Background: This study assessed the effects of single or combined administration of temozolomide (TMZ) and interferon-gamma (IFN-ᵞ) on anxiety-like behaviors, balance disorders, learning and memory, TNF-α, IL-10, some oxidant and antioxidants factors with investigating the toll-like receptor-4 (TLR4) and p-CREB signaling pathway in C6-induced glioblastoma of rats.
Methods: 40 male Sprague-Dawley rats bearing intra-caudate nucleus (CN) culture medium or C6 inoculation were randomly divided into five groups as follows: Sham, Tumor, TMZ, IFN-ᵞ and a TMZ + IFN-ᵞ combination. The open-field test (OFT), elevated plus maze (EPM), rotarod, and passive avoidance test (PAT) were done on days 14-17. On day 17 after tumor implantation, brain tissues were extracted for histopathological evaluation. TNF-α, IL-10, SOD, GPX, TAC, MDA, the protein level of TLR4 and p-CREB was measured.
Results: Combination therapy inhibited the growth of the tumor. Treatment groups alleviated tumor-induced anxiety-like behaviors and improved imbalance and memory impairment. SOD, GPX, and TAC decreased in the tumor group. The combination group augmented GPX and TAC. MDA decreased in treatment groups. TMZ, IFN-ᵞ reduced tumor-increased TNF-α and IL-10 level. The combination group declined TNF-α level in serum and IL-10 level in serum and brain. Glioblastoma induced significant upregulation of TLR4 and p-CREB in the brain which inhibited by IFN-ᵞ and TMZ+ IFN-ᵞ.
Conclusion: The beneficial effects of TMZ, IFN-ᵞ, and TMZ+ IFN-ᵞ on neurocognitive functioning of rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, reduced cytokines, and the downregulation of expression of TLR4 and p-CREB. Combination treatment appears to be more effective than single treatment.
Keywords: Cognitive behaviors; Glioblastoma; Inflammatory factors; Interferon gamma; Oxidative stress; Temozolomide.
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