Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects

Adil Eddie Bharucha, Kyoung Moo Choi, Jessica J. Saw, Simon J. Gibbons, Gianrico Farrugia, David A. Carlson, Alan R. Zinsmeister

Research output: Contribution to journalArticle

7 Citations (Scopus)

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. Key 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 & Inferences: 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.

Original languageEnglish (US)
Pages (from-to)1437-1442
Number of pages6
JournalNeurogastroenterology and Motility
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

Thioctic Acid
Heme Oxygenase-1
Simvastatin
Aspirin
Healthy Volunteers
Proteins
simvastatin acid
Placebos
Monocytes
Gastroparesis
Placebo Effect
Hemin
Ileus
Colitis
Heme
Human Activities
Pancreatitis

Keywords

  • Alpha lipoic acid
  • Aspirin
  • Heme oxygenase
  • HO-1
  • Humans
  • Simvastatin

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects. / Bharucha, Adil Eddie; Choi, Kyoung Moo; Saw, Jessica J.; Gibbons, Simon J.; Farrugia, Gianrico; Carlson, David A.; Zinsmeister, Alan R.

In: Neurogastroenterology and Motility, Vol. 26, No. 10, 01.10.2014, p. 1437-1442.

Research output: Contribution to journalArticle

Bharucha, Adil Eddie ; Choi, Kyoung Moo ; Saw, Jessica J. ; Gibbons, Simon J. ; Farrugia, Gianrico ; Carlson, David A. ; Zinsmeister, Alan R. / Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects. In: Neurogastroenterology and Motility. 2014 ; Vol. 26, No. 10. pp. 1437-1442.
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T1 - Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects

AU - Bharucha, Adil Eddie

AU - Choi, Kyoung Moo

AU - Saw, Jessica J.

AU - Gibbons, Simon J.

AU - Farrugia, Gianrico

AU - Carlson, David A.

AU - Zinsmeister, Alan R.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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. Key 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 & Inferences: 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.

AB - 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. Key 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 & Inferences: 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.

KW - Alpha lipoic acid

KW - Aspirin

KW - Heme oxygenase

KW - HO-1

KW - Humans

KW - Simvastatin

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