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Research Article

Cyp4a14 overexpression induced by hyperoxia in female CBA mice as a possible contributor of increased resistance to oxidative stress

, , , , , , , , , & show all
Pages 181-190 | Received 26 May 2009, Published online: 12 Nov 2009
 

Abstract

The beneficial effects of hyperoxia have been noted in treatment of several diseases and pathological states. However, the excessive production of ROS under hyperoxic conditions can directly damage cellular macromolecules if the imbalance in antioxidant status exists. Cytochrome P450 (Cyp) 4a14 has an important role in the metabolism of lipids and as a source of ROS in oxidative stress. This study investigated the oxidant/antioxidant status as a response to hyperoxia treatment in liver of young CBA/Hr mice of both sexes and whether the observed response is mediated by Cyp4a14 via PPAR isoforms in a sex-dependent manner. The overexpression of Cyp4a14, lack of both LPO and of 4-hydroxynonenal(HNE)-protein adducts revealed by immunohistochemical analysis in hyperoxia-treated females indicates their greater resistance to hyperoxia compared to males, which is parallelled to changes in PPARβ/δ and PPARγ expression. These results suggest the presence of sex-dependent changes in all investigated parameters, which points out sex-related susceptibility towards oxidative stress and hyperoxia treatment of various pathological conditions and diseases.

Acknowledgements

We thank Iva Pešun-Međimorec for her excellent technical assistance. The research is funded by Croatian Ministry of Science, Education and Sports, Grant No. 0982464-1647 within collaborations of the COST B35 Action.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 11 November 2009.

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