Abstract

The urinary metabolites “prostaglandin E2 metabolite” (PGE-M) and (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α) are biomarkers of inflammation and oxidative damage, respectively, and are elevated in cigarette smokers. Relatively little is known about the effects of smoking cessation on these biomarkers. To investigate this, current cigarette smokers interested in quitting were recruited and invited to participate in a smoking cessation study where varenicline (Chantix) and brief supportive behavioral counseling were offered at each visit after baseline. Subjects returned to the clinic during the 12 week treatment phase for 9 visits post cessation on days 3, 7, 14, 21, 28, 42, 56, 70 and 84. Urine samples were collected at each visit and analyzed by liquid chromatography-tandem mass spectrometry for PGE-M, 8-iso-PGF2α, and cotinine. Cotinine values demonstrated that 15 of 38 subjects quit smoking for the entire 84 day period. Significant decreases in mean levels of PGE-M and 8-iso-PGF2α per milligram creatinine were observed in these subjects, by 44% (p = 0.0014) and 27% (p<0.001), respectively. The results of this study demonstrate that cessation of smoking for 84 days results in modest but significant declines in urinary PGE-M and 8-iso-PGF2α indicating reductions in systemic inflammation and oxidative damage. Given that levels were only modestly decreased, these markers are not specific to tobacco-smoke exposure. The modest declines in these biomarkers should be considered when planning studies with ex-smokers. There is a “hangover” from smoking that lasts at least 3 months.

Highlights

  • Data from 15 subjects were analyzed after exclusion of non-smokers, very light smokers, or subjects who did not stop smoking based on inspection of the decrease in urinary cotinine over the course of the study, typically to less than 15 ng/ml (Table 1)

  • Two PGE-M values, no 8iso-PGF2α values, and 22 cotinine values were below the limit of detection (LOD)

  • Sex and age were not associated with either day 56 residual metabolite (p > 0.05), and race was associated with only PGE-M (p = 0.01)

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Summary

Introduction

Inflammation and oxidative damage, which are closely related and interlinked phenomena, are significant factors in diseases caused by cigarette smoking including cancer, cardiovascularPLOS ONE | https://doi.org/10.1371/journal.pone.0218386 June 28, 2019Smoking cessation and biomarkers of inflammation and oxidative damageMasonic Cancer Center, supported in part by National Cancer Institute Cancer Center Support Grant (CA-077598). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

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