Resveratrol, a dietary polyphenolic phytoalexin, is a functional scavenger of peroxynitrite.
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.
Holthoff
Joseph H
JH
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Woodling
Kellie A
KA
Doerge
Daniel R
DR
Burns
Samuel T
ST
Hinson
Jack A
JA
Mayeux
Philip R
PR
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000166:cytology; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000633:toxicity*; D026361:Reactive Nitrogen Species / Q000633:toxicity; D000077185:Resveratrol; D012710:Serum Albumin, Bovine; D013267:Stilbenes / Q000494:pharmacology*
D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D013267:Stilbenes; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; C002385:linsidomine; D008981:Molsidomine; D000077185:Resveratrol