Vericiguat as an adjunct to temozolomide therapy improves behavioral and tumor outcomes in experimental glioblastoma.

Glioblastoma (GBM) is an aggressive brain tumor with limited effective therapies. The standard agent, Temozolomide (TMZ) though beneficial, often induces neurocognitive side effects that compromise quality of life. This study examined whether combining Vericiguat; a soluble guanylate cyclase stimulator, with standard or reduced TMZ doses could enhance antitumor efficacy and behavioral outcomes while reducing adverse effects in a rat model of GBM. 80 male Wistar rats received intracerebral injections of C6 glioma cells and were assigned to eight groups: Sham, Tumor, Vehicle, TMZ 3.75 mg/kg, TMZ 7.5 mg/kg, Vericiguat 0.5 mg/kg, and their combinations. Behavioral assessments (open field, elevated plus maze, rotarod, passive avoidance, and social interaction) were performed on days 20-24. On day 25, brain tissues were analyzed histologically and immunohistochemically (Ki-67). Survival was monitored for three months. Combination therapy significantly improved anxiety-like behavior, motor coordination, learning, memory, and social interaction compared with untreated tumor-bearing rats. Co treatment also extended survival, reduced tumor proliferation (lower Ki-67 expression), and preserved brain tissue structure. Vericiguat combined with low-dose TMZ produced synergistic effects on tumor suppression and neurocognitive recovery in GBM rats. These findings suggest that Vericiguat may enhance TMZ efficacy, enabling dose reduction and minimizing TMZ induced neurotoxicity while maintaining therapeutic effectiveness.