Fatal attraction: Synthetic musk fragrances compromise multixenobiotic defense systems in mussels

We studied interactions of nitromusk compounds musk ketone and musk xylene and polycyclic musks Galaxolide™ (HHCB), Celestolide™ (ADBI), Tetralide™ (AHTN), and Traseolide™ (AITI) with multixenobiotic resistance (mxr) transporters in gill tissue of the marine mussel Mytilus californianus (Conrad, 1837). A competitive substrate transport test with rhodamine B was used to assay modulation of transport activity by musks. All tested musks inhibited the transport activity in the low μm range as indicated by increased accumulation of rhodamine B in the tissue. Compared to known substrates of mxr transporters, the effective concentration range was similar to quinