Brevetoxin: tissue distribution and effect on cytochrome P450 enzymes in fish

As part of our investigation of the metabolism of brevetoxin (PbTx) in fish, we initiated a two-part study to determine the toxin's tissue distribution and its ability to induce xenobiotic metabolizing enzymes. In the first study, gulf toadfish (Opsanus beta) were administered 14C-PbTx-3 orally in a fishmeal slurry and sacrificed 72 hr later. Radioactivity was greatest in the hepatobiliary system (40% of body burden), representing the key role this system plays in the detoxification and elimination of brevetoxin. Muscle tissue contained 27%, followed by gastrointestinal tract (25%). To investigate the effects of PbTx on xenobiotic metabolizing enzymes, immature redfish (Scianops ocellatus) were given two doses of brevetoxin (1.5 or 2.5 micrograms/100 g body weight) or cod liver oil in a fishmeal slurry by gavage. The activities of two hepatic P450 enzymes, ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD), as well as the cytosolic enzyme, glutathione S-transferase (GST), were measured. At the higher dose, PbTx significantly increased EROD activity. These results suggest that brevetoxin is capable of inducing an important xenobiotic metabolizing enzyme (EROD).