title: Enhanced antioxidant effect of caffeic acid phenethyl ester and Trolox in combination against radiation induced-oxidative stress.
abstract: Combinations of antioxidants are believed to be more effective than single antioxidant because when antioxidants are combined they support each other synergistically to create a magnified effect. Discovering the enhancer effects or synergies between bioactive components is valuable for resisting oxidative stress and improving health benefits. The aim of this study was to investigate a possible cooperation of natural antioxidant caffeic acid phenethyl ester (CAPE) with synthetic antioxidant Trolox in the model systems of chemical generation of free radicals, lipid peroxidation of microsomes and radiation-induced oxidative injury in L929 cells. Based on the intermolecular interaction between CAPE and Trolox, the present study shows a synergistic effect of CAPE and Trolox in combination on elimination of three different free radicals and inhibition of lipid peroxidation initiated by three different systems. CAPE and Trolox added simultaneously to the L929 cells exerted an enhanced preventive effect on the oxidative injury induced by radiation through decreasing ROS generation, protecting plasma membrane and increasing the ratios of reduced glutathione/oxidized glutathione and the expression of key antioxidant enzymes mediated by nuclear factor erythroid 2 p45-related factor 2 (Nrf2). Our results showed for the first time that administration of CAPE and Trolox in combination may exert synergistic antioxidant effects, and further indicate that CAPE and Trolox combination functions mainly through scavenging ROS directly, inhibiting lipid peroxidation and promoting redox cycle of GSH mediated by Nrf2-regulated glutathione peroxidase and glutathione reductase expression.
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Li
authors.affiliation: Department of Toxicology, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: cx-hai@fmmu.edu.cn.
authors.forename: Chun-Xu
authors.initials: CX
authors.lastname: Hai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002839:Chromans / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005720:Gamma Rays; D019803:Glutathione Disulfide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010851:Picrates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002109:Caffeic Acids; D002839:Chromans; D016166:Free Radical Scavengers; D010851:Picrates; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C004931:1,1-diphenyl-2-picrylhydrazyl; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D019803:Glutathione Disulfide
keywords: Caffeic acid phenethyl ester; Nrf2; Oxidative stress; Radiation; Trolox