BDE-209 caused gut toxicity through modulating the intestinal barrier, oxidative stress, autophagy, inflammation, and apoptosis in mice

Decabromodiphenyl ether (BDE-209), a congener of polybrominated diphenyl ethers (PBDEs), is used as a flame retardant and accounts for over 82% of total PBDE usage. BDE-209 has been found to be persistent in indoor and outdoor environments and has adverse health effects on humans. This study aimed to investigate the effects of BDE-209 on mouse intestinal tissues and reveal the underlying toxicological mechanisms. In this study, C57BL/ 6J male mice were administered BDE-209 intragastrically (200 mg/kg bodyweight) once a day for 4 weeks, after which intestinal tissues, blood samples, and fecal samples were collected for analysis. The results showed that BDE-209 exposure significantly decreased body weight (P < 0.01) and promoted intestinal oxidative stress, apoptosis, autophagy, and inflammation. Additionally, BDE-209 reduced the intestinal mucus barrier and increased gut permeability. Importantly, BDE-209 decreased the levels of intestinal short-chain fatty acids (SCFAs), including acetic acid (P < 0.05) and butyric acid (P < 0.01), which protect gut health. Mechanistically, BDE-209 triggered apoptosis by damaging mitochondrial function, increasing both the release of mitochondrial cytochrome c (Cyt c) into the cytosol and the Bax/Bcl-2 ratio, as well as inducing activation of caspase-3, caspase-9, and PARP. Moreover, BDE-209 exposure induced intestinal inflammation via the TLR4/MyD88/NF kappa B signaling pathway and promoted intestinal autophagy by upregulating Beclin 1, leading to the accumulation of LC3-I to LC3-II. Therapeutically, N-acetyl-L-cysteine (NAC) attenuated the effects of BDE-209 on gut toxicity, including intestinal permeability, apoptosis, and inflammation through the oxidative stress pathway. Overall, we suggest that BDE-209 causes gut toxicity by modulating the intestinal barrier, permeability, oxidative stress, autophagy, apoptosis, and inflammation, and BDE-209 exposure could be partly reversed by antioxidant NAC supplementation. Our findings provide new insights into the intestinal response to BDE-209 exposure. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study found that exposure to BDE-209 resulted in reduced body weight, intestinal oxidative stress, apoptosis, autophagy, and inflammation in mice, as well as decreased intestinal mucus barrier and increased gut permeability. Furthermore, BDE-209 lowered levels of intestinal short-chain fatty acids. NAC attenuated the effects of BDE-209 on gut toxicity through the oxidative stress pathway.