Wang Pei-Wei, Chen Mei-Lien, Huang Li-Wei, Yang Winnie, Wu Kuen-Yuh, Huang Yu-Fang
a Department of Pediatrics , Taipei City Hospital, Heping Fuyou Branch , Taipei , Taiwan.
b Institute of Environmental and Occupational Health Sciences, National Yang Ming University , Taipei , Taiwan.
Free Radic Res. 2015;49(12):1469-78. doi: 10.3109/10715762.2015.1088644.
Animal studies have shown that exposure to nonylphenol (NP) increases oxidative/nitrative stress, but whether it does so in humans is unknown. This study examines prenatal exposure to NP and its effects on oxidatively/nitratively damaged DNA, lipid peroxidation, and the activities of antioxidants. A total of 146 urine and blood specimens were collected during gestational weeks 27-38 and hospital admission for delivery, respectively. Urinary NP was analyzed by high-performance liquid chromatography (HPLC). Urinary biomarkers of oxidatively/nitratively damaged DNA and lipid peroxidation, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-nitroguanine (8-NO(2)Gua), 8-iso-prostaglandin F(2α) (8-isoPF(2α)) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), were simultaneously analyzed using isotope-dilution liquid-chromatography/electron spray ionization tandem mass spectrometry. The activities of maternal plasma superoxide dismutase and glutathione peroxidase were analyzed by enzyme-linked immunosorbent assay. Urinary NP level was significantly associated with 8-oxodG and 8-NO(2)Gua levels in late pregnancy, suggesting that NP may enhance oxidatively and nitratively damaged DNA. The adjusted odds ratios for high 8-oxodG level exhibited a significantly dose-response relationship with NP levels, stratified into four quartiles. 8-oxodG appears to be a more sensitive and effective biomarker of NP exposure than 8-NO(2)Gua. These relationships suggest NP may play a role in the pregnancy complications.
动物研究表明,接触壬基酚(NP)会增加氧化/硝化应激,但在人类中是否如此尚不清楚。本研究检测了孕期接触NP的情况及其对氧化/硝化损伤的DNA、脂质过氧化和抗氧化剂活性的影响。分别在妊娠第27 - 38周和入院分娩时收集了146份尿液和血液样本。采用高效液相色谱法(HPLC)分析尿中NP。同时使用同位素稀释液相色谱/电喷雾电离串联质谱法分析氧化/硝化损伤的DNA和脂质过氧化的尿生物标志物,包括8 - 氧代 - 7,8 - 二氢 - 2'- 脱氧鸟苷(8 - oxodG)、8 - 硝基鸟嘌呤(8 - NO₂Gua)、8 - 异前列腺素F₂α(8 - isoPF₂α)和4 - 羟基 - 2 - 壬烯醛 - 巯基尿酸(HNE - MA)。通过酶联免疫吸附测定法分析母体血浆超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。妊娠晚期尿NP水平与8 - oxodG和8 - NO₂Gua水平显著相关,提示NP可能增强氧化和硝化损伤的DNA。将8 - oxodG水平分为四个四分位数,其调整后的优势比与NP水平呈现显著的剂量反应关系。8 - oxodG似乎是比8 - NO₂Gua更敏感有效的NP暴露生物标志物。这些关系表明NP可能在妊娠并发症中起作用。