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Urinary polycyclic aromatic hydrocarbon metabolites and Crohn's disease activity: the mediating role of oxidative
Shu Xu1, Liangle Yang2, Yapan Liu3
1Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. zhuliangru@hust.edu.cn.
Background:
Exposure to polycyclic aromatic hydrocarbons (PAHs) may result in chronic inflammation. However, the impact of PAHs on the inflammatory activity of Crohn's disease (CD) and the potential mechanism remain unclear. We explored the relationship between PAH exposure and disease activity in CD patients and evaluated the underlying mediating role of oxidative stress.
Methods:
A total of 127 adult CD patients at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, were included in this study. Ten urinary monohydroxylated PAHs (OH-PAHs), two urinary oxidative stress biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α)], and four CD activity indices [Crohn's disease Harvey-Bradshaw index (HBI), body mass index (BMI), simplified endoscopic score for Crohn's disease (SES-CD), and computed tomography enterography score (CTE)] were assessed. After adjusting for possible confounders, multivariate linear regression analyses were performed to examine the associations of urinary OH-PAHs with CD activity and oxidative stress, and oxidative stress with CD activity. Mediation analyses were conducted to estimate the mediating role of oxidative stress in the relationship between urinary OH-PAHs and CD activity.
Results:
With a doubling increase in certain urinary OH-PAHs, HBI increased (3-OHPh 13.0% [3.1%, 23.7%], 4-OHPh 16.2% [5.4%, 28.3%], and 2-OHFlu 10.6% [0.2%, 22.1%]) while BMI decreased (3-OHPh 3.4% [-5.8%, -1.0%], 4-OHPh 5.1% [-7.5%, -2.6%], 9-OHPh 3.3% [-5.7%, -1.0%], 2-OHFlu 3.4% [-5.9%, -0.8%], 1-OHP 1.2% [-2.1%, -0.2%], ΣOHPh 3.1% [-5.8%, -0.4%], ΣOHFlu 3.3% [-6.3%, -0.3%], and ΣOH-PAHs 2.7% [-5.3%, -0.1%]) in CD patients in an exposure-response manner. Meanwhile, almost all urinary OH-PAHs were dose-dependently associated with elevated urinary 8-OHdG and 8-iso-PGF2α, both of which were also associated with the increased HBI and decreased BMI. Further mediation analyses showed that the oxidative stress mediated 61.9-91.8% of the associations of urinary OH-PAHs with HBI and BMI.
Conclusion:
PAH exposure results in enhanced disease activity in CD patients. Mechanically, oxidative stress could be a mediator linking the PAH exposure and CD activity.
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