In vivo inhibition of 1-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide
In vivo inhibition of 1-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide
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DOI：
10.1016/j.freeradbiomed.2010.12.017
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发表时间：
2011-03-15
影响因子：
7.4
通讯作者：
Ercal, Nuran
中科院分区：
文献类型：
--
作者：
Carey, Joshua W.;Pinarci, Eylem Y.;Ercal, Nuran
观察了自由基清除剂N-乙酰半胱氨酸酰胺(NACA)对Wistar大鼠白内障形成的影响。用谷胱甘肽(GSH)合成抑制剂L-丁硫氨酸-(S，R)-亚磺胺(BSO)诱导大鼠白内障形成。为了评估NACA对BSO诱导的白内障是否有显著影响，将大鼠分为四组：(1)对照组，(2)仅BSO组，(3)仅NACA组，(4)NACA+BSO组。对照组在产后第3天ip生理盐水，单纯BSO组ip BSO(4 mmol/kg体重)，NACA组仅ip NACA(250 mg/kg体重)，NACA+BSO组在注射BSO前30min注射NACA。产后第15天处死幼鼠，在裂隙灯显微镜下进行检查。分析了他们的晶状体的选择性氧化应激参数，包括还原型和氧化型谷胱甘肽、蛋白质羰基、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和丙二醛。对照组和NACA组的幼鼠晶状体都是清晰的，而BSO组的所有幼鼠都出现了明确的白内障。研究发现，在BSO治疗期间补充NACA可以防止NACA+BSO组大鼠大部分幼鼠白内障的形成。这些幼崽中只有20%患上了白内障，其余的保留了清晰的晶状体。此外，BSO单独治疗组的GSH水平显著降低，但在BSO治疗期间接受NACA注射的大鼠GSH水平得到补充。我们的发现表明，NACA通过限制蛋白质羰化、脂质过氧化和氧化还原系统成分以及补充抗氧化酶来抑制白内障的形成。(C)2010 Elsevier Inc.保留所有权利。
The effects effects of N-acetylcysteine amide (NACA), a free radical scavenger, on cataract development were evaluated in Wistar rat pups. Cataract formation was induced in these animals with an intraperitoneal injection of a glutathione (GSH) synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). To assess whether NACA has a significant impact on BSO-induced cataracts, the rats were divided into four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA + BSO. The control group received only saline ip injections on postpartum day 3, the BSO-only group was given ip injections of BSO (4 mmol/kg body wt), the NACA-only group received ip injections of only NACA (250 mg/kg body wt), and the NACA + BSO group was given a dose of NACA 30 min before administration of the BSO injection. The pups were sacrificed on postpartum day 15, after examination under a slit-lamp microscope. Their lenses were analyzed for selective oxidative stress parameters, including glutathione (reduced and oxidized), protein carbonyls, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. The lenses of pups in both the control and the NACA-only groups were clear, whereas all pups within the BSO-only group developed well-defined cataracts. It was found that supplemental NACA injections during BSO treatment prevented cataract formation in most of the rat pups in the NACA + BSO group. Only 20% of these pups developed cataracts, and the rest retained clear lenses. Further, GSH levels were significantly decreased in the BSO-only treated group, but rats that received NACA injections during BSO treatment had these levels of GSH replenished. Our findings indicate that NACA inhibits cataract formation by limiting protein carbonylation, lipid peroxidation, and redox system components, as well as replenishing antioxidant enzymes. (C) 2010 Elsevier Inc. All rights reserved.