Epicatechin attenuates doxorubicin-induced brain toxicity: Critical role of TNF-alpha, iNOS and NF-kappa B

Doxorubicin (DOX) is considered one of the most important chemotherapeutic agents that is used for the treatment of solid tumors. Its long-term use can cause neurodegenerative disorders due to its prolonged activation of microglia. The present study proved that the use of epicatechin prior to DOX treatment significantly attenuated not only the increase in TNF-alpha, iNOS and NF-kappa B expressions but also the increase in TNF-alpha and total nitrite levels in brain tissue when compared with rats treated with DOX-only. Thus, our study revealed that epicatechin can be used for the treatment of neuroinflammation and also for preventing the development of neurodegenerative disease during antineoplastic therapy because of its protective role in attenuation of neurotoxic pro-inflammatory mediators including TNF-alpha, NF-kappa B, and iNOS. (C) 2011 Elsevier Inc. All rights reserved.