Gender Differences in the Antioxidant Response to Oxidative Stress in Experimental Brain Tumors

Background: Brain tumorigenesis is related to oxidative stress and a decreased response of antioxidant defense systems. As it is well known that gender differences exist in the incidence and survival rates of brain tumors, it is important to recognize and understand the ways in which their biology can differ. Objective: To analyze gender differences in redox status in animals with chemically-induced brain tumors. Methods: Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems are assayed in animals with brain tumors induced by transplacental N-ethyl-N-nitrosourea (ENU) administration. Both tissue and plasma were analyzed to know if key changes in redox imbalance involved in brain tumor development were reflected systemically and could be used as biomarkers of the disease. Results: Several oxidative stress parameters were modified in tumor tissue of male and female animals, changes that were not reflected at plasma level. Regarding antioxidant defense system, only glutathione (GSH) levels were decreased in both brain tumor tissue and plasma. Superoxide dismutase (SOD) and catalase (CAT) activities were decreased in brain tumor tissue of male and female animals, but plasma levels were only altered in male animals. However, different protein and mRNA expression patterns were found for both enzymes. On the contrary, glutathione peroxidase (GPx) activity showed increased levels in brain tumor tissue without gender differences, being protein and gene expression also increased in both males and female animals. However, these changes in GPx were not reflected at plasma level. Conclusion: We conclude that brain tumorigenesis was related to oxidative stress and changes in brain enzyme and non-enzyme antioxidant defense systems with gender differences, whereas plasma did not reflect the main redox changes that occur at the brain level.