The aim of this study was to determine whether treatment of male CBA/H mice with 17β-estradiol (E2) had protective effect on survival and hepatic oxidative damage of lipids and proteins against hyperoxia. Furthermore, we wanted to explore the effect of E2 treatment on the expression of sex-specific cytochrome P450 isoforms, and their possible involvement in E2-induced resistance to hyperoxia. Lipid peroxidation and protein carbonylation were analysed spectrophotometrically and were used as a measure of lipid and protein oxidative damage. Real-time PCR and western blot analysis were used to measure both gene and protein expression levels of Cyp2E1, Cyp7B1 and Cyp2A4, respectively. We found that treatment of male CBA/H mice with E2 increased survival upon hyperoxia exposure, and provided protection against hepatic lipid and protein oxidative damage. Hyperoxia had feminizing effect on the expression of sex-specific CYPs, which resembled the lifespan-promoting conditions. E2 administration had the opposite effect on the expression pattern of these CYPs in hyperoxic versus normoxic conditions. Results of this research proposed possible male strategy in adaptive response to oxidative stress, which may finally result in their longer lifespan.
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We thank Iva Pešun-Međimorec for her excellent technical assistance, dr.sc. Tatjana Marotti for her invaluable expertise, and dr.sc. Anita Kriško for kindly donating the CYP2A antibody. The research is funded by Croatian Ministry of Science, Education and Sports, Grant No. 0982464-1647.
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Šafranko, Ž.M., Balog, T., Musa, M. et al. The effect of 17β-estradiol on sex-dimorphic cytochrome P450 expression patterns induced by hyperoxia in the liver of male CBA/H mice. Mol Cell Biochem 421, 183–191 (2016). https://doi.org/10.1007/s11010-016-2802-2
- Sex dimorphic