Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro

Abstract

Brominated diphenyl ether (BDE)-47 is a prevalent flame retardant chemical found in human tissues and is linked to adverse pregnancy outcomes in humans. Because dysregulation of the prostaglandin pathway is implicated in adverse pregnancy outcomes, the present study investigates BDE-47 induction of prostaglandin synthesis in a human extravillous trophoblast cell line, HTR-8/SVneo, examining the hypothesis that BDE-47 increases generation of reactive oxygen species (ROS) to stimulate the prostaglandin response. Treatment with 20 μM BDE-47 significantly increased mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) at 4, 12 and 24 h, and 24-h treatment significantly increased cyclooxygenase (COX)-2 cellular protein expression and prostaglandin E2 (PGE2) concentration in culture medium. The BDE-47-stimulated PGE2 release was inhibited by the COX inhibitors indomethacin and NS398, implicating COX activity. Exposure to 20 μM BDE-47 significantly increased ROS generation as measured by carboxydichlorofluorescein fluorescence, and this response was blocked by cotreatment with the peroxyl radical scavenger (±)-α-tocopherol. (±)-α-Tocopherol cotreatment suppressed BDE-47-stimulated increases of PGE2 release without significant effects on COX-2 mRNA and protein expression, implicating a role for ROS in post-translational regulation of COX activity. Because prostaglandins regulate trophoblast functions necessary for placentation and pregnancy, further investigation is warranted of BDE-47 impacts on trophoblast responses.

Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems

“…2014 ), bisphenols ( Kim et al. 2010 ), and brominated flame retardants ( Park and Loch-Caruso 2015 ) have all been shown to impact production in reproductive tissues.…”

Troxerutin Protects Kidney Tissue against BDE‐47‐Induced Inflammatory Damage through CXCR4‐TXNIP/NLRP3 Signaling

“…Substantial research suggested that the PBDE toxicity was strongly associated with PBDE-induced oxidative stress and inflammatory reactions. Interestingly, dietary sources of beneficial antioxidants such as flavonoids, α -tocopherol, and omega-3 polyunsaturated fatty acids could protect tissue cells against the toxicity of PBDEs, involved in mitochondrial electron transport system dysfunction, DNA fragmentation, and endoplasmic reticulum stress via blocking the generation of ROS [ 7 , 30 , 31 ]. Troxerutin, a natural flavonoid, possesses the efficacy of antioxidation and anti-inflammation.…”

“…Excessive ROS leads to the occurrence and development of inflammatory response [ 7 ]. As a result, BDE-47 augments the nuclear translocation of NF- κ B p65 in the liver, promotes the release of IL-6 and IL-8 [ 10 ], and increases the activity of COX-2 in human extravillous trophoblast cell line [ 31 ]. Our results also showed that BDE-47 induced ROS accumulation and TXNIP expression and then activated NLRP3 inflammasome and promoted mature IL-1 β secretion; in turn, triggered the translocation of NF- κ B p65 from the cytoplasm into the nuclear of kidney cells in the mice, advanced the expression of downstream inflammatory factors such as iNOS and COX-2, and ultimately enhanced urine protein production.…”

Troxerutin Reduces Kidney Damage against BDE‐47‐Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity

“…Increasing data reveal that BDE-47 induces oxidative stress and in turn mediates DNA damage, mitochondrial dysfunction, and endoplasmic reticulum stress [ 16 , 36 , 37 ]. Recently, antioxidants have been demonstrated to eliminate oxidative stress by scavenging ROS induced by BDE-47 in vitro [ 13 , 14 , 38 ]. Interestingly, we find that troxerutin could effectively reduce oxidative stress-mediated NAD + depletion and ameliorate liver inflammation injury.…”

“…Further studies show that natural products α -tocopherol, omega-3 polyunsaturated fatty acids, and troxerutin may be efficient candidate compounds against the damage induced by BDE-47 [ 13 – 16 ]. Troxerutin is a derivative of naturally occurring bioflavonoid rutin and enriched in fruits, vegetables, tea, coffee, and cereals.…”