Abstract：
Iron overload has been associated with acute/chronic organ failure, but whether iron overload induces liver injury remains unclear. The objectives of this study were to assess the relationship between urinary iron and serum alanine aminotransferase (ALT, a biomarker for liver injury), and investigate the potential mediating roles of lipid peroxidation and oxidative DNA damage in such association. Levels of urinary iron, serum ALT, and urinary biomarkers of lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]) and oxidative DNA damage (8-hydroxy-deoxyguano-sine [8-OHdG]) were measured among 5386 observations of 4220 participants from the Wuhan-Zhuhai cohort. The relationships of urinary iron with serum ALT and risk of hyperALT were evaluated by linear mixed model and logistic regression model, respectively. The mediating roles of 8-iso-PGF2α and 8-OHdG were assessed by mediation analyses. This cross-sectional analysis found that urinary iron was positively associated with ALT (β = 0.032; 95% CI: 0.020, 0.044) and hyperALT prevalence (OR = 1.127; 95% CI: 1.065, 1.192). After 3 years of follow-up, participants with persistent high iron levels had increased risk of developing hyperALT (RR = 3.800; 95% CI: 1.464, 9.972) when compared with those with persistent low iron levels. In addition, each 1% increase in urinary iron was associated with a 0.146% (95% CI: 0.128%, 0.164%) increase and a 0.192% (95% CI: 0.154%, 0.229%) increase in 8-iso-PGF2α and 8-OHdG, respectively. Urinary 8-iso-PGF2α (β = 0.056; 95% CI: 0.039, 0.074) was positively associated with ALT, while the association between 8-OHdG and ALT was insignificant. Furthermore, increased 8-iso-PGF2α significantly mediated 22.48% of the urinary iron-associated ALT increment. Our study demonstrated that iron overload was significantly associated with liver injury, which was partly mediated by lipid peroxidation. Controlling iron intake and regulating lipid peroxidation may help in preventing liver injury.
摘要：
铁过载与急性/慢性器官衰竭有关，但铁超负荷是否会导致肝损伤仍不清楚。本研究的目的是评估尿铁与血清丙氨酸转氨酶（ALT，肝损伤的生物标志物)，并研究脂质过氧化和氧化DNA损伤在此类关联中的潜在介导作用。尿铁水平,血清ALT,在来自武汉-珠海队列的4220名参与者的5386个观察结果中，测量了脂质过氧化（8-异-前列腺素-F2α[8-异-PGF2α]）和氧化性DNA损伤（8-羟基-脱氧鸟苷[8-OHdG]）的尿液生物标志物。采用线性混合模型和logistic回归模型评价尿铁与血清ALT及ALT增高风险的关系,分别。通过中介分析评估了8-异-PGF2α和8-OHdG的中介作用。该横断面分析发现，尿铁与ALT（β=0.032；95％CI：0.020，0.044）和高ALT患病率（OR=1.127；95％CI：1.065，1.192）呈正相关。经过3年的随访，与持续低铁水平的参与者相比,持续高铁水平的参与者发生高ALT的风险增加(RR=3.800;95%CI:1.464,9.972).此外,尿铁每增加1%与0.146%相关(95%CI:0.128%，0.164%）增加，0.192%（95%CI：0.154%，0.229%)增加8-异-PGF2α和8-OHdG，分别。尿8-异-PGF2α(β=0.056;95%CI:0.039,0.074)与ALT呈正相关,而8-OHdG和ALT之间的关联是微不足道的。此外，增加的8-iso-PGF2α显着介导了22.48％的尿铁相关ALT增加。我们的研究表明，铁过载与肝损伤显著相关，部分是由脂质过氧化作用介导的。控制铁的摄入和调节脂质过氧化可能有助于预防肝损伤。
