Oxidative Stress and BPA Toxicity: An Antioxidant Approach for Male and Female Reproductive Dysfunction

Abstract

Bisphenol A (BPA) is a non-persistent anthropic and environmentally ubiquitous compound widely employed and detected in many consumer products and food items; thus, human exposure is prolonged. Over the last ten years, many studies have examined the underlying molecular mechanisms of BPA toxicity and revealed links among BPA-induced oxidative stress, male and female reproductive defects, and human disease. Because of its hormone-like feature, BPA shows tissue effects on specific hormone receptors in target cells, triggering noxious cellular responses associated with oxidative stress and inflammation. As a metabolic and endocrine disruptor, BPA impairs redox homeostasis via the increase of oxidative mediators and the reduction of antioxidant enzymes, causing mitochondrial dysfunction, alteration in cell signaling pathways, and induction of apoptosis. This review aims to examine the scenery of the current BPA literature on understanding how the induction of oxidative stress can be considered the “fil rouge” of BPA’s toxic mechanisms of action with pleiotropic outcomes on reproduction. Here, we focus on the protective effects of five classes of antioxidants—vitamins and co-factors, natural products (herbals and phytochemicals), melatonin, selenium, and methyl donors (used alone or in combination)—that have been found useful to counteract BPA toxicity in male and female reproductive functions.

Oral Bisphenol A Worsens Liver Immune-Metabolic and Mitochondrial Dysfunction Induced by High-Fat Diet in Adult Mice: Cross-Talk between Oxidative Stress and Inflammasome Pathway

“…Our data agree with previous studies reporting that BPA interferes with mitochondrial functions in the liver and other tissues [7,39] compromising the respiratory chain, reducing OXPHOS capacity, and increasing oxidative stress [34,39]. Moreover, the alteration of mitochondrial bioenergetics, dynamics, and apoptosis by BPA has been recently demonstrated [7,40].…”

“…However, we cannot exclude the involvement of other mechanisms underlying BPA liver toxicity. Among these, oxidative stress caused by BPA exposure can induce epigenetic changes [34], including DNA methylation that modulates metabolic/endocrine processes and diseases [55][56][57]. According to these findings, our preliminary data show the alteration of global DNA hypermethylation by BPA in the liver from obese mice, demonstrating an exacerbation of epigenetic changes induced by HFD ( Figure S1, Supplementary Materials).…”

“…Generally, the toxic effects of the xenobiotics depend on concentration/dose and time of exposure. In preclinical in vivo and in vitro studies planned to explore the molecular mechanisms of EDCs, high doses or concentrations are usually preferred [34,35]. In our experimental condition, we chose 50 µg/kg based on literature data considering the short time of mice exposure to BPA (3 weeks).…”

Role of Antioxidants in Alleviating Bisphenol A Toxicity

“…However, further studies are required to outline their usefulness, optimal dosage, and treatment scheme for countering BPA toxicity. Besides, even many antioxidants such as GSH, vitamin C, vitamin E, N-acetylcysteine, and lipoic acid exhibit potentially beneficial effects to ameliorate BPA toxicity in vitro (reviewed in Meli et al [19]), in many cases, their positive effect appear to be negligible in the clinical trials. Therefore, prospective controlled studies are necessary to establish a dose-dependent molecular mechanism underlying the positive impact of antioxidants to overcome BPA toxicity for the possible clinical application.…”

“…BPA has a structural similarity with oestrogen; therefore, capable of binding with both ERα and ERβ [ 4 , 18 , 19 ]. As an ER modulator, BPA acting via genomic and non-genomic pathways ( Figure 1 ).…”