Pomalidomide ameliorates H2O2-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects

Yan Rou Tsai, Cheng Fu Chang, Jing Huei Lai, John Chung Che Wu, Yen Hua Chen, Shuo Jhen Kang, Barry J. Hoffer, David Tweedie, Weiming Luo, Nigel H. Greig, Yung Hsiao Chiang, Kai Yun Chen

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Abstract

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2 O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2 O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 19 2018

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Keywords

  • Ischemia
  • Neurodegeneration
  • Neuroprotection
  • Oxidative stress
  • Pomalidomide
  • Stroke

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