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

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-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and “prostaglandin E2 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-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α 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-PGF2α 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-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α 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.

尿液代谢物(Z)-7-[1R,2R,3R,5S)-3,5-二羟基-2-[(E,3S)-3-羟基辛-1-烯基]环戊基]庚-5-烯酸（8-iso-PGF2α）属于F2-异前列腺素，是氧化损伤的生物标志物；而前列腺素E2代谢物（PGE-M）则是炎症的生物标志物，二者在吸烟者体内的水平均升高。然而，现有文献中关于这类广泛使用的生物标志物的纵向稳定性的相关信息十分匮乏。
在一项涵盖10家机构研究中心的大型临床试验中，研究为受试者免费提供为期20周的Spectrum NRC600/601型研究用卷烟，该卷烟尼古丁含量为15.5 mg/g烟草。所有受试者需在整个研究期间使用该卷烟进行吸烟。在第4、8、12、16及20周时，研究人员收集受试者的晨尿样本，并采用经过验证的液相色谱-电喷雾电离串联质谱法对8-iso-PGF2α与PGE-M进行检测分析。
第4周时，8-iso-PGF2α的平均水平为1.34 ± 1.08（S.D.）pmol/mg肌酐（N=226），同期PGE-M的平均水平为73.7 ± 113（S.D.）pmol/mg肌酐（N=232）。第20周时，8-iso-PGF2α的对应水平为1.35 ± 0.93（S.D.）pmol/mg肌酐（N=209），PGE-M的对应水平为74.2 ± 142（S.D.）pmol/mg肌酐（N=210）。上述指标在中间各随访周均存在一定波动。
8-iso-PGF2α与PGE-M的组内相关系数（intra-class correlation coefficients, ICC）分别为0.51（95%置信区间：0.45~0.57）与0.36（0.30~0.43），提示在吸烟者中，8-iso-PGF2α的纵向稳定性尚可，而PGE-M的纵向稳定性较差。两类生物标志物的ICC值均为男性高于女性。
上述结果表明，除吸烟外，内源性氧化损伤与炎症过程同样会影响当前吸烟者体内这类生物标志物的水平随时间的变化。