Brominated flame retardant TBPH induced oxidative damage and reduced the expression of memory-related proteins in mice, with no discernable impairment of learning and memory.

ABSTRACT

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is one of the new brominated flame retardants with adverse neurobehavioral potential. These flame retardants are often added to household furnishings where children would come into contact with them. This study explores whether oral exposure to TBPH for 28 days would impair neurobehavioral function in mice and the role of curcumin (CUR) in this process. CUR is a natural antioxidant and is thought to be of use in the treatment of neurological toxicity due to its neuroprotective effects. Learning and memory of mice exposed to TBPH was investigated using the Morris water maze. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined to assess oxidative damage. Western blot was used to detect the expression of glucose-regulated protein 78-kDa (GRP78), PKR-like ER kinase (PERK), and C/EBP homologous protein (CHOP) in the hippocampus. End-point effects were evaluated through observing post-synaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB). Although TBPH exposure alone does not impair learning and memory, oxidative stress markers and endoplasmic reticulum stress-associated proteins were adversely affected in exposed mice. TBPH could significantly decrease the levels of BDNF, p-CREB, and PSD-95 in the hippocampus, and these TBPH-induced neurotoxic effects were attenuated by CUR. These findings provide further understanding of the neurotoxic effects of TBPH and the protective effect of CUR on TBPH exposure.