Bisphenol A-induced apoptosis, oxidative stress and DNA damage in cultured rhesus monkey embryo renal epithelial Marc-145 cells

Highlights

• Bisphenol A induced rhesus monkey embryo renal epithelial Marc-145 cell apoptosis in vitro.

• Bisphenol A increased LDH activity, ROS- generation, and TBARS content.

• Bisphenol A decreased cell viability, SOD activity and GSH level.

• Bisphenol A induced oxidative stress and resulted in DNA damage of Marc-145 cells.

Abstract

Bisphenol A (BPA) is widely used in the production of epoxy resins and polycarbonate plastics. Under harsh situations, these plastics likely desorb BPA, which then can seep into the environment. Various concentrations of BPA have been detected in most biological fluid. However, there is paucity of information on the detrimental effects of BPA and its subsequent cellular events in chronic kidney disease (CKD). Hence, in this in vitro study, we aimed to investigate the effects of BPA on renal epithelial cell activation, apoptosis, and DNA damage. Rhesus monkey embryo renal epithelial Marc-145 cells were exposed to 0, 10⁻¹, 10⁻², 10⁻³, 10⁻⁴, 10⁻⁵, and 10⁻⁶ M of BPA. Alterations in intracellular apoptosis, oxidative stress, and DNA damage were evaluated. The results showed that BPA decreased cell viability, superoxide dismutase (SOD) activity and glutathione (GSH) level, with concomitant increases in apoptosis related indices, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation, thiobarbituric acid reactive substances (TBARS) content, and the rate of comet Marc-145 cells with a dose-dependent manner. The data indicated that increased oxidative stress, apoptosis and DNA damage in epithelial Marc-145 cells might play a pivotal role in the mechanism of BPA-induced nephrotoxicity.

Introduction

Bisphenol A (BPA) is considered to be an environmental endocrine disrupting chemical (Lan et al., 2017, Russo et al., 2018). It is widely used in the manufacture of epoxy resins and polycarbonate plastics, as a key building block, for production of various consumer products, such as beverage cans, household electronics, medical and dental devices, thermal paper, plastic baby bottles, water and food containers, as well as other kitchen appliances (Rosenfeld, 2015, Björnsdotter et al., 2017, Lan et al., 2017, Russo et al., 2018, Li et al., 2019). During harsh situations, like exposure to high temperature, alkaline or acidic conditions, hydrolysis of BPA will result in its release, brings about widespread human exposure to this chemical through contaminated food, water, as well as inhalation and skin contact (Kang et al., 2006, Lan et al., 2017, Shi et al., 2017).

BPA has been detected in human amniotic fluid, blood, breast milk, placenta, sweat, and urine (Shi et al., 2017, Yu et al., 2019). An increasing number of investigations have shown a correlation between BPA and animal health anomalies, such as alterations in the endogenous cannabinoid system (ECS) of the central nervous system and liver, decreased quality and quantity indices of sperm, neuroendocrine disruption, as well as other malignancies, like breast and prostate cancer, diabetes, heart disease, and obesity (Maqbool et al., 2016, Forner-Piquer et al., 2018, Rezg et al., 2014, Caporossi and Papaleo, 2017, Lan et al., 2017). Meanwhile, there is a good body of literature demonstrating early exposure to BPA is related to children’s depression, as well as problems in behavioral traits and learning development (Harley et al., 2013, Hong et al., 2013). On the other hand, some animal studies reveal that exposure to BPA is associated with anxiety- and depression-like behaviors, as well as cognitive impairments (Hajszan and Leranth, 2010, Xu et al., 2015). Xu et al., 2007, Xu et al., 2010 have reported that perinatal exposure to BPA considerably induced anomalies on the offspring learning and memory abilities in male mice. Also, it has been shown that exposure to BPA in different cell lines significantly changed the expression levels of many genes involved in PLSCR1, CAPRIN1, PROK2, ZBTB16, and CYP (Ribeiro-Varandas et al., 2016, Lan et al., 2017). However, a few studies to date have focused on the renal related pathways and BPA-induced toxicity.

Marc-145 cells are derived from rhesus monkey embryonic renal epithelial cell line and may be targeted by environmental uremic toxin induced by BPA (González-Parra et al., 2013). Physiologically, an intact kidney is essential to the stability of the internal environment and normal metabolism. Under pathological conditions, multiple molecules accumulate in individuals affected by chronic kidney disease (CKD), causing uremic symptoms and increasing mortality, including weakness, anorexia, vomiting, sleep disorders and neuropathy, as well as cardiovascular morbidity, and progressive loss of renal function. Therefore, urinary toxins clearance is accompanied by the improvement of clinical conditions (Goldfarb et al., 2007, Wikoff et al., 2009, González-Parra et al., 2013).

Huang et al. (2017) have reported that oxidative stress is a fundamental mechanism of BPA-induced toxicity. It has also been reported that BPA can induce oxidative stress in HepG2 cells through reducing SOD activity, increasing the level of ROS, and TBARS content (Li et al., 2017). ROS can also lead to DNA damage (Pfeifer et al., 2015). Among infertile men, BPA exposure may also cause potential damage to semen DNA integrity and sperm quality (Omran et al., 2018). The damaged DNA may also affect cell functionality, leading to carcinogenic potential and all sorts of chronic diseases (Schupp et al., 2016). However, data regarding the toxic effects of BPA exposure on kidney system are still lacking. The main aim of the present in vitro study was to investigate the effects of BPA on rhesus monkey embryo renal epithelial cell activation, apoptosis, and DNA damage, and to evaluate whether mechanisms of oxidative stress are involved in these detrimental effects.