title: Plasma metabolite profiles following trauma-hemorrhage: effect of posttreatment with resveratrol.
abstract: Resveratrol (RSV) has been shown to inhibit the inflammatory reaction and ameliorate the organ damage resulting from trauma-hemorrhage (TH). However, the effects of RSV on the metabolomic profiles under these conditions remain unclear. The aim of this study was to determine the metabolomic profiles of plasma in TH rats and to evaluate the therapeutic effects of RSV using high-performance liquid chromatography-mass spectrometry. Thirty male Sprague-Dawley rats were divided into sham operation (n = 10), sham-operation plus RSV treatment (n = 10), TH (n = 10), and TH plus RSV treatment (n = 10) groups. Plasma samples were obtained at 24 h after surgery. Electrospray ionization-tandem mass spectrometry was used to characterize the plasma metabolomes. The systemic analyses of plasma metabolomes and their targets were determined using a number of computational approaches, including principal component analysis, partial least squares discriminant analysis, and heat map analysis. Using these methods, the effects of RSV on the metabolomic profiles in animals that underwent trauma-hemorrhagic injury were determined. These approaches allowed a clear discrimination of the pathophysiological characteristics among the groups. The results demonstrate RSV treatment significantly reduced the metabolic derangements caused by TH. Compared with the sham-operated rats, the plasma levels of carnitine in the TH rats were relatively lower, but the levels of acetylcarnitine and butyrylcarnitine were higher, suggesting that RSV ameliorated the deranged carnitine metabolism in TH rats. There was a statistically significant increase in carnitine. In addition, RSV treatment reduced ketoacidosis and protein degradation, as evidenced by the attenuation of the elevated plasma branched-chain amino acid levels in the TH rats. Our study showed that the alterations of the metabolomic profiles in the rats subjected to trauma-hemorrhagic shock were attenuated by RSV treatment. In view of the metabolomic evidence, we conclude that RSV exerts beneficial effects in trauma-hemorrhagic shock injury and that these effects are partially mediated by improving energy metabolism and reducing protein degradation.
authors.affiliation: *Department of Physiology, †Department of Anesthesiology, Chang Gung Memorial Hospital, ‡Graduate Institute of Clinical Medical Sciences, §College of Medicine, Chang Gung University; and ║Department of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.
authors.forename: Yu-Ren
authors.initials: YR
authors.lastname: Wang
authors.forename: Yung-Fong
authors.initials: YF
authors.lastname: Tsai
authors.forename: Ying-Tung
authors.initials: YT
authors.lastname: Lau
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
mesh_terms: D000818:Animals; D002331:Carnitine / Q000097:blood; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics / Q000379:methods; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013267:Stilbenes / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications*
chemical_list: D013267:Stilbenes; D014665:Vasodilator Agents; D000077185:Resveratrol; D002331:Carnitine