形成。为探讨REB和CH对UVB诱导的细胞损伤的保护作用机制,采用分光光度法测定了REB和CH的紫外吸收光谱,并采用电子自旋共振(ESR)自旋捕集技术结合芬顿体系产生羟自由基的方法评价了它们对羟自由基的清除作用。UVB照射后72小时,用10 mM UVB预处理的小鼠的沼泽不规则性的严重程度、混浊指数和80 HdG指数显著降低,(分别为P < 0.05、P < 0.05和P < 0.01)01和P <0.01)和IOOmM(分别为P <0.01、P < 0.01和P < 0.01)的CH与用媒介物处理的小鼠相比。REB的吸收光谱与UVB波长重叠,CH的吸收光谱部分重叠。加入REB或CH后,对应于羟基自由基的ESR自旋信号降低。REB和CH减轻UVB诱导的角膜损伤,这可能是部分负责其防晒和清除羟基自由基的作用。(Invest Ophthalmol维斯科学。2003;44:2980-2985)DOI:10.1167/iovs-02-1043。
PURPOSE. To analyze whether rebamipide (REB) and carteolol hydrochloride (CH) protect against UVB-induced corneal damage in mice.METHODS. BALB/c mice topically pretreated with REB (1 and 10 mM) or CH (1, 10, and 100 mM) were exposed to ultraviolet (UV) B light at 416 muW/cm(2). To evaluate corneal damage, mire irregularity was graded, and the haze index was estimated by using digitized corneal images. The formation of oxidized DNA in the corneal epithelium resulting from UVB exposure was estimated by using quantitative immunohistochemistry for 8-hydroxy-2-deoxyguanosine (80HdG index). To analyze the mechanism of cytoprotection by REB and CH against UVB-induced cell damage, the UV absorption spectrum in these agents was evaluated by spectrophotometry, and their hydroxyl radical scavenging effect was evaluated by the electron spin resonance (ESR) spin trapping technique with Fenton system hydroxy radical generation.RESULTS. Seventy-two hours after UVB exposure, the severity of mire irregularity, haze index, and 80HdG index were significantly lower in mice pretreated with 10 mM (P < 0.05, P < 0.05, and P < 0.01, respectively) of REB and in mice pretreated with 10 mM (P < 0.05, P < 0.01, and P < 0.01, respectively) and 100 mM (P < 0.01, P < 0.01, and P < 0.01, respectively) of CH compared with mice treated with vehicle. The absorption spectrum of REB overlapped with the UVB wavelength, and that of CH overlapped partially. The ESR spin signal corresponding to the hydroxyl radical was reduced by the addition of REB or CH.CONCLUSIONS. REB and CH attenuate UVB-induced corneal damage, which may be partly responsible for their sunscreening and hydroxyl radical scavenging effects. (Invest Ophthalmol Vis Sci. 2003;44:2980-2985) DOI: 10.1167/iovs-02-1043.