Considering the
cognitive impairment induced by
temozolomide (TMZ) in
glioblastoma survivors, the present study was aimed to evaluate the protective effect of
dehydrozingerone (DHZ) against TMZ-induced
cognitive impairment (
chemobrain) and C6 cell line-induced
glioma in male Wistar rats. In both
chemobrain and
glioma models, TMZ was administered at a dose of 18 mg/kg i.v every 5th day and DHZ at a dose of 100 mg/kg p.o. daily. Additionally,
glioma was induced by intracerebral injection of 5 × 104 C6 rat
glioma cells in the cortex in the
glioma model. Upon disease induction and treatment with TMZ + DHZ, spatial memory was assessed by the Morris water maze (MWM) test and episodic memory by the novel object recognition test (NORT). The induction of
glioma was confirmed by histology of the cortex. Hippocampus and frontal cortex were subjected to
antioxidant evaluation. Significant loss of spatial and episodic memory was observed with TMZ treatment which was significantly restored by DHZ. DHZ showed significant improvement in oxidative stress markers reversed the histopathological features in the cortex. TMZ-induced elevation of the
glutathione level was also reversed by DHZ, indicating the role of DHZ in the reversal of TMZ resistance. In the
glioma model, the improvement in cognition by DHZ correlated with the decrease in
tumor volume. Altogether, the study results reveal the role of TMZ in worsening the memory and DHZ in reversing it, besides, improving its anticancer potential.