title: Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects.
abstract: BACKGROUND
  Heme oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e.g., postoperative ileus, gastroparesis, acute pancreatitis, and colitis). However, the only drugs (i.e., hemin and heme arginate) which pharmacologically upregulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin, and simvastatin alone, and with α-lipoic acid, on HO-1 protein concentration and activity in humans.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled study compared the effects of three oral regimens administered for 7 days, i.e., placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R- α-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i.e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2, and 7.
  
  
  RESULTS
  Baseline HO-1 protein concentrations and activity were similar among the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2.
  
  
  CONCLUSIONS
  At therapeutic doses, aspirin, simvastatin, and α-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans.
authors.affiliation: Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
authors.forename: Adil E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: Kyoung Moo
authors.initials: KM
authors.lastname: Choi
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Saw
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: Gianrico F
authors.initials: GF
authors.lastname: Farrugia
authors.forename: David A
authors.initials: DA
authors.lastname: Carlson
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D008063:Thioctic Acid; D019821:Simvastatin; D051547:Heme Oxygenase-1; D001241:Aspirin
keywords: HO-1; alpha lipoic acid; aspirin; heme oxygenase; humans; simvastatin
references.citation: Free Radic Biol Med. 2006 Apr 15;40(8):1313-22
references.pmid: 16631521
references.citation: Circulation. 2004 Sep 7;110(10):1296-302
references.pmid: 15337692
references.citation: Antioxid Redox Signal. 2007 Dec;9(12):2227-39
references.pmid: 17822367
references.citation: J Biol Chem. 2002 May 17;277(20):17950-61
references.pmid: 11880364
references.citation: Diabetes Care. 2006 Nov;29(11):2365-70
references.pmid: 17065669
references.citation: PLoS One. 2013 May 06;8(5):e62618
references.pmid: 23671613
references.citation: J Clin Biochem Nutr. 2011 Mar;48(2):126-33
references.pmid: 21373265
references.citation: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2100-5
references.pmid: 16123320
references.citation: Circulation. 2002 Sep 17;106(12):1447-52
references.pmid: 12234946
references.citation: Gastroenterology. 2006 Apr;130(5):1466-79
references.pmid: 16678560
references.citation: Circulation. 2001 Apr 17;103(15):1933-5
references.pmid: 11306519
references.citation: Circulation. 2004 Sep 28;110(13):1855-60
references.pmid: 15364806
references.citation: Immunol Cell Biol. 2002 Dec;80(6):550-7
references.pmid: 12406389
references.citation: Gastroenterology. 2008 Dec;135(6):2055-64, 2064.e1-2
references.pmid: 18926825
references.citation: Am J Cardiovasc Dis. 2011;1(2):150-8
references.pmid: 22254194
references.citation: Clin Pharmacol Ther. 2010 Feb;87(2):187-90
references.pmid: 19956091
references.citation: J Cardiovasc Magn Reson. 2012 Aug 02;14:55
references.pmid: 22857721
references.citation: Am J Physiol Cell Physiol. 2005 Sep;289(3):C557-63
references.pmid: 15901601
references.citation: Am J Physiol Renal Physiol. 2011 May;300(5):F1180-92
references.pmid: 21289052
references.citation: J Cell Physiol. 2003 Jun;195(3):373-82
references.pmid: 12704646
references.citation: J Biol Chem. 2006 Nov 3;281(44):33422-32
references.pmid: 16945925
references.citation: Biochem Biophys Res Commun. 2003 Dec 12;312(2):507-12
references.pmid: 14637166
references.citation: Diabetes Care. 2008 Feb;31 Suppl 2:S255-61
references.pmid: 18227494
references.citation: Acta Cardiol. 2006 Jun;61(3):295-300
references.pmid: 16869450
references.citation: J Clin Invest. 2007 Feb;117(2):438-47
references.pmid: 17256058
references.citation: Pharmacol Rev. 2008 Mar;60(1):79-127
references.pmid: 18323402
references.citation: Nat Med. 2002 Mar;8(3):240-6
references.pmid: 11875494
references.citation: Kidney Int. 2006 Aug;70(3):432-43
references.pmid: 16775600
references.citation: Exp Gerontol. 2002 Jan-Mar;37(2-3):401-10
references.pmid: 11772527
references.citation: J Cardiovasc Pharmacol Ther. 2010 Dec;15(4):344-8
references.pmid: 20938039
references.citation: J Clin Invest. 1992 Jul;90(1):267-70
references.pmid: 1634613
references.citation: Circulation. 2008 Jan 15;117(2):231-41
references.pmid: 18195184
references.citation: Biochem Biophys Res Commun. 2003 Sep 5;308(4):956-60
references.pmid: 12927812
references.citation: J Am Soc Nephrol. 2012 Jun;23(6):1048-57
references.pmid: 22440905
references.citation: Am J Physiol Cell Physiol. 2005 Sep;289(3):C507-8
references.pmid: 16100387
references.citation: Circulation. 2001 May 29;103(21):2531-4
references.pmid: 11382718
references.citation: Altern Med Rev. 2007 Dec;12(4):343-51
references.pmid: 18069903
references.citation: Diabet Med. 2004 Feb;21(2):114-21
references.pmid: 14984445
references.citation: Aliment Pharmacol Ther. 2013 Oct;38(7):689-702
references.pmid: 23992228
references.citation: Hepatology. 2011 Mar;53(3):935-44
references.pmid: 21374664