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

Abstract

h i g h l i g h t sPBDEs induced macrophage apoptosis. ROS levels were increased and GSH was depleted in PBDE-exposed macrophages. NAC could only partially attenuate the cytotoxicity of PBDEs. Both intrinsic and extrinsic apoptotic pathways were activated by PBDEs. Macrophage accessory cell function was inhibited by non-cytotoxic levels of PBDEs. a r t i c l e i n f o a b s t r a c tPolybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and are often detected in the environment, wildlife, and humans, presenting potential threats to ecosystem and human health. PBDEs can cause neurotoxicity, hepatotoxicity, and endocrine disruption. However, data on PBDE immunotoxicity are limited, and the toxicity mechanisms remain largely unknown. Both immune cell death and dysfunction can modulate the responses of the immune system. This study examined the toxic effects of 2,2 0 , 4,4 0 -tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) on the immune system by using peritoneal macrophages as the model. The macrophages were exposed to PBDEs, and cell death was determined through flow cytometry and immunochemical blot. The results showed that after 24 h of exposure, BDE-47 (>5 lM) and BDE-209 (>20 lM) induced cell apoptosis, increased intracellular reactive oxygen species (ROS) formation and depleted glutathione. BDE-47 was more potent than BDE-209; the cytotoxic concentrations for BDE-47 and BDE-209 were determined to be 5 lM and 20 lM, respectively, during 24 h of exposure. However, pretreatment with N-acetyl-L-cysteine (ROS scavenger) partially reversed the cytotoxic effects. Further gene expression analyses on Caspase-3,-8,-9, TNFR1, and Bax revealed that both intrinsic and extrinsic apoptotic pathways were activated. More importantly, non-cytotoxic concentrations BDE-47 (<2 lM) and BDE-209 (<10 lM) could impair macrophage accessory cell function in a concentration-dependent manner, but no effects were observed on phagocytic responses. These revealed effects of PBDEs on macrophages may shed light on the toxicity mechanisms of PBDEs and suggest the necessity of evaluating cellular functionality during the risk assessment of PBDE immunotoxicity.

The reproductive toxicity on the rotifer Brachionus plicatilis induced by BDE-47 and studies on the effective mechanism based on antioxidant defense system changes

“…The enhanced production of ROS can destroy the enzymatic activities that may be caused by decreased levels of glutathione (GSH) (Elumalai et al, 2007). This result is in agreement with previous studies (Livingstone et al, 1990;Stephensen et al, 2002;Lv et al, 2015). GR can catalyze GSSG to GSH to maintain the reduction potential (Gutteridge and .…”

“…One mechanism of injury involves ROS generation and reactions (He et al, 2008;Frouin et al, 2010;Yan et al, 2011). After exposure to PBDEs, the ROS contents were enhanced, and oxidative stress occurs (Livingstone, 1991;Stohs and Bagchi, 1995;Barata et al, 2005;Lv et al, 2015). The antioxidant defense system plays a critical role in protecting organisms from PBDEs-caused stress.…”

“…Studies conducted in recent years have focused on the possible mechanism of toxicity induced by PBDEs and the physiological responses to PBDEs, such as structural damage or disorder, and physiological activity changes have been reported (Lv et al, 2015). One mechanism of injury involves ROS generation and reactions (He et al, 2008;Frouin et al, 2010;Yan et al, 2011).…”

Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol‐Induced Acute Liver Injury

“…TNF- α can influence cell activity by activating caspase-8 and -10 [57]. Moreover, ROS activates caspase-3, -8, and -9, which are cysteine-dependent proteases that mediate cell death [58]. Caspase-9 directly influences caspase-3 activation, usually by interacting with caspase-8 [58].…”

In vitro cytotoxicity of decabrominated diphenyl ether (PBDE-209) to human red blood cells (hRBCs)

“…Previous studies have reported that the PBDEs are toxic to the liver activity (Zhou et al, 2002), thyroid and reproduction systems (Yu et al, 2015), nervous system (Costa et al, 2014) and immune system (Lv et al, 2015). Though some highly-toxic PBDEs have been banned in many countries, other PBDEs with relatively lower toxicity, such as BDE-209, are still largely produced and used in the world (Chen et al, 2012;Akortia et al, 2016).…”