原儿茶酸,一种亲电化合物,在氧化应激和光诱导的视网膜变性模型中的保护作用。

Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration.

机构信息

Del E Web Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.

出版信息

Invest Ophthalmol Vis Sci. 2012 Nov 27;53(12):7847-54. doi: 10.1167/iovs.12-10793.

Abstract

PURPOSE

The herb rosemary has been reported to have antioxidant and anti-inflammatory activity. We have previously shown that carnosic acid (CA), present in rosemary extract, crosses the blood-brain barrier to exert neuroprotective effects by upregulating endogenous antioxidant enzymes via the Nrf2 transcriptional pathway. Here we investigated the antioxidant and neuroprotective activity of CA in retinal cell lines exposed to oxidative stress and in a rat model of light-induced retinal degeneration (LIRD).

METHODS

Retina-derived cell lines ARPE-19 and 661W treated with hydrogen peroxide were used as in vitro models for testing the protective activity of CA. For in vivo testing, dark-adapted rats were given intraperitoneal injections of CA prior to exposure to white light to assess protection of the photoreceptor cells. Retinal damage was assessed by measuring outer nuclear layer thickness and by electroretinogram (ERG).

RESULTS

In vitro, CA significantly protected retina-derived cell lines (ARPE-19 and 661W) against H(2)O(2)-induced toxicity. CA induced antioxidant phase 2 enzymes and reduced formation of hyperoxidized peroxiredoxin (Prx)2. Similarly, we found that CA protected retinas in vivo from LIRD, producing significant improvement in outer nuclear layer thickness and ERG activity.

CONCLUSIONS

These findings suggest that CA may potentially have clinical application to diseases affecting the outer retina, including age-related macular degeneration and retinitis pigmentosa, in which oxidative stress is thought to contribute to disease progression.

摘要

目的

迷迭香具有抗氧化和抗炎活性。我们之前已经表明,迷迭香提取物中的鼠尾草酸(CA)通过 Nrf2 转录途径上调内源性抗氧化酶来发挥神经保护作用,从而穿过血脑屏障。在这里,我们研究了 CA 在暴露于氧化应激的视网膜细胞系和光诱导的视网膜变性(LIRD)大鼠模型中的抗氧化和神经保护活性。

方法

用过氧化氢处理的视网膜衍生细胞系 ARPE-19 和 661W 被用作测试 CA 保护活性的体外模型。为了进行体内测试,将暗适应的大鼠腹腔内注射 CA,然后暴露于白光下,以评估对光感受器细胞的保护作用。通过测量外核层厚度和视网膜电图(ERG)来评估视网膜损伤。

结果

在体外,CA 显著保护视网膜衍生细胞系(ARPE-19 和 661W)免受 H2O2 诱导的毒性。CA 诱导抗氧化第二阶段酶并减少过氧化物酶(Prx)2 的超氧化形成。同样,我们发现 CA 可以保护体内的 LIRD 视网膜,在外核层厚度和 ERG 活性方面均有显著改善。

结论

这些发现表明,CA 可能具有临床应用于影响外视网膜的疾病的潜力,包括年龄相关性黄斑变性和色素性视网膜炎,其中氧化应激被认为是疾病进展的原因。

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