Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB

J Cell Mol Med. 2016 Apr;20(4):601-12. doi: 10.1111/jcmm.12748. Epub 2016 Feb 1.


The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells.

Keywords: apoptosis; nandrolone decanoate; neurotoxicity; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Feedback, Physiological
  • Gene Expression Regulation
  • Lipid Peroxidation / drug effects
  • Male
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Nandrolone / adverse effects
  • Nandrolone / analogs & derivatives*
  • Nandrolone Decanoate
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Testosterone Congeners / adverse effects*
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism


  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • DIABLO protein, rat
  • Mitochondrial Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Slc18a2 protein, rat
  • Testosterone Congeners
  • Vesicular Monoamine Transport Proteins
  • Nandrolone
  • Nandrolone Decanoate