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Neuroprotective effects of tibolone against oxidative stress induced by ozone exposure.

Abstract：

INTRODUCTION: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. AIM:To study the effect of chronic administration of tibolone on lipid peroxidation, memory and motor deficits in ozone induced oxidative stress. MATERIALS AND 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. CONCLUSION:Our results indicate a possible neuroprotective role of tibolone as a useful treatment to prevent oxidative stress neurodegeneration. TITLE:Efecto neuroprotector de la tibolona contra el estres oxidativo inducido por la exposicion a ozono. :Introduccion. El estres oxidativo aumenta la lipoperoxidacion, produce deficits de memoria y de actividad motora asi como una neurodegeneracion progresiva en el sistema nervioso central. La tibolona es un tratamiento para los sintomas de la menopausia que disminuye los niveles de peroxidacion de lipidos y mejora la memoria y el aprendizaje. Objetivo. Estudiar el efecto de la tibolona sobre la peroxidacion de lipidos, los deficits de memoria y motor en el modelo de estres oxidativo inducido por la exposicion cronica al ozono. Materiales y metodos. Se dividieron aleatoriamente 100 ratas adultas Wistar en 10 grupos: control (C), que recibio aire durante 60 dias; (C + tibolona), aire mas 1 mg/kg de tibolona durante 60 dias; los grupos 3-6, ozono durante 7, 15, 30, y 60 dias; y los grupos 7-10, 1 mg/kg de tibolona durante 7, 15, 30 y 60 dias previo a la exposicion al ozono. Se realizaron pruebas de memoria y motoras y se determino el contenido del 4-hidroxinonenal y de la nitrotirosina por Western blot, asi como la muerte neuronal en el hipocampo. Resultados. La administracion de tibolona disminuyo el contenido de lipidos peroxidados, la oxidacion de proteinas y la muerte neuronal en el hipocampo; mejoro la memoria y previno las alteraciones motoras en los animales expuestos a ozono. Conclusion. Nuestros resultados indican un posible papel neuroprotector de la tibolona como un tratamiento util para prevenir la neurodegeneracion inducida por el estres oxidativo.

journal_name

Rev Neurol

journal_title

Revista de neurologia

authors

Pinto-Almazán R,Rivas-Arancibia S,Farfán-García ED,Rodríguez-Martínez E,Guerra-Araiza C

subject

Has Abstract

pub_date

2014-05-16 00:00:00

pages

441-8

issue

eissn

0210-0010

issn

1576-6578

pii

rn2013357

journal_volume

pub_type

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Neuroprotective effects of tibolone against oxidative stress induced by ozone exposure.