Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Decabromodiphenyl ethane (DBDPE),
a novel brominated flame retardant,
is becoming increasingly prevalent in environmental and biota samples.
While DBDPE has been shown to cause various biological adverse effects,
the molecular mechanism behind these effects is still unclear. In
this research, zebrafish embryos were exposed to DBDPE (50–400
μg/L) until 120 h post fertilization (hpf). The results confirmed
the neurotoxicity by increased average swimming speed, interfered
neurotransmitter contents, and transcription of neurodevelopment-related
genes in zebrafish larvae. Metabolomics analysis revealed changes
of metabolites primarily involved in glycolipid metabolism, oxidative
phosphorylation, and oxidative stress, which were validated through
the alterations of multiple biomarkers at various levels. We further
evaluated the mitochondrial performance upon DBDPE exposure and found
inhibited mitochondrial oxidative respiration accompanied by decreased
mitochondrial respiratory chain complex activities, mitochondrial
membrane potential, and ATP contents. However, addition of nicotinamide
riboside could effectively restore DBDPE-induced mitochondrial impairments
and resultant neurotoxicity, oxidative stress as well as glycolipid
metabolism in zebrafish larvae. Taken together, our data suggest that
mitochondrial dysfunction was involved in DBDPE-induced toxicity,
providing novel insight into the toxic mechanisms of DBDPE as well
as other emerging pollutants.