title: In vivo protective effect of betulinic acid on dexamethasone induced thymocyte apoptosis by reducing oxidative stress.
abstract: BACKGROUND
  Dexamethasone (Dex), a synthetic glucocorticoid, is strictly controlled for use due to its serious side effects, including immune suppression. Betulinic acid (BA), an antioxidant prepared from the white birch, exhibits immunomodulation properties. To assess the implications and investigate the mechanisms of BA-elicited immunomodulation, we hypothesized that Dex induced thymocyte apoptosis via oxidative stress could be lessened by BA.
  
  
  METHODS
  Mice were given oral doses of BA (0.25, 0.5, and 1.0mg/kg) daily for 14 days, and induced oxidative stress by giving a single dose of Dex intraperitoneal at the dosage of 25mg/kg body weight 8h after the last administration of BA.
  
  
  RESULTS
  Dex administration alone significantly decreased antioxidant enzyme activities, while significantly increased reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial dysfunctions, caspase-3 activation and cellular apoptosis. However, pretreatment with BA dose-dependently mitigated Dex-induced oxidative damage after 14 days of feeding. In addition to ROS scavenging activity in Dex-induced thymocyte, BA administration decreased lipid peroxidation, up-regulated antioxidant enzymes, restored mitochondrial function, increased Bcl-2 expression but reduced Bax expression, inhibited caspase-3 activation, and improved cell survival.
  
  
  CONCLUSIONS
  These findings reveal a protective capability of BA against Dex-induced cell death by reducing oxidative stress via mitochondrial mediated signal pathway which could be the potential mechanism underlying BA-elicited immunomodulation.
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China. Electronic address: yijine@gmail.com.
authors.forename: Jine
authors.initials: J
authors.lastname: Yi
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Ruocen
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Agricultural, Food and Nutritional Science, 4-10 Ag/For Center, University of Alberta, Edmonton, Canada.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China.
authors.forename: Siting
authors.initials: S
authors.lastname: Xiang
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China. Electronic address: ztandao@gmail.com.
authors.forename: Zhuliang
authors.initials: Z
authors.lastname: Tan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D053978:Pentacyclic Triterpenes; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D060168:Thymocytes / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D053978:Pentacyclic Triterpenes; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014315:Triterpenes; D003907:Dexamethasone; D000094062:Betulinic Acid
keywords: Apoptosis; Betulinic acid; Dexamethasone; Oxidative stress; Thymocyte