The association between bisphenol A exposure and oxidative damage in rats/mice: A systematic review and meta-analysis

https://doi.org/10.1016/j.envpol.2021.118444Get rights and content

Highlights

  • BPA could cause oxidative damage by significantly increasing oxidant levels and reducing antioxidant levels in rats/mice.

  • Tissue type in rats/mice, BPA intervention means, dose, and duration were related to oxidative damage indicators levels.

  • The results provided clear evidence for the clarification and prevention of BPA-induced oxidative damage.

Abstract

Numerous studies reported that BPA could cause oxidative damage to different tissues in rats/mice. This study aimed to perform a systematic review and meta-analysis of BPA exposure on oxidative damage in rats/mice. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science databases from their inception date until July 18, 2020. 20 eligible articles were included in this study. The results showed that BPA could significantly increase the level of MDA (SMD, 16.88; 95%CI, 12.06–21.71), but there was a significant reduction in the contents of antioxidants, such as GR (−10.46, −13.91 ∼ −7.02), CAT (−8.48, −11.66 ∼ −5.30), GPx (−9.37, −11.95 ∼ −6.80), GST (−7.59, −14.51 ∼ −0.67), GSH (−10.64, −13.96 ~ −7.33), and SOD (−6.48, −8.37 ∼ −4.58) in rats/mice. Our study provided clear evidence that BPA exposure could significantly induce oxidative damage in rats/mice. And we also found that the degree of oxidative damage was related to BPA dose, target tissue, intervention means, and exposure duration of BPA.

Introduction

Bisphenol A (BPA), a typical endocrine-disrupting chemical, is widely used in the manufacture of polycarbonate plastics, epoxy resins, paints, food packaging, and dental sealants (Hwang et al., 2018). Human beings have been exposed to BPA via various routes such as oral, inhalation, and transdermal (Zhang et al., 2014) which leads to the detection of BPA in human blood, urine, breast milk, amniotic fluid, and other tissues (Guo et al., 2021; Kang et al., 2020; Mokra et al., 2015). A number of studies have illustrated that exposure to BPA was associated with multiple deleterious health effects for animals and humans. Evidence from animal studies has demonstrated that BPA could cause developmental defects in reproductive tissues (Ullah et al., 2018), neurological impairment (Yu et al., 2020), and immune system toxicity in rodents (Moreman et al., 2017; Wang et al., 2020), and induce embryo development disorder, estrogenic effects, thyroid toxicity (Pelayo et al., 2012) and testicular toxicity on aquatic species (Canesi and Fabbri, 2015). Human studies have also reported the relationship between BPA exposure and adverse health outcomes including cardiovascular pathologies (Zhang et al., 2020), obesity (Legler et al., 2015), hypertension (Abraham and Chakraborty, 2020), and so on. Additionally, several emerging epidemiological studies have offered further evidence for the toxicity of BPA. In terms of reproductive and developmental disorders, BPA exposure might lead to an increased sperm DNA fragmentation index in young men (Kiwitt-Cárdenas et al., 2021). And prenatal BPA exposure had sexually dimorphic effects on birth length and ponderal index in infants (Yang et al., 2021). For type 2 diabetes, positive associations between exposure to BPA and the incidence of type 2 diabetes have been found (Rancière et al., 2019).

Studies have shown that multiple underlying molecular mechanisms are involved in BPA-induced toxicities, but oxidative stress is one of the main mechanisms (Liang et al., 2020). Oxidative stress is an imbalance between oxidative and antioxidant homeostasis in the body, and a vital part of inflammatory reactions (Lenaz, 2012). Therefore, oxidative stress involves the development of many disorders such as chronic nephrosis, cardiovascular disease, hepatic inflammation, hypercholesterolemia, neurodegenerative diseases, diabetes, etc.(Chai et al., 2019; Samarghandian et al., 2017). There is growing evidence that BPA toxicity is associated with oxidative stress and related markers in several experimental models (Gassman, 2017) and in humans (Yang et al., 2009). The production of oxidants and/or decreased capacity of antioxidant defense significantly promotes BPA toxicity, altering the oxidative balance in the mitochondria and intracellular (Gassman, 2017; Meli et al., 2020). Animal studies have indicated that BPA could cause liver damage by oxidative stress (Rönn et al., 2013) and could induce oxidative stress in other vital organs like the kidney, ovary, and testis (Avci et al., 2016; Elobeid and Hassan, 2015; Zahra et al., 2020). In human populations, several studies have also reported associations between BPA exposure and oxidative stress. Exposure to BPA might partly contribute to the elevated levels of oxidative stress markers in the urine of adult men (Wang et al., 2019). Maternal exposure to BPA was associated with an increase in biomarkers of oxidative stress, which might mediate adverse birth outcomes and/or fetal development (Ferguson et al., 2016). Additionally, exposure to BPA might be related to immune imbalance and oxidative stress in patients with unexplained recurrent spontaneous abortion (URSA) (Liang et al., 2020).

