Cytotoxic effects and oxidative stress response of six PBDE metabolites on human L02 cells

Abstract

In the present study, the cytotoxic effects and toxicological mechanism of six polybrominated diphenyl ethers (PBDEs) metabolites (3-OH-BDE47, 3-MeO-BDE47, 5-OH-BDE47, 5-MeO-BDE47, 6-OH-BDE85 and 6-MeO-BDE85) on L02 cells were explored by investigating the cell viability, apoptosis, lactic dehydrogenase (LDH) leakage, and oxidative stress response. The results showed that these metabolites could inhibit cell proliferation and induce apoptosis, among which 6-OH-BDE85 had the highest efficiency. LDH leakage test also showed that 6-OH-BDE85 had the strongest ability to cause LDH release. The reactive oxygen species (ROS) levels in 6-OH-BDE85- and 3-OH-BDE47-treated groups were significantly elevated in a dose-dependent manner. After treatment for 24 h, four BDE47 metabolites (3-OH-BDE47, 3-MeO-BDE47, 5-OH-BDE47, and 5-MeO-BDE47) induced an increase in superoxide dismutase (SOD) activity and decrease in glutathione (GSH) level, whereas 6-OH-BDE85 led to a decrease in both SOD activity and GSH level. These effects disappeared after continued culturing for another 24 h. In conclusion, these PBDE metabolites, especially 6-OH-BDE85, showed cytotoxicity on L02 cells, which was at least partially related to the oxidative stress level.

In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: Apoptosis and immune cell dysfunction

“…Recently, experimental data using animal models strongly suggested the occurrence of PBDE immunotoxicity, manifested as altered splenic lymphocyte populations, increased susceptibility to infections, and the release of pro-inflammatory cytokines (Zhong et al, 2011;Pellacani et al, 2012;Bondy et al, 2013). However, the data on PBDE immunotoxicity are still limited, and the mechanism(s) remains largely unclear.…”

“…The data showed that the reduction of GSH occurred in parallel with the over-production of ROS, in response to BDE-47 and BDE-209 exposure. In vitro, at various concentrations, PBDE-induced oxidative stress was also commonly found in many cell lines, including gonadal cells and germ cells (Jin et 2012), liver cells (Zhong et al, 2011), and immune cells (Yan et al, 2011), causing global gene disturbance and DNA damage. In vivo, oxidative stress was previously demonstrated as a mechanism of PBDE toxicity in earthworms (Eisenia fetida) (Xie et al, 2011) and CD-1 mice (Tseng et al, 2013).…”

A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity

“…PBDE-induced oxidative stress has also been observed in non-nervous tissue cell types, such as human fetal liver hematopoietic cells (Shao et al 2008), human hepatoma cells HepG2 (Hu et al 2007; 2009), Jurkat T cells (Yan et al 2011), and human umbilical vein endothelial cells (Kawashiro et al 2009). Certain hydroxylated PBDEs have also been shown to induce oxidative stress in human liver L02 cells (Zhong et al 2011). …”

Multiple biomarkers of the cytotoxicity induced by BDE-47 in human embryonic kidney cells

“…In addition, BDE-47 is one of five main PBDE congeners Some in vitro studies have revealed that BDE-47 could cause toxic effects, such as developmental neurotoxicity, hepatotoxicity, reproduction toxicity, immunotoxicity and endocrine disruption (Lema et al, 2008;Song et al, 2009;Kodavanti et al, 2010;An et al, 2011;Erratico et al, 2011;Zhong et al, 2011;Chen et al, 2012). Apoptosis is a form of self-regulated cell death and a major manifestation of cytotoxicity of contaminants (Kerr et al, 1972).…”

“…In traditional toxicological studies, one or several biomarkers are usually chosen to assess the cytotoxicity of BDE-47 such as apoptosis and ROS production to test for oxidative stress or specific expressed proteins and genes to test for certain toxicities (Crump et al, 2008;Zhong et al, 2011;Wang et al, 2012). However, a single biomarker only indicates a certain toxic effect, which usually lacks a global view on cytotoxicity of BED-47.…”