title: BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS-Treated Rats.
abstract: Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin-A receptor antagonist, influences the level of TNF-α, IL-6, SOD-1, HO-1, Nrf2 mRNA, and NF-κB subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (n = 6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later. Injection of LPS led to significant increase in levels of RelA/p65 mRNA, TNF-α, and IL-6, while content of SOD-1, HO-1, and Nrf2 mRNA was unchanged. Administration of BQ123 prior to LPS challenge resulted in a significant reduction in RelA/p65 mRNA, TNF-α, and IL-6 levels, as well as markedly elevated concentrations of SOD-1, HO-1, and Nrf2 mRNA. BQ123 appears to enhance antioxidant defense and prevent production of TNF-α and IL-6 in skeletal muscle of LPS-treated rat. In conclusion, endothelin-A receptor antagonism exerts significant impact on the skeletal muscle favouring anti-inflammatory effects and protection against oxidative stress.
authors.affiliation: Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
authors.forename: Agata
authors.identifier: 0000-0001-9219-118X
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: Laboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jeleń
authors.affiliation: Laboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Żebrowska
authors.affiliation: Laboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Balcerczak
authors.affiliation: Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gorąca
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016207:Cytokines; D065130:Endothelin A Receptor Antagonists / Q000737:chemistry; D065128:Endothelin Receptor Antagonists / Q000737:chemistry; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D010456:Peptides, Cyclic / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D016207:Cytokines; D065130:Endothelin A Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010456:Peptides, Cyclic; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C000606292:Sod1 protein, rat; D000072105:Superoxide Dismutase-1; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
references.citation: Part Fibre Toxicol. 2013;10:11
references.pmid: 23557437
references.citation: Ann Surg. 1991 Mar;213(3):261-4
references.pmid: 1998407
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1159-68
references.pmid: 17584954
references.citation: J Immunol. 2003 Mar 15;170(6):2993-3001
references.pmid: 12626552
references.citation: Biochem Pharmacol. 2008 Dec 1;76(11):1485-9
references.pmid: 18694732
references.citation: Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):95-108
references.pmid: 17200683
references.citation: Basic Res Cardiol. 2000 Apr;95(2):98-105
references.pmid: 10826501
references.citation: Circ Shock. 1991 Apr;33(4):222-7
references.pmid: 2065442
references.citation: Physiol Res. 2008;57(3):373-8
references.pmid: 17465691
references.citation: Inflammation. 2014 Jun;37(3):712-22
references.pmid: 24337631
references.citation: Biochem Biophys Res Commun. 1992 Oct 15;188(1):453-62
references.pmid: 1384489
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L476-84
references.pmid: 12114211
references.citation: J Intensive Care Med. 2007 Jul-Aug;22(4):232-9
references.pmid: 17722367
references.citation: J Physiol. 2010 Apr 15;588(Pt 8):1333-47
references.pmid: 20176631
references.citation: J Physiol. 2007 Jul 1;582(Pt 1):407-19
references.pmid: 17317755
references.citation: Ann Thorac Surg. 2008 Nov;86(5):1576-83
references.pmid: 19049753
references.citation: Gen Physiol Biophys. 2006 Jun;25(2):195-206
references.pmid: 16917132
references.citation: Hypertension. 2003 Oct;42(4):811-7
references.pmid: 12913063
references.citation: Biochim Biophys Acta. 2012 Jun;1822(6):1038-50
references.pmid: 22366763
references.citation: Phytother Res. 2012 Dec;26(12):1904-12
references.pmid: 22431150
references.citation: PLoS One. 2014;9(8):e104924
references.pmid: 25115759
references.citation: Braz J Med Biol Res. 2001 Mar;34(3):301-14
references.pmid: 11262580
references.citation: Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):753-61
references.pmid: 11254535
references.citation: PLoS One. 2011;6(8):e23660
