Neuropharmacology · 2026
Therapeutic potential and toxicological trade-offs of nanoparticle-enhanced valproic acid in glioblastoma: Behavioral and oxidative insights.
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Khodayari Negin, Sedghy Farnaz, Ranjbar Mehdi, Pashazadeh Azari Pouya, Houshmand Fatemeh, Shahrokhi Raeini Azadeh, Mahmoodi Merat, Bashiri Hamideh, Kheirandish Reza
Аннотация
BACKGROUND: Glioblastoma (GBM) is a highly aggressive brain tumor with a poor prognosis. In the current research, the therapeutic and behavioral efficacy of valproic acid (VPA) and its nanoparticles (Nano VPA) with or without temozolomide (TMZ) was investigated in the C6 glioblastoma rat model.
METHODS: We divided eighty-four adult male Wistar rats into seven groups (n = 12/group): sham, tumor, TMZ, VPA, nano VPA, VPA + TMZ, and nano VPA + TMZ. To induce tumors, C6 cells were injected into the brains of the rats. On days 12 to 15, behavioral performance was assessed using the social interaction test, elevated plus maze, open field, rotarod, and passive avoidance. On day 18, tumor size, edema, and histopathology were examined. Oxidative stress parameters in brain tissue and serum were measured by ELISA.
RESULTS: VPA and Nano VPA significantly inhibited tumor growth, either alone or with TMZ. All treatments except Nano VPA + TMZ improved survival compared with tumor controls. Treated groups showed enhanced anxiety regulation, sociability, learning, and memory. Motor coordination improved following VPA or Nano VPA therapy. Tumor induction reduced serum SOD, CAT, and TAC levels; treatments raised serum TAC and lowered brain MDA, but further reduced serum SOD.
CONCLUSION: Our results suggest that oxidative stress modulation may contribute to the neurobehavioral and antitumor effects of both VPA and nano-VPA. While nano-VPA showed greater tumor reduction, conventional VPA was more effective in improving survival. Combining VPA with TMZ may enhance outcomes, and support further study of Nano VPA as an adjuvant therapy for GBM.
METHODS: We divided eighty-four adult male Wistar rats into seven groups (n = 12/group): sham, tumor, TMZ, VPA, nano VPA, VPA + TMZ, and nano VPA + TMZ. To induce tumors, C6 cells were injected into the brains of the rats. On days 12 to 15, behavioral performance was assessed using the social interaction test, elevated plus maze, open field, rotarod, and passive avoidance. On day 18, tumor size, edema, and histopathology were examined. Oxidative stress parameters in brain tissue and serum were measured by ELISA.
RESULTS: VPA and Nano VPA significantly inhibited tumor growth, either alone or with TMZ. All treatments except Nano VPA + TMZ improved survival compared with tumor controls. Treated groups showed enhanced anxiety regulation, sociability, learning, and memory. Motor coordination improved following VPA or Nano VPA therapy. Tumor induction reduced serum SOD, CAT, and TAC levels; treatments raised serum TAC and lowered brain MDA, but further reduced serum SOD.
CONCLUSION: Our results suggest that oxidative stress modulation may contribute to the neurobehavioral and antitumor effects of both VPA and nano-VPA. While nano-VPA showed greater tumor reduction, conventional VPA was more effective in improving survival. Combining VPA with TMZ may enhance outcomes, and support further study of Nano VPA as an adjuvant therapy for GBM.