Co-Exposure to Bisphenols, Parabens, and Antimicrobials and Association with Coronary Heart Disease: Oxidative Stress as a Potential Mediating Factor?

Abstract

Coronary heart disease (CHD) is the leading cause of global morbidity, but the effect of plasticizers and antimicrobial additives on CHD is unknown. Here, we conducted a case–control study to investigate the mediating role of oxidative stress in the association between co-exposure to seven bisphenols, four parabens, triclosan (TCS), triclocarban, and CHD risk in Guangzhou, China. Quantile-based g-computation and weighted quantile sum regression were used to analyze mixture-outcome associations. Quantile-based g-computation showed a positive joint effect of a decile increase in exposure to all examined pollutants on CHD risk (OR: 1.52, 95% CI: 1.25–1.84), with bisphenol A (BPA), bisphenol F (BPF), n-butyl paraben (BuP), and TCS representing major contributors. The results also showed a decile nonmonotonic increase in the exposure mixtures, positively correlated with a 2.22 ng/mL (95% CI: 1.21–3.23 ng/mL) elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG), with BuP, TCS, bisphenol AP (BPAP), and BPF contributing dominantly. Mediation analysis showed that 8-OHdG mediated the relationship between BPA, BPF, BPAP, and TCS, and CHD risk. Moreover, the mediating role of high-density lipoprotein (HDL) between several bisphenols and CHD was also identified. It is yet to be verified, but bisphenols may elevate CHD risk by reducing HDL status and increasing oxidative stress.

Mediating Role of Glucose-Lipid Metabolism in the Association between the Increased Risk of Coronary Heart Disease and Exposure to Organophosphate Esters, Phthalates, and Polycyclic Aromatic Hydrocarbons

“…However, in the case-control design, we are unable to clarify the interaction between statins and DiNP in relation to serum lipids and liver function. In our preliminary analyses which included 69 CHD patients and 146 controls, we did not observe significant between-group difference of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) . The liver is known to be sensitive to DiNP, with prior in vivo experiments performed in a zebrafish model demonstrating that DiNP exposure induces hepatosteatosis via lipogenic and lipolytic pathways .…”

“…Spearman’s correlation coefficient was calculated to assess bivariate correlations between analytes, with correlation coefficients > 7 indicating a high degree of correlation. The concentrations of analytes which fell below the LOD were replaced with a value representing LOD/ 2 , and then log-transformed before exposure-outcome analyses. , Potential confounders, including age, sex, smoking status, and the use of CHD-related medication, were adjusted in all of the subsequent analyses.…”

“…In our preliminary analyses which included 69 CHD patients and 146 controls, we did not observe significant between-group difference of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). 23 The liver is known to be sensitive to DiNP, with prior in vivo experiments performed in a zebrafish model demonstrating that DiNP exposure induces hepatosteatosis via lipogenic and lipolytic pathways. 43 It is important to note that we did not find a relationship between DiNP and oxidative stress in the study population, which is inconsistent with the prospective observation in pregnant women in the United States.…”

“…22 A previous report revealed that CHD patients had significantly elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, relative to healthy adults; the results suggested that this observed increase among CHD patients may be correlated with exposure to environmental phenols. 23 However, the mechanisms explaining the observed links between exposure to PAEs and PAHs and an increased risk of CHD remain unclear. Furthermore, a reliable estimate of how exposure to OFRs impacts the development of CHD remains enigmatic.…”

“…Imbalanced glucose-lipid metabolism, such as increased blood glucose and dyslipidemia, is intricately involved in atherogenesis and accompanies the development of CHD. , Oxidative stress can exacerbate the progress of atherosclerosis by inducing the accumulation of cholesterol, which is carried by oxidized low-density lipoprotein (LDL), and impairing vasorelaxation . A previous report revealed that CHD patients had significantly elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, relative to healthy adults; the results suggested that this observed increase among CHD patients may be correlated with exposure to environmental phenols . However, the mechanisms explaining the observed links between exposure to PAEs and PAHs and an increased risk of CHD remain unclear.…”