Effects of dietary tert-butylhydroquinone on domoic acid metabolism and transcription of detoxification-related liver genes in red sea bream Pagrus major

Domoic acid (DA) is a neuroexcitatory amino acid that is produced by Pseudo-nitzschia during harmful algal blooms (HAB). Accumulation of DA can be transferred through food chain and cause neuronal damage in marine animal and in human. Like other algal toxins, DA was suggested to increase the oxidative stress and increase the detoxification-related gene expression in fish. The widely used food antioxidant, tert-butylhydroquinone (tBHQ), was known to induce a wide range of antioxidative potentials such as elevation of the glutathione levels and glutathione S-transferases (GSTs), via the activation of antioxidant response elements (AREs). In this study, the influences of dietary tBHQ on domoic acid (DA) metabolism and detoxification-related gene transcription were investigated both in vivo and in vitro. Oral administration of tBHQ resulted in significant decreases of DA accumulation of liver tissues in which red sea bream were fed with a single dose of 10 mg DA and 100 mg tBHQ per kg body weight per fish. Real-time PCR further revealed that the mRNA levels of AHR/ARNT/CYP1A1/IGSTA1/GSTR were up-regulated in the above liver tissues at 72 h post tBHQ treatment. In consistence, tBHQ exposure also resulted in increased mRNA transcription of GSTA1, GSTA2 and GSTR in cultured red sea bream hepatocytes. Collectively, our findings in this research suggested that the dietary intake of tBHQ accelerated DA metabolism in fish, through mechanisms involving altered transcription of detoxification-related liver genes.