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.