Regulation of Redox Profile and Genomic Instability by Physical Exercise Contributes to Neuroprotection in Mice with Experimental Glioblastoma

Abstract

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training's effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

Keywords: brain tumor; genomic stability; glioblastoma; oxidative stress; physical exercise.

Figure 1

Body mass data from animals subjected to an experimental model of glioblastoma and physical training. (a) Mean body mass before surgery, (b) mean body mass after surgery, (c) mean body mass during and after the training phase. Gut, untrained glioblastoma (n = 15); Gtr, trained glioblastoma (n = 12); Sut, untrained sham (n = 10); Str, trained sham (n = 10). * difference between sham versus GBM group.

Figure 2

Open-field test of animals exposed to an experimental model of glioblastoma. Number of crossings (a), number of elevations (b), latency for exit from the center of the quadrant (c), length of stay in the periphery (d). Gut, untrained glioblastoma (n = 15); Gtr, trained glioblastoma (n = 12); Sut, untrained sham (n = 10); Str, trained sham (n = 10).

Figure 3

Rotarod of animals exposed to an experimental model of glioblastoma (GBM). Comparison of the rotarod between the sham and experimental groups 7 days after GBM induction (a), percentage of changes of the experimental groups in relation to the data of 7 days (b). Gut, untrained glioblastoma (n = 15); Gtr, trained glioblastoma (n = 12); Sut, untrained sham (n = 10); Str, trained sham (n = 10).

Figure 4

Analysis of reactive oxygen species (ROS) production of animals exposed to an experimental model of glioblastoma. Levels of ROS in the right parietal (a), cortex (b), and quadriceps (c). Gut, untrained glioblastoma (n = 15); Gtr, trained Glioblastoma (n = 12); Sut, untrained sham (n = 10); Str, trained sham (n = 10).

Figure 5

Oxidative damage of animals exposed to an experimental model of glioblastoma. Levels of lipoperoxidation in the right parietal (a) and carbonylation of proteins in the right parietal (b), cortex (c), and quadriceps (d). Gut, untrained glioblastoma (n = 15); Gtr, trained glioblastoma (n = 12); Sut, untrained sham (n = 10); Str, trained sham (n = 10).

Figure 6

DNA damage parameters in the blood (a) and liver (b) of animals exposed to an experimental model of glioblastoma. Sut, untrained sham (n = 10); Gut, untrained glioblastoma (n = 15); Str, trained sham (n = 10); Gtr, trained glioblastoma (n = 12).