Glutathione disulfide (GSSG), malondialdehyde (MDA), hydrogen peroxide (H2O2), reactive oxygen species (ROS) levels are positively correlated with the degree of oxidative damage. Superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), glutathione-s-transferase (GST), and reduced glutathione (GSH) are antioxidant indicators involved in the control of the redox balance of cells. A large number of researches have been conducted on the oxidative stress of BPA in rats/mice. Due to the diverse tissues selected by investigators in BPA toxicity studies, as well as the doses and durations of BPA exposure, there were some differences in the extent of BPA-caused oxidative damage in various studies. It was reported that the levels of MDA and SOD did not change significantly in the liver and kidney of mice and rats after BPA exposure, but BPA has led to the decreased activities of SOD while increasing MDA levels in spleens of mice. (Dong et al., 2013; Elobeid and Hassan, 2015). In addition, some articles have proved that the level of MDA upregulated dramatically after exposure to BPA in hepatic and BPA exposure could reduce the level of SOD in ovarian of rats (Elswefy et al., 2016; Ijaz et al., 2020). Moreover, systematic evaluations of oxidative damage in rats/mice by BPA exposure have not been reported. Therefore, a systematic review focusing on oxidative damage caused by BPA is warranted.

Our study aimed to perform an updated systematic review and meta-analysis, expecting to provide some evidence for the oxidative damage caused by BPA exposure.

Section snippets

Methods

This systematic review and meta-analysis was in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (Moher et al., 2010). We registered the protocol on PROSPERO with the registration number CRD42020205157. The cord can be found at http://www.crd.york.ac.uk/PROSPERO. The first step in a systematic review is to define the protocol through a Population (including animal species)-Exposure-Comparator-Outcome (PECO) statement (Morgan et al., 2018;

Characteristics of included studies

According to the search strategy, 763 publications were preliminarily retrieved from the database. Following the exclusion of non-eligible articles, 20 studies met the inclusion criteria and were included in the meta-analysis (Fig. 1). All studies used rats and mice as animal models. BPA intervention means were gavage and orally. The dose of BPA ranged from 10 mg/kg to 240 mg/kg, and the experimental duration varied from 14 days to 70 days. Target tissues included liver, testicle, kidney,

Discussion

As an important environmental endocrine disruptor, BPA has been detected in many normal human tissues such as serum (Guo et al., 2021), breast milk (Lee et al., 2018), amniotic fluid (Vandenberg et al., 2012), urine (Huang et al., 2017), saliva and adipose tissue (Berge et al., 2019). The detrimental effects of BPA have been described in many epidemiological and animal studies. BPA may cause immune system problems, adverse reproductive (Zhang et al., 2017) and developmental effects, changes in

Conclusions

Although the study has some limitations, the current meta-analysis still highlighted that BPA could induce oxidative damage by significantly increasing oxidants levels and decreasing antioxidants levels in rats/mice. BPA intervention means, dose and duration, and type of tissue in rats/mice were related to the levels of oxidative stress indicators. The results of the present study provided reliable evidence for clarifying the oxidative damage induced by BPA. Future studies on specific

Author statement

Huan Zhang: Software, Writing - Original Draft, Data Curation.

Wanying Shi: Investigation, Project administration.

Xin Zhou: Investigation, Data Curation.

Suju Sun: Supervision, Conceptualization, Writing - Review & Editing.

Ruifu Yang: Supervision, Writing - Review & Editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors acknowledge all the participants and administrators of this study.

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