references.pmid: 21858193
references.citation: PLoS One. 2013;8(9):e73457
references.pmid: 24039949
references.citation: Oxid Med Cell Longev. 2015;2015:843721
references.pmid: 26161243
references.citation: Curr Drug Targets. 2010 Dec;11(12):1504-16
references.pmid: 20704550
references.citation: Acta Anaesthesiol Taiwan. 2012 Dec;50(4):159-66
references.pmid: 23385038
references.citation: Pharmacol Rep. 2012;64(6):1434-41
references.pmid: 23406754
references.citation: J Lab Clin Med. 2000 Apr;135(4):324-31
references.pmid: 10779048
references.citation: Curr Probl Pediatr Adolesc Health Care. 2013 Nov-Dec;43(10):260-3
references.pmid: 24295606
references.citation: Toxicology. 2006 Feb 15;219(1-3):142-9
references.pmid: 16406210
references.citation: J Formos Med Assoc. 1996 Mar;95(3):236-40
references.pmid: 8857257
references.citation: Acta Pharmacol Sin. 2003 Jan;24(1):37-44
references.pmid: 12511227
references.citation: Toxicol Appl Pharmacol. 2010 Apr 1;244(1):84-97
references.pmid: 19716833
references.citation: J Agric Food Chem. 2012 Aug 22;60(33):8171-82
references.pmid: 22838648
references.citation: Acta Pharmacol Sin. 2014 Oct;35(10):1274-84
references.pmid: 25152028
references.citation: PLoS One. 2014;9(3):e92048
references.pmid: 24651840
references.citation: Circulation. 2005 Apr 12;111(14):1763-70
references.pmid: 15809365
references.citation: Transl Res. 2008 Feb;151(2):68-78
references.pmid: 18201674
references.citation: Arch Immunol Ther Exp (Warsz). 2015 Feb;63(1):41-52
references.pmid: 25288367
references.citation: J Clin Endocrinol Metab. 2004 Nov;89(11):5627-33
references.pmid: 15531521
references.citation: Evid Based Complement Alternat Med. 2013;2013:590363
references.pmid: 23573137
references.citation: Eur Respir J. 2010 Apr;35(4):904-12
references.pmid: 19897563
references.citation: J Surg Res. 2008 Sep;149(1):138-47
references.pmid: 18639249
references.citation: Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):982-9
references.pmid: 10712352
references.citation: PLoS One. 2013;8(7):e69452
references.pmid: 23894482
references.citation: Med Sci Monit. 2002 Jan;8(1):BR1-7
references.pmid: 11796957
references.citation: Nutrition. 2014 May;30(5):602-11
references.pmid: 24698353
references.citation: Physiol Rep. 2015 Apr;3(4):null
references.pmid: 25911453
references.citation: Pulm Circ. 2014 Jun;4(2):300-10
references.pmid: 25006449
references.citation: Int J Mol Med. 2014 Jul;34(1):74-82
references.pmid: 24756152
references.citation: Brain Res. 2001 Sep 28;914(1-2):15-22
references.pmid: 11578593
references.citation: Biomed Pharmacother. 2010 Nov;64(9):639-46
references.pmid: 20888175
references.citation: Free Radic Biol Med. 2010 May 1;48(9):1252-62
references.pmid: 20156551
references.citation: Int J Sports Med. 1997 Apr;18(3):157-60
references.pmid: 9187967
references.citation: J Am Soc Nephrol. 1999 Dec;10(12):2540-50
references.pmid: 10589693
references.citation: Cell Res. 2011 Jan;21(1):103-15
references.pmid: 21187859
references.citation: Muscle Nerve. 2005 Aug;32(2):140-63
references.pmid: 15825186
references.citation: PLoS One. 2014;9(12):e115854
references.pmid: 25541965
references.citation: Oxid Med Cell Longev. 2012;2012:324256
references.pmid: 22811764
references.citation: PLoS One. 2013;8(10):e76293
references.pmid: 24098466
references.citation: Biochem Biophys Res Commun. 2000 Mar 24;269(3):713-7
references.pmid: 10720482
references.citation: Chem Biol Interact. 1994 Jun;91(2-3):91-100
references.pmid: 8194138
references.citation: J Alzheimers Dis. 2011;23(3):491-503
references.pmid: 21116051
references.citation: Biochem Pharmacol. 2003 Aug 15;66(4):589-94
references.pmid: 12906923
references.citation: Beilstein J Nanotechnol. 2014 Aug 26;5:1357-70
references.pmid: 25247119
references.citation: Hypertension. 2003 Oct;42(4):806-10
references.pmid: 12874096
references.citation: J Ethnopharmacol. 2015 Mar 13;162:168-75
references.pmid: 25571843
references.citation: Neurochem Res. 2012 Oct;37(10):2108-16
references.pmid: 22740163
references.citation: Mediators Inflamm. 2015;2015:380218
references.pmid: 25969626
references.citation: J Appl Physiol (1985). 2015 Apr 1;118(7):818-29
references.pmid: 25549765