Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.

Journal

ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411

Informations de publication

Date de publication:
09 Apr 2021
Historique:
received: 07 01 2021
entrez: 16 4 2021
pubmed: 17 4 2021
medline: 17 4 2021
Statut: epublish

Résumé

Sterol biosynthesis is a critical homeostatic mechanism of the body. Sterol biosynthesis begins during early embryonic life and continues throughout life. Many commonly used medications, prescribed >200 million times in the United States annually, have a sterol biosynthesis inhibition side effect. Using our high-throughput LC-MS/MS method, we assessed the levels of post-lanosterol sterol intermediates (lanosterol, desmosterol, and 7-dehydrocholesterol (7-DHC)) and cholesterol in 1312 deidentified serum samples from pregnant women. 302 samples showing elevated 7-DHC were analyzed for the presence of 14 medications known to inhibit the 7-dehydrocholesterol reductase enzyme (DHCR7) and increase 7-DHC. Of the 302 samples showing 7-DHC elevation, 43 had detectable levels of prescription medications with a DHCR7-inhibiting side effect. Taking more than one 7-DHC-elevating medication in specific combinations (polypharmacy) might exacerbate the effect on 7-DHC levels in pregnant women, suggesting a potentially additive or synergistic effect. As 7-DHC and 7-DHC-derived oxysterols are toxic, and as DHCR7-inhibiting medications are considered teratogens, our findings raise potential concerns regarding the use of prescription medication with a DHCR7-inhibiting side effect during pregnancy. The use of prescription medications during pregnancy is sometimes unavoidable, but choosing a medication without a DHCR7-inhibiting side effect might lead to a heathier pregnancy and prevent putatively adverse outcomes for the developing offspring.

Identifiants

DOI: 10.1021/acsptsci.1c00012 PMID: 33860207 PMC: PMC8033759
pubmed: 33860207
doi: 10.1021/acsptsci.1c00012
pmc: PMC8033759
doi:

Types de publication

Journal Article

Langues

eng

Pagination

848-857

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD064727
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH067234
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110636
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115458
Pays : United States

Informations de copyright

© 2021 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Références

J Am Chem Soc. 2009 Sep 16;131(36):13037-44
pubmed: 19705847
J Lipid Res. 2010 Dec;51(12):3399-413
pubmed: 20861164
Am J Obstet Gynecol. 2013 Apr;208(4):301.e1-6
pubmed: 23159698
Curr Opin Lipidol. 2001 Apr;12(2):105-12
pubmed: 11264981
ACS Chem Neurosci. 2021 Feb 17;12(4):735-745
pubmed: 33528983
Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R75-88
pubmed: 12668600
Am J Obstet Gynecol. 2011 Jul;205(1):51.e1-8
pubmed: 21514558
J Lipid Res. 2011 Jan;52(1):6-34
pubmed: 20929975
J Inherit Metab Dis. 2013 Jan;36(1):113-22
pubmed: 22718275
Mol Psychiatry. 2020 Nov;25(11):2685-2694
pubmed: 32504050
J Inherit Metab Dis. 2019 Sep;42(5):934-943
pubmed: 30891795
Endocr Rev. 2004 Dec;25(6):947-70
pubmed: 15583024
Mol Biol Cell. 2006 Apr;17(4):1593-605
pubmed: 16452637
Toxicol Appl Pharmacol. 2018 Jun 15;349:21-28
pubmed: 29698737
Pharmacogenomics J. 2016 Oct;16(5):411-29
pubmed: 27401223
Schizophr Res. 2017 Sep;187:74-81
pubmed: 28202290
MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):66-70
pubmed: 29346342
J Clin Invest. 2002 Sep;110(6):715-24
pubmed: 12235098
J Lipid Res. 2017 Nov;58(11):2139-2146
pubmed: 28972118
J Lipid Res. 2014 Feb;55(2):329-37
pubmed: 24259532
J Am Chem Soc. 2010 Feb 24;132(7):2222-32
pubmed: 20121089
J Clin Psychopharmacol. 2011 Aug;31(4):531-2
pubmed: 21720228
MMWR Morb Mortal Wkly Rep. 2016 Jan 29;65(3):41-6
pubmed: 26821271
J Med Genet. 2005 Feb;42(2):e17
pubmed: 15689440
Mol Genet Metab. 2013 Sep-Oct;110(1-2):176-8
pubmed: 23628460
J Clin Psychopharmacol. 2007 Dec;27(6):720-2
pubmed: 18004149
Am J Med Genet C Semin Med Genet. 2011 Aug 15;157C(3):175-82
pubmed: 21766440
J Pediatr. 1964 Feb;64:210-7
pubmed: 14119520
J Med Chem. 2016 Feb 11;59(3):1102-15
pubmed: 26789657
Environ Health Perspect. 2020 Jan;128(1):17014
pubmed: 31985273
Mol Psychiatry. 2019 Apr;24(4):491-500
pubmed: 30742019
Eur J Hum Genet. 2011 Sep;19(9):942-6
pubmed: 21559050
J Atten Disord. 2020 Feb;24(3):479-489
pubmed: 29519207
Transl Psychiatry. 2021 Feb 1;11(1):85
pubmed: 33526772
Am J Med Genet. 1999 Mar 19;83(3):213-9
pubmed: 10096601
Am J Obstet Gynecol. 2012 Nov;207(5):405.e1-7
pubmed: 22917484
J Lipid Res. 2018 Oct;59(10):1916-1926
pubmed: 30087204
Pharmacoepidemiol Drug Saf. 2013 Sep;22(9):1013-8
pubmed: 23893932
J Lipid Res. 2006 Jul;47(7):1535-41
pubmed: 16651660
Genet Med. 2002 Nov-Dec;4(6):434-8
pubmed: 12509714
Neuropharmacology. 2008 Dec;55(8):1265-73
pubmed: 18402986
J Clin Psychopharmacol. 2010 Apr;30(2):204-5
pubmed: 20520299
Chem Phys Lipids. 2016 Sep;199:136-143
pubmed: 27179407
Am J Obstet Gynecol. 2008 Feb;198(2):191.e1-7
pubmed: 18226621
Neurobiol Dis. 2012 Mar;45(3):923-9
pubmed: 22182693
Am J Med Genet. 2000 Feb 14;90(4):339-46
pubmed: 10710235
Am J Obstet Gynecol. 2005 Sep;193(3 Pt 1):771-7
pubmed: 16150273
J Lipid Res. 2013 Apr;54(4):1135-43
pubmed: 23381570
Matern Child Health J. 2018 Jan;22(1):92-100
pubmed: 28900803
Mol Genet Metab. 2000 Sep-Oct;71(1-2):163-74
pubmed: 11001807
Matern Child Health J. 2015 May;19(5):1097-106
pubmed: 25287251
Chem Rev. 2011 Oct 12;111(10):6423-51
pubmed: 21902244
J Lipid Res. 2011 Oct;52(10):1810-20
pubmed: 21817059
Clin Genet. 2015 Jun;87(6):570-5
pubmed: 24813812
J Lipid Res. 2004 Aug;45(8):1375-97
pubmed: 15254070
J Lipid Res. 2010 Nov;51(11):3259-69
pubmed: 20702862
J Biol Chem. 2011 Aug 19;286(33):29086-29097
pubmed: 21705796
J Mol Histol. 2019 Feb;50(1):63-73
pubmed: 30535733
Psychiatry Res. 2013 Dec 30;210(3):901-5
pubmed: 23993464
Arch Ophthalmol. 2004 Aug;122(8):1190-200
pubmed: 15302661
Eur J Hum Genet. 2008 May;16(5):535-41
pubmed: 18285838
Birth Defects Res. 2019 Jun 1;111(10):613-620
pubmed: 30891943
Chem Res Toxicol. 2016 May 16;29(5):892-900
pubmed: 27097157
Free Radic Res. 2015;49(7):835-49
pubmed: 25381800
J Lipid Res. 2011 Jun;52(6):1222-1233
pubmed: 21402677

Auteurs

Thiago C Genaro-Mattos (TC)

Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States.

Korinne B Klingelsmith (KB)

Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States.

Luke B Allen (LB)

Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Allison Anderson (A)

Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States.

Keri A Tallman (KA)

Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37221, United States.

Ned A Porter (NA)

Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37221, United States.

Zeljka Korade (Z)

Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Károly Mirnics (K)

Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Classifications MeSH