Glutathione Peroxidase gpx1 to gpx8 Genes Expression in Experimental Brain Tumors Reveals Gender-Dependent Patterns

Extensive research efforts in the field of brain tumor studies have led to the reclassification of tumors by the World Health Organization (WHO) and the identification of various molecular subtypes, aimed at enhancing diagnosis and treatment strategies. However, the quest for biomarkers that can provide a deeper understanding of tumor development mechanisms, particularly in the case of gliomas, remains imperative due to their persistently incurable nature. Oxidative stress has been widely recognized as a key mechanism contributing to the formation and progression of malignant tumors, with imbalances in antioxidant defense systems being one of the underlying causes for the excess production of reactive oxygen species (ROS) implicated in tumor initiation. In this study, we investigated the gene expression patterns of the eight known isoforms of glutathione peroxidase (GPx) in brain tissue obtained from male and female control rats, as well as rats with transplacental ethyl nitrosourea (ENU)-induced brain tumors. Employing the delta-delta Ct method for RT-PCR, we observed minimal expression levels of gpx2, gpx5, gpx6, and gpx7 in the brain tissue from the healthy control animals, while gpx3 and gpx8 exhibited moderate expression levels. Notably, gpx1 and gpx4 displayed the highest expression levels. Gender differences were not observed in the expression profiles of these isoforms in the control animals. Conversely, the tumor tissue exhibited elevated relative expression levels in all isoforms, except for gpx4, which remained unchanged, and gpx5, which exhibited alterations solely in female animals. Moreover, except for gpx1, which displayed no gender differences, the relative expression values of gpx2, gpx3, gpx6, gpx7, and gpx8 were significantly higher in the male animals compared to their female counterparts. Hence, the analysis of glutathione peroxidase isoforms may serve as a valuable approach for discerning the behavior of brain tumors in clinical settings.