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Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice

Ana Šarić, Sandra Sobočanec, Željka Mačak Šafranko, Marijana Popović Hadžija, Robert Bagarić, Vladimir Farkaš, Alfred Švarc, Tatjana Marotti, Tihomir Balog

Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia

Med Sci Monit Basic Res 2015; 21:191-199

DOI: 10.12659/MSMBR.895356

Available online: 2015-09-16

Published: 2015-09-16


BACKGROUND: We have explored sex differences in ability to maintain redox balance during acute oxidative stress in brains of mice. We aimed to determine if there were differences in oxidative/antioxidative status upon hyperoxia in brains of reproductively senescent CBA/H mice in order to elucidate some of the possible mechanisms of lifespan regulation.
MATERIAL AND METHODS: The brains of 12-month-old male and female CBA/H mice (n=9 per sex and treatment) subjected to 18-h hyperoxia were evaluated for lipid peroxidation (LPO), antioxidative enzyme expression and activity - superoxide dismutase 1 and 2 (Sod-1, Sod-2), catalase (Cat), glutathione peroxidase 1 (Gpx-1), heme-oxygenase 1 (Ho-1), nad NF-E2-related factor 2 (Nrf2), and for 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake.
RESULTS: No increase in LPO was observed after hyperoxia, regardless of sex. Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023). Also, in females hyperoxia upregulated Sod-1 (p=0.046), and Ho-1 (p=0.014) genes. SOD1 protein was upregulated in both sexes after hyperoxia (p=0.009 for males and p=0.011 for females). SOD2 protein was upregulated only in females (p=0.008) while CAT (p=0.026) and HO-1 (p=0.042) proteins were increased after hyperoxia only in males. Uptake of 18FDG was decreased after hyperoxia in the back brain of females.
CONCLUSIONS: We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males. We propose this model of hyperoxia as a useful tool to assess sex differences in adaptive response to acute stress conditions, which may be partially responsible for observed sex differences in longevity of CBA/H mice.

Keywords: Brain - metabolism, Anoxia - metabolism, Animals, Catalase - metabolism, Disease Models, Animal, disease resistance, Glutathione Peroxidase - metabolism, Lipid Peroxidation, Mice, Mice, Inbred CBA, Neuroimaging, Oxidation-Reduction, Oxidative Stress - physiology, Sex Factors, Superoxide Dismutase - metabolism