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Melanin precursor 5,6-dihydroxyindol: protective effects and cytotoxicity on retinal cells in vitro and in vivo.

机译:黑色素前体5,6-二羟基吲哚:在体外和体内对视网膜细胞的保护作用和细胞毒性。

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摘要

5,6-dihydroxyindole (DHI) is a melanin pigment precursor with antioxidant properties. In the light of a report about cytotoxicity of DHI, the aim of this study was to assess possible toxic effects of DHI on cells related to the eye, such as human ARPE-19 cells and mouse retinal explants. Moreover, DHI was tested on its effects on retinal function in vivo using electroretinography. We found cytotoxicity of DHI against ARPE-19 cells at 100 microM, but not at 10 microM. 10 microM DHI exhibited a slight, though not significant protective activity against UV-A damage in ARPE-19 cells. We found cytoprotection in cultured mouse retinas by 50 microM DHI or its diacetylated derivative 5,6-diacetoxyindole (DAI), respectively. In ERG measurements in vivo, amplitudes were decreased only slightly by 100 microM DHI compared to saline, whereas a better preservation of amplitudes was visible at 10 microM DHI, in particular with respect to cones. In histological sections, more cones were found at 10 microM DHI than at 100 microM DHI. As a conclusion, DHI shows a slight protective effect at 10 microM both in vitro and in vivo. At 100 microM, it shows a strong cytotoxicity in vitro, which is strongly reduced in vivo.
机译:5,6-二羟基吲哚(DHI)是具有抗氧化性能的黑色素颜料前体。根据有关DHI的细胞毒性的报道,本研究的目的是评估DHI对与眼睛相关的细胞(例如人ARPE-19细胞和小鼠视网膜外植体)可能产生的毒性作用。此外,使用视网膜电图检查了DHI对体内视网膜功能的影响。我们发现DHI对ARPE-19细胞的细胞毒性为100 microM,而不是10 microM。 10 microM DHI对ARPE-19细胞中的UV-A损伤表现出轻微的保护作用,尽管不明显。我们发现50 microM DHI或其二乙酰化衍生物5,6-二乙酰氧基吲哚(DAI)分别对培养的小鼠视网膜具有细胞保护作用。在体内的ERG测量中,与盐水相比,振幅仅微降低了100 microM DHI,而在10 microM DHI上,尤其是对于视锥细胞,振幅的保持更好。在组织学切片中,在10 microM DHI处比在100 microM DHI处发现更多的视锥细胞。结论是,DHI在体外和体内在10 microM时均显示出轻微的保护作用。在100 microM时,它在体外显示出很强的细胞毒性,而在体内则大大降低了。

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