RT Journal Article T1 Impact of Exposure Duration to High-Altitude Hypoxia on Oxidative Homeostasis in Rat Brain Regions A1 Lira-Mejía, Boris A1 Calderon-Romero, Roger A1 Ordaya-Fierro, Jorge A1 Medina, Cristian A1 Rodríguez, José-Luis A1 Romero Martínez, Manuel Alejandro A1 Dávila, Roberto A1 Ramos-Gonzalez, Mariella AB Hypoxia at altitudes above 3000 m poses a significant threat to organ health and physiological homeostasis, particularly in metabolically active tissues such as the brain. Many of the cellular alterations induced by hypoxia are associated with the excessive generation of reactive oxygen species (ROS) and the resulting oxidative stress. In this study, we investigated the effects of exposure duration and altitude levels on oxidative homeostasis in the rat hypothalamus, cortex, hippocampus, and striatum. We assessed ROS production, malondialdehyde (MDA) levels, the antioxidant activities of superoxide dismutase (SOD), and catalase, as well as molecular biomarkers of oxidative stress, cell death, and inflammation. Our findings demonstrated that ROS, MDA and SOD levels increased across all brain regions, particularly in response to higher altitude exposure. Conversely, catalase activity decreased under the same conditions. At the molecular level, we observed overexpression of key biomarkers related to oxidative stress, cell death, and inflammation, especially at extreme altitudes. Furthermore, these effects were most pronounced in the hippocampus, cortex, and striatum. In conclusion, our data indicate that hypoxic exposure at higher altitudes significantly contributes to the oxidative disruption of brain homeostasis in rats PB MDPI SN 1661-6596 YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/124749 UL https://hdl.handle.net/20.500.14352/124749 LA eng NO Lira-Mejía, B., Calderon-Romero, R., Ordaya-Fierro, J., Medina, C., Rodríguez, J. L., Romero, A., Dávila, R., & Ramos-Gonzalez, M. (2025). Impact of Exposure Duration to High-Altitude Hypoxia on Oxidative Homeostasis in Rat Brain Regions. International journal of molecular sciences, 26(17), 8714. https://doi.org/10.3390/ijms26178714 NO Author Contributions: Conceptualization, B.L.-M., J.-L.R. and M.R.-G.; Data curation, B.L.-M. and J.- L.R.; Formal analysis, B.L.-M., A.R. and R.D.; Funding acquisition, R.C.-R. and B.L.-M.; Investigation, B.L.-M., R.C.-R., C.M., J.O.-F. and R.D.; Methodology, B.L.-M., J.-L.R., A.R. and M.R.-G.; Project administration, B.L.-M. and M.R.-G.; Resources, B.L.-M. and R.C.-R.; Software, A.R. and J.-L.R.; Validation, R.C.-R., J.O.-F., C.M. and M.R.-G.; Visualization, B.L.-M., J.-L.R. and A.R.; Writing— original draft, A.R., B.L.-M. and J.-L.R.; Writing—review and editing, A.R., B.L.-M. and J.-L.R. All authors have read and agreed to the published version of the manuscript NO Universidad Nacional Mayor de San Marcos ( Perú ) NO PROCIENCIA-CONCYTEC ( Perú ) DS Docta Complutense RD 19 mar 2026