Elsevier

Environmental Research

Volume 109, Issue 6, August 2009, Pages 797-801
Environmental Research

Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women

https://doi.org/10.1016/j.envres.2009.04.014Get rights and content

Abstract

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. There is increasing health concerns regarding low-level exposure to BPA among the general population. The aim of this study was to determine the association between BPA exposure with oxidative stress and inflammation in adult populations. A cross-sectional study was conducted. This study included 485 adults (259 men, 92 premenopausal women, and 134 postmenopausal women) living in general communities within large cities. Urinary concentrations of BPA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), white blood cell (WBC) count, and C-reactive protein (CRP) were measured. Multivariate analyses were applied to determine the associations of BPA exposure with oxidative stress and inflammation. The geometric means of urinary BPA for men, premenopausal women, and postmenopausal women were 0.53, 0.61, and 0.58 μg/g cr, respectively. The urinary BPA concentrations were positively associated with MDA, 8-OHdG, and CRP levels in the postmenopausal women; however, such associations did not exist in men and premenopausal women. The findings of this study suggest that BPA exposure would promote oxidative stress and inflammation, in which postmenopausal women are likely to be more susceptible to BPA-induced health effects.

Introduction

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide and has been used in the chemical industry for the production of polycarbonate plastics and epoxy resins. The polycarbonate plastics are commonly used for packaging food and manufacturing products, such as plastic bottles, compact disks, and automotive lenses. Epoxy resins are used in the linings of food cans, protective coatings and finishes, as well as dental sealants and bonding agents. Accordingly, widespread and continuous exposure of humans to BPA is evident, showing that >92% of urine samples have detectable concentrations of BPA in the US population (Calafat et al., 2008).

Regarding the health effects of BPA, animal studies have provided evidence on lowering sperm motility and count (Chitra et al., 2003), stimulating prolactin release (Steinmetz et al., 1997), and promoting cell proliferation in a breast cancer cell line (Krishnan et al., 1993). Furthermore, disruption of thyroid hormone activity (Moriyama et al., 2002; Zoeller et al., 2005) and antagonistic androgen action have been suggested (Lee et al., 2003). In humans, reports have highlighted the association of BPA with medical disorders, such as diabetes, liver enzyme abnormalities, polycystic ovarian syndrome (Takeuchi et al., 2004), and recurrent miscarriage (Sugiura-Ogasawara et al., 2005).

It has been suggested that BPA functions either estrogenically or anti-estrogenically, while binding to both estrogen receptor (ER)-α and -β (Hiroi et al., 1999; Kurosawa et al., 2002), in which BPA competes with estradiol (Kuiper et al., 1998). The relative binding affinity of BPA to ER is known to be more than 1000 times weaker than that of estradiol. Nevertheless, there is some evidence that BPA stimulates cellular responses at very low concentrations through various pathways (Gould et al., 1998; Iso et al., 2006; Welshons et al., 2006). In terms of transcriptomal actions, xenoestrogens, but not 17β-estradiol, have been reported to enhance expression of genes in mitochondrial oxidative phosphorylation (Shioda et al., 2006).

The action of BPA may be explained by occupancy and activation of the ER (Thomson et al., 2003). Ishunina et al. (2000) reported that expression of ER-α and -β differs by gender and aging in the human supraoptic nucleus. Thus, it is plausible to assume that the effects of BPA on health issues would be different by gender and menopausal status due to the difference in the expression of the ER and/or the receptor occupancy.

Inflammation is an important part of the body's defense mechanisms and a dynamic response of vascularized tissues to injury, although excessive inflammation can also lead to various diseases, including cancer and cardiovascular disease (Mahadik et al., 2008). Oxidative stress is a key component of inflammatory reactions and considered to be an important pathophysiologic process. BPA has been known to induce oxidative stress by decreasing antioxidant enzymes and increasing hydrogen peroxide and lipid peroxidation in the liver and epididymal sperm of rats (Bindhumol et al., 2003). In previous studies, oxidative stress had been shown to be responsible for adverse effects of BPA regarding male reproduction (Chitra et al., 2003) and underdevelopment of the kidney, brain, and testis in mice (Kabuto et al., 2004). It is not known, however, whether BPA is associated with either oxidative stress or inflammation markers in humans.

Malondialdehyde (MDA), a widely used indicator of lipid peroxidation, has been considered as a potential biomarker for oxidative stress. Another oxidative stress marker is 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA oxidation (Kasai, 1997; Loft et al., 1993). White blood cell (WBC) counts and C-reactive protein (CRP) levels are inflammation markers associated with the development of cardiovascular events. The present study investigated the role of urinary BPA concentration on oxidative stress measured by urinary MDA and 8-OhdG levels and inflammation assessed by blood WBC counts and serum CRP levels.

We hypothesized that the relationship between the BPA level with either oxidative stress or inflammation is different with respect to gender and menopausal status due to differences in the expression of the ER and/or the ER occupancy. To test this hypothesis, three different adult population groups (adult men, and pre- and postmenopausal women) were studied.

Section snippets

Participants

A total of 1131 adults were enrolled for the Biomarker Monitoring for Environmental Health between April and December 2005, of which urinary BPA was analyzed in 613 subjects. Of the 613 individuals, this study excluded subjects who reported a history of diseases possibly influencing oxidative stress levels, such as cancer, ischemic heart disease, cerebrovascular accidents, tuberculosis, acute hepatitis, chronic bronchitis, arthritis, or asthma. We further excluded 4 women who had occasional

Results

Urinary BPA concentrations were detected in three-fourths of the subjects. The distributions of urinary BPA concentrations were similar among the three groups, except at the extremes. The BPA concentration at the 95th percentile in men was more than 3-fold higher than the value for premenopausal women (Table 1).

The characteristics of the subjects and the associations with urinary BPA concentrations are shown in Table 2. Age was positively associated with urinary BPA concentration, but no such

Discussion

In the present study, BPA exposure was clearly associated with oxidative stress and inflammatory markers in postmenopausal women, but not in premenopausal women and adult men. This result suggests that the effects of BPA on health would be different by gender and menopausal status.

The geometric means of the urinary BPA concentrations found in this study were lower than the range reported previously in adults, although comparisons across studies are limited by differences in the methods used to

Acknowledgments

YCH, JHL and EHA designed the overall study, obtained funding, provided the definition of the variables, and were responsible for overseeing the data collection; YJY, YCH and SYO, MSP, HK designed the study for this manuscript; YJY and SYO were responsible for data analyses; YJY and SYO wrote the manuscript draft; and YCH, MSP, HK, JHL, and EHA provided critical reviews. None of the authors had a conflict of interest related to the data in the manuscript.

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    The present study was supported by the Eco-technopia 21 project of Korea Institute of Environmental Science and Technology. This study was approved by the Institutional Review Boards of the Ewha Womans’ University Hospital and Inha University Hospital. Signed informed consent was obtained from all the participants.

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