title: Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB.
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.
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Turillazzi
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Neri
authors.affiliation: Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerretani
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Cantatore
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Roma, Italy.|Neuromed, Istituto Mediterraneo Neurologico (IRCCS), Pozzilli, Isernia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Frati
authors.affiliation: Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Moltoni
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Roma, Italy.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Busardò
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Pomara
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Riezzo
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Roma, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fineschi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077603:Nandrolone Decanoate; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D045165:Testosterone Congeners / Q000009:adverse effects*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C493454:Slc18a2 protein, rat; D045165:Testosterone Congeners; D050493:Vesicular Monoamine Transport Proteins; D009277:Nandrolone; D000077603:Nandrolone Decanoate
keywords: apoptosis; nandrolone decanoate; neurotoxicity; oxidative stress
references.citation: Neuroscience. 2006;138(3):793-9
references.pmid: 16310317
references.citation: J Neurochem. 1995 Apr;64(4):1703-7
references.pmid: 7891098
references.citation: Mol Pharmacol. 2007 Sep;72(3):744-52
references.pmid: 17576792
references.citation: Mini Rev Med Chem. 2011 May;11(5):362-73
references.pmid: 21443514
references.citation: Drug Alcohol Depend. 2008 Nov 1;98 (1-2):1-12
references.pmid: 18599224
references.citation: J Comp Neurol. 1990 Apr 1;294(1):76-95
references.pmid: 2324335
references.citation: Brain Res. 2005 May 17;1044(1):67-75
references.pmid: 15862791
references.citation: Biochim Biophys Acta. 2010 Oct-Dec;1799(10-12):775-87
references.pmid: 20493977
references.citation: Science. 2001 Nov 9;294(5545):1346-9
references.pmid: 11701929
references.citation: J Alzheimers Dis. 2014;40(3):563-73
references.pmid: 24496073
references.citation: Curr Neuropharmacol. 2015 Jan;13(1):5-11
references.pmid: 26074739
references.citation: Neurosci Lett. 2004 Feb 12;356(2):131-4
references.pmid: 14746881
references.citation: Nat Med. 2002 Jun;8(6):600-6
references.pmid: 12042811
references.citation: Endocrinology. 2009 Dec;150(12):5539-48
references.pmid: 19837873
references.citation: Am J Physiol Cell Physiol. 2008 Oct;295(4):C849-68
references.pmid: 18684987
references.citation: J Neurosci. 1994 Apr;14(4):2260-71
references.pmid: 8158268
references.citation: Brain Res. 2007 Aug 24;1165:21-9
references.pmid: 17662261
references.citation: Br J Pharmacol. 1999 Mar;126(6):1301-6
references.pmid: 10217522
references.citation: Horm Behav. 2008 May;53(5):741-52
references.pmid: 18067894
references.citation: Neuropharmacology. 2014 Aug;83:79-88
references.pmid: 24721625
references.citation: Neurosci Biobehav Rev. 2003 Aug;27(5):413-36
references.pmid: 14505684
references.citation: Brain Res. 2001 Feb 23;892(2):255-62
references.pmid: 11172772
references.citation: Horm Behav. 2010 Jun;58(1):111-21
references.pmid: 19769977
references.citation: Biol Reprod. 1998 Jan;58(1):79-87
references.pmid: 9472926
references.citation: Free Radic Biol Med. 2010 Nov 15;49(9):1342-53
references.pmid: 20696238
references.citation: Nat Immunol. 2011 Jul 19;12(8):715-23
references.pmid: 21772280
references.citation: Am J Psychiatry. 1988 Apr;145(4):487-90
references.pmid: 3279830
references.citation: Physiol Rev. 2007 Jan;87(1):245-313
references.pmid: 17237347
references.citation: EMBO J. 2000 Dec 1;19(23):6351-60
references.pmid: 11101508
references.citation: JAMA. 1988 Dec 16;260(23):3441-5
references.pmid: 3210283
references.citation: Psychiatr Clin North Am. 1993 Mar;16(1):97-103
references.pmid: 8456050
references.citation: Behav Neurosci. 1996 Dec;110(6):1478-86
references.pmid: 8986348
references.citation: Neuropharmacology. 2009;56 Suppl 1:133-8
references.pmid: 18662707
references.citation: J Pharmacol Exp Ther. 2002 Mar;300(3):1093-100
references.pmid: 11861820
references.citation: Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):472-81
references.pmid: 15706095
references.citation: Front Neuroendocrinol. 2008 May;29(2):169-81
references.pmid: 18093638
references.citation: AAPS J. 2005 Dec 20;7(4):E847-51
references.pmid: 16594636
references.citation: Endocrinology. 2013 Nov;154(11):4281-92
references.pmid: 23959938
references.citation: Nat Immunol. 2006 Sep;7(9):954-61
references.pmid: 16892069
references.citation: J Immunol Methods. 2002 Jul 1;265(1-2):49-72
references.pmid: 12072178
references.citation: Curr Neuropharmacol. 2015 Jan;13(1):146-59
references.pmid: 26074749
references.citation: EMBO J. 2003 Jul 1;22(13):3356-66
references.pmid: 12839997
references.citation: Acta Neuropathol. 2013 May;125(5):711-25
references.pmid: 23494099
references.citation: Neuroscience. 2009 Jun 30;161(2):526-37
references.pmid: 19324077
references.citation: Oncogene. 2003 Dec 8;22(56):8961-82
references.pmid: 14663476
references.citation: Annu Rev Pharmacol Toxicol. 1996;36:333-57
references.pmid: 8725393
references.citation: Cell Death Differ. 2006 May;13(5):697-701
references.pmid: 16528380
references.citation: J Cereb Blood Flow Metab. 2002 Apr;22(4):431-43
references.pmid: 11919514
references.citation: Biochem Biophys Res Commun. 2007 Jun 15;357(4):1028-33
references.pmid: 17451646
references.citation: Endocrinology. 1985 Dec;117(6):2471-7
references.pmid: 4065042
references.citation: Mol Neurodegener. 2013 Oct 12;8:40
references.pmid: 24119288
references.citation: Brain Res Rev. 2009 May;60(2):379-407
references.pmid: 19328213
references.citation: J Mol Neurosci. 2005;27(2):167-74
references.pmid: 16186627
references.citation: Clin Ther. 2001 Sep;23(9):1355-90
references.pmid: 11589254
references.citation: EMBO Rep. 2012 Apr 02;13(4):322-30
references.pmid: 22402666
references.citation: J Neurosci. 1992 May;12(5):1658-67
references.pmid: 1578260
references.citation: Drug Alcohol Depend. 2006 Feb 28;81(3):241-9
references.pmid: 16137840
references.citation: Neurosci Lett. 2013 Jan 15;533:28-33
references.pmid: 23063952
references.citation: PLoS One. 2014 Sep 16;9(9):e102699
references.pmid: 25225984
references.citation: J Neurosci. 2012 Aug 22;32(34):11511-23
references.pmid: 22915098
references.citation: J Appl Toxicol. 2012 Oct;32(10):810-4
references.pmid: 21717486
references.citation: J Neural Transm Park Dis Dement Sect. 1993;6(1):45-52
references.pmid: 8105797
references.citation: Biochem Pharmacol. 2006 Oct 30;72(9):1180-95
references.pmid: 16997282
references.citation: J Chromatogr. 1992 May 8;576(2):221-33
references.pmid: 1400710
references.citation: JAMA. 1993 Sep 8;270(10):1217-21
references.pmid: 8355384
references.citation: Eur J Pharmacol. 2007 Sep 24;571(1):25-8
references.pmid: 17618619
references.citation: Mini Rev Med Chem. 2011 May;11(5):390-8
references.pmid: 21443511
references.citation: Toxicol Appl Pharmacol. 2014 Oct 1;280(1):97-106
references.pmid: 25065671
references.citation: Brain Res Bull. 1994;35(4):379-82
references.pmid: 7850490
references.citation: J Pharmacol Exp Ther. 2009 Mar;328(3):807-12
references.pmid: 19038779
references.citation: Horm Behav. 2013 Jul;64(2):350-6
references.pmid: 23274699
references.citation: Nat Immunol. 2002 Mar;3(3):221-7
references.pmid: 11875461
references.citation: J Neurochem. 2006 Jun;97(6):1634-58
references.pmid: 16805774
references.citation: Neuroscience. 2007 Oct 12;149(1):155-64
references.pmid: 17870249
references.citation: Oncogene. 2006 Oct 30;25(51):6731-48
references.pmid: 17072325
references.citation: J Biol Chem. 2006 Sep 1;281(35):25492-501
references.pmid: 16803879
references.citation: J Pharmacol Exp Ther. 2001 Mar;296(3):762-7
references.pmid: 11181904
references.citation: Nat Rev Mol Cell Biol. 2007 Jan;8(1):49-62
references.pmid: 17183360
references.citation: Nature. 2013 May 9;497(7448):211-6
references.pmid: 23636330
references.citation: J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2 Suppl):107-14
references.pmid: 24813319
references.citation: J Neurosci Res. 2011 Apr;89(4):592-600
references.pmid: 21290409
references.citation: Med Sci Law. 2001 Oct;41(4):309-14
references.pmid: 11693226
references.citation: Science. 1971 Jun 18;172(3989):1257-8
references.pmid: 5576164
references.citation: Cold Spring Harb Perspect Biol. 2010 Oct;2(10):a005579
references.pmid: 20826549
references.citation: Genes Brain Behav. 2009 Mar;8(2):161-73
references.pmid: 19055689
references.citation: Toxicol Lett. 2005 Sep 15;158(3):167-75
references.pmid: 16005168
references.citation: Nat Rev Immunol. 2008 Nov;8(11):837-48
references.pmid: 18927578
references.citation: Arch Pediatr Adolesc Med. 1997 Dec;151(12):1197-206
references.pmid: 9412594
references.citation: J Neurosci. 2014 Jun 11;34(24):8210-8
references.pmid: 24920625
references.citation: J Cereb Blood Flow Metab. 2009 Feb;29(2):244-53
references.pmid: 18941467
references.citation: Cell. 2008 Feb 8;132(3):344-62
references.pmid: 18267068
references.citation: Exp Neurol. 2012 Nov;238(1):12-21
references.pmid: 22771760
references.citation: Mutagenesis. 2001 May;16(3):209-12
references.pmid: 11320145
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references.pmid: 18097445
references.citation: Evid Based Complement Alternat Med. 2012;2012:765316
references.pmid: 22997533