title: Neuroprotective effects of tibolone against oxidative stress induced by ozone exposure.
abstract: BACKGROUND
  Oxidative stress increases brain lipid peroxidation, memory and motor deficits and progressive neurodegeneration. Tibolone, a treatment for menopausal symptoms, decreases lipid peroxidation levels and improves memory and learning.
  
  
  OBJECTIVE
  To study the effect of chronic administration of tibolone on lipid peroxidation, memory and motor deficits in ozone induced oxidative stress.
  
  
  METHODS
  100 male Wistar adult rats were randomly divided into 10 experimental groups: control (C) was exposed to an airstream for 60 days; C + tibolone, airstream exposure plus 1 mg/kg of tibolone for 60 days; groups 3-6 were exposed to ozone for 7, 15, 30, and 60 days, and groups 7-10 received 1 mg/kg of tibolone treatment by oral gavage for 7, 15, 30 and 60 days and were then exposed to ozone. We determined the effect of tibolone on memory and motor activity. Hippocampus was processed to determine the content of 4-hydroxynonenal and nitrotyrosine by Western blot. Four animals were perfused and processed for analysis of neuronal death.
  
  
  RESULTS
  In the hippocampus, administration of 1 mg/kg of tibolone for 30 days prevented increased levels of lipid peroxidation and protein oxidation, whereas after 60 days prevented neuronal death in the CA3 region caused by exposure to ozone. Therefore, tibolone prevents cognitive deficits in short- and long-term memory on the passive avoidance task and prevents a decrease in exploratory behavior and an increase in freezing behavior.
  
  
  CONCLUSIONS
  Our results indicate a possible neuroprotective role of tibolone as a useful treatment to prevent oxidative stress neurodegeneration.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pinto-Almazán
authors.forename: Selva
authors.initials: S
authors.lastname: Rivas-Arancibia
authors.forename: Eunice D
authors.initials: ED
authors.lastname: Farfán-García
authors.forename: Erika
authors.initials: E
authors.lastname: Rodríguez-Martínez
authors.affiliation: IMSS. Instituto Mexicano del Seguro Social. CMN, Siglo XXI, Mexico DF, Mexico.
authors.forename: Christian
authors.initials: C
authors.lastname: Guerra-Araiza
mesh_terms: D000447:Aldehydes / Q000032:analysis; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001522:Behavior, Animal / Q000187:drug effects*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology; D007858:Learning / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009652:Norpregnenes / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D010126:Ozone / Q000633:toxicity*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D000447:Aldehydes; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009652:Norpregnenes; C002744:3-nitrotyrosine; D014443:Tyrosine; D010126:Ozone; C027385:tibolone; C027576:4-hydroxy-2-nonenal