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

Emanuela Turillazzi,Santina Cantatore,Paola Frati,Francesco Paolo Busardò,Irene Riezzo,Laura Moltoni,Daniela Cerretani,Vittorio Fineschi,Margherita Neri,Cristoforo Pomara

doi:10.1111/jcmm.12748

Abstract

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.

Highlights

Anabolic androgenic steroids (AASs) are a group of synthetic compounds obtained by selective chemical manipulations of the 19carbon testosterone molecule that affect the pharmacokinetics as well as the ratio of the anabolic/androgenic effect [1]
As there is growing evidence of the potential role of oxidative stress and apoptosis for AASs-mediated neurotoxicity, the aim of this study was to evaluate the role played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND), one of the most frequently abused AASs
Reactive oxygen species act as second messengers in various biological responses, among which the induction of programmed cell death is of paramount importance in our understanding of many common diseases and degenerative conditions [91]

Summary

Introduction

Anabolic androgenic steroids (AASs) are a group of synthetic compounds obtained by selective chemical manipulations of the 19carbon testosterone molecule that affect the pharmacokinetics as well as the ratio of the anabolic/androgenic effect [1]. Behavioural effects include increased confidence, energy and motivation accompanied by irritability and agitation [12, 13], whereas prolonged use is usually associated with loss of inhibition and impulsive and markedly aggressive behaviour [13] by significantly modifying both serotonergic and noradrenergic neurotransmission [14]. It is not yet fully clarified whether AASs are toxic to neurons and whether their abuse is a risk factor for chronic neurodegenerative disorders, growing evidence supports a neurodegenerative potential for AASs [15, 16]. The neurodegenerative effects of long-term AASs a 2016 The Authors

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