Dehydrozingerone protects temozolomide-induced cognitive impairment in normal and C6 glioma rats besides enhancing its a
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ORIGINAL ARTICLE
Dehydrozingerone protects temozolomide‑induced cognitive impairment in normal and C6 glioma rats besides enhancing its anticancer potential Nandini Pathak1 · Sri Pragnya Cheruku1 · Vanishree Rao1 · R. J. A. Vibhavari1 · Suhani Sumalatha2 · Karthik Gourishetti1 · C. Mallikarjuna Rao1 · Nitesh Kumar1 Received: 8 June 2020 / Accepted: 4 September 2020 © The Author(s) 2020
Abstract 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. Keywords C6 glioblastoma · Dehydrozingerone · Cognition · Temozolomide
Introduction Chemotherapy is one of the oldest treatment modalities aimed at reducing the tumor burden and improving progression-free overall survival after surgery or radiation therapy. Unfortunately, it is ill-famed to cause cognitive deficits in 70% of cancer patients, of which about 50% report a significant decline in cognitive processes. This is mainly due to its non-selective actions affecting both cancer cells and normal cells. Chemotherapy mediated neurotoxicity has * Nitesh Kumar [email protected]; [email protected] 1
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
Department of Anatomy, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
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gained much importance in recent years, mainly manifested by impaired attention, executive functions, memory, etc., even after cessation of therapy, consequently compromising the quality of life. This is termed as ‘chemo-fog’ or ‘chemobrain’ (Lucassen 2012). Glioma/glioblast
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