Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Biochem Pharmacol. 2010 Oct 15;80(8):1260-5. doi: 10.1016/j.bcp.2010.06.027. Epub 2010 Jun 25.
Oxidant damage from reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major contributor to the cellular damage seen in numerous types of renal injury. Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found naturally in many common food sources. The anti-oxidant properties of resveratrol are of particular interest because of the fundamental role that oxidant damage plays in numerous forms of kidney injury. To examine whether resveratrol could block damage to the renal epithelial cell line, mIMCD-3, cells were exposed to the peroxynitrite donor 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1). Resveratrol produced a concentration-dependent inhibition of cytotoxicity induced by SIN-1. To examine the mechanism of protection, resveratrol was incubated with authentic peroxynitrite and found to block nitration of bovine serum albumin with an EC(50) value of 22.7 microM, in contrast to the known RNS scavenger, N-acetyl-l-cysteine, which inhibited nitration with an EC(50) value of 439 microM. These data suggested that resveratrol could provide functional protection by directly scavenging peroxynitrite. To examine whether resveratrol was a substrate for peroxynitrite oxidation, resveratrol was reacted with authentic peroxynitrite. Resveratrol nitration products and dimers were detected using liquid chromatograph with tandem electrospray mass spectrometry. Similar products were detected in the media of cells treated with SIN-1 and resveratrol. Taken collectively, the data suggest that resveratrol is able to provide functional protection of renal tubular cells, at least in part, by directly scavenging the RNS peroxynitrite. This property of resveratrol may contribute to the understanding of its anti-oxidant activities.
活性氧（ROS）和活性氮（RNS）引起的氧化剂损伤是多种类型肾损伤中细胞损伤的主要原因。白藜芦醇（反式-3,4',5-三羟基二苯乙烯）是一种植物抗毒素，天然存在于许多常见的食物来源中。白藜芦醇的抗氧化特性特别令人感兴趣，因为氧化剂损伤在多种形式的肾损伤中起着根本作用。为了研究白藜芦醇是否可以阻止肾上皮细胞系 mIMCD-3 细胞的损伤，将细胞暴露于过氧亚硝酸盐供体 5-氨基-3-(4-吗啉基)-1,2,3-恶二唑氯化物（SIN-1）。白藜芦醇产生浓度依赖性抑制由 SIN-1 诱导的细胞毒性。为了研究保护机制，将白藜芦醇与真正的过氧亚硝酸盐孵育，发现其可以阻断牛血清白蛋白的硝化，EC（50）值为 22.7 microM，而众所周知的 RNS 清除剂 N-乙酰-L-半胱氨酸的 EC（50）值为 439 microM。这些数据表明，白藜芦醇可以通过直接清除过氧亚硝酸盐提供功能保护。为了研究白藜芦醇是否是过氧亚硝酸盐氧化的底物，将白藜芦醇与真正的过氧亚硝酸盐反应。使用带有串联电喷雾质谱的液相色谱检测白藜芦醇硝化产物和二聚体。在用 SIN-1 和白藜芦醇处理的细胞的培养基中也检测到了类似的产物。总的来说，这些数据表明，白藜芦醇至少部分通过直接清除 RNS 过氧亚硝酸盐来提供肾管状细胞的功能保护。白藜芦醇的这种特性可能有助于理解其抗氧化活性。
