Decabromodiphenyl ether induces ROS-mediated intestinal toxicity through the Keap1-Nrf2 pathway

Area of Science:

• Environmental Toxicology
• Gastroenterology
• Cellular Biology

Background:

• Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants.
• PBDEs are known to cause various toxic effects, including hepatic, reproductive, neural, and thyroid toxicity.
• The intestinal toxicity of decabrominated diphenyl ether (PBDE-209) remains less understood.

Purpose of the Study:

• To investigate the in vivo and in vitro intestinal toxicity of decabrominated diphenyl ether (PBDE-209).
• To elucidate the potential toxicity mechanisms of PBDE-209 in the intestine.
• To assess the impact of PBDE-209 on oxidative stress and gene expression in intestinal cells.

Main Methods:

• In vivo study: Mice were exposed to PBDE-209 to assess intestinal oxidative stress markers.
• In vitro study: Caco-2 cells were treated with varying concentrations of PBDE-209 (1, 5, 25 μmol/L) for 24 and 48 hours.
• Assays included cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and mRNA expression analysis (Nrf2, FAS, CYP1A1) via real-time PCR.

Main Results:

• PBDE-209 significantly injured the mouse colon, increasing malondialdehyde (MDA) levels and altering antioxidant enzyme activities.
• In Caco-2 cells, PBDE-209 inhibited proliferation, induced cytotoxicity, and caused oxidative stress evidenced by increased ROS and altered MMP.
• PBDE-209 suppressed the mRNA expression of the antioxidant factor Nrf2 while increasing FAS and CYP1A1 mRNA levels.

Conclusions:

• Decabrominated diphenyl ether (PBDE-209) exerts significant intestinal toxicity both in vivo and in vitro.
• PBDE-209 induces oxidative stress in intestinal cells by disrupting ROS balance and mitochondrial function.
• The compound inhibits crucial antioxidative defense gene expression, contributing to its intestinal toxicity.