Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation

Steven G. Carmella, Alisa K. Heskin, Mei Kuen Tang, Joni Jensen, Xianghua Luo, Chap T. Le, Sharon E. Murphy, Neal L. Benowitz, F. Joseph McClernon, Ryan Vandrey, Sharon S. Allen, Rachel Denlinger-Apte, Paul M. Cinciripini, Andrew A. Strasser, Mustafa Al’Absi, Jason D. Robinson, Eric C. Donny, Dorothy K. Hatsukami, Stephen S. Hecht

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl] cyclopentyl]hept-5-enoic acid (8-iso-PGF ), an F2-isoprostane and biomarker of oxidative damage, and “prostaglandin E 2 metabolite” (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

Original languageEnglish (US)
Article numbere0215853
JournalPloS one
Issue number4
StatePublished - Apr 2019

Bibliographical note

Funding Information:
This work was supported by National Institute on Drug Abuse and Food and Drug Administration grant U54 DA-031659 (ECD, DKH, CTL, and SSH). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors are indebted to the contributions of the Masonic Cancer Center Analytical Biochemistry Shared Resource, which provided mass spectrometry support essential for this study. The Shared Resource is supported in part by National Cancer Institute Cancer Center Support Grant CA-077598.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

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