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

• Published in: International immunopharmacology 2025-01, Vol.145, p.113756, Article 113756
• Main Authors: Aminizadeh, Soheil, Moslemizadeh, Amir Hossein, Sheibani, Sara, Sedighi-Khovidak, Zahra, Roholamini, Zahrasadat, Jafarinejad-Farsangi, Saeideh, Kheirandish, Reza, Sheibani, Vahid, Bashiri, Hamideh
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Behavior, Animal - drug effects; Behaviors; Brain Neoplasms - metabolism; Brain Neoplasms - prevention & control; Cell Line, Tumor; Cyclic AMP Response Element-Binding Protein - metabolism; Dietary Supplements; Endurance Training; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - metabolism; Humans; Interleukin-1beta - metabolism; Male; MitoQ supplementation; NF-kappa B - metabolism; NF-κβ; Organophosphorus Compounds - pharmacology; Organophosphorus Compounds - therapeutic use; Physical Conditioning, Animal; Rats; Rats, Wistar; Signal Transduction - drug effects; TLR4; Toll-Like Receptor 4 - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; Ubiquinone - therapeutic use
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113756

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. 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. 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. 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.