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

Abstract

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.