Preventive effect of MitoQ supplementation and endurance training on glioblastoma and its consequences: TLR4/CREB/ NF-κβ /IL-1β pathway and behaviors.

Abstract

Objective: The present study investigated the preventive effect of MitoQ supplementation and endurance training (ET) on the TLR4/CREB/ NF-κβ signaling pathway, antioxidant indices, and behaviors in C6-induced glioblastoma (GBM) in rats.

Methods: 60 male Wistar rats were randomly divided into five groups (n = 12); Sham, Tumor, MitoQ, ET, and MitoQ + ET. Rats in the training groups performed endurance training (5 days per week), and MitoQ at the dose of 250 µM/L daily was administered in drinking water for 8 weeks. At the end of the protocol, all groups except the sham group received 1*10⁶ tumor cells /10 µl culture medium. Two weeks after tumor induction, behavioral tests were performed, and then brain tissue was collected for the histopathology, measurement of antioxidant and inflammatory factors, TLR4, NF-κB proteins, and TLR4, NF-κβ, CREB, IL-1ß, TNF-a, IL-10, Bax, Bcl-2, and Caspase-3 gene expression.

Results: The increased level of TLR4 and NF-κβ protein expression in GBM rats decreased in the treatment groups. Gene expression of TLR4, NF-κβ, CREB, TNF-a, IL-10, and Bcl-2 increased in the tumor groups, and treatment groups decreased TLR4, NF-κB, Bcl-2, and CREB. In addition, social behaviors, balance, and memory were impaired in the tumor group, which combination group could improve these behaviors.

Conclusion: In sum, the preventive effects of MitoQ as a beneficial immune reactive agent and exercise training in rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, inflammatory factors, and down-regulation of the expression of TLR4.