Sodium valproate enhances doxorubicin-induced cognitive dysfunction in Wistar rats

Thaneshwar Verma, Sanchari Basu Mallik, G. V. Ramalingayya, Pawan G. Nayak, Anoop Kishore, K. Sreedhara R. Pai, Krishnadas Nandakumar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Increasing number of scientific reports have highlighted the role of histone acetylation/deacetylation in neurodegenerative conditions, including chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple sources state that increased activity of histone deacetylases (HDACs) play a detrimental role in chemobrain. In the present study, sodium valproate, a well-known HDAC inhibitor, was explored for its neuroprotective potential against chemobrain development. Methods Doxorubicin (DOX), a chemotherapeutic agent, was used to induce chemobrain in experimental animals while treating with sodium valproate simultaneously. The animals were subjected to novel object recognition test (NORT) in order to assess their cognitive status and further, brain antioxidant levels were estimated. The animal body weights and survival were noted throughout the period of the study. Blood parameters such as red blood cell count, white blood cell count and haemoglobin levels were also measured. Results Our findings are in contradiction to the known neuroprotective properties of valproic acid. We observed that sodium valproate failed to prevent chemobrain development in DOX treated animals. In fact, treatment with sodium valproate dose dependently worsened cognitive status in DOX treated animals including their brain antioxidant status, possibly leading to neuronal damage through free radical induced toxicity. Conclusion The present study highlights the caution that needs to be exercised in projecting HDAC inhibitors as in vivo neuroprotective agents, due to the complexity of existing neurological pathways and the diverse roles of histone deacetylases.

Original languageEnglish
Pages (from-to)736-741
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume96
Early online date16-10-2017
DOIs
Publication statusPublished - 01-12-2017

All Science Journal Classification (ASJC) codes

  • Pharmacology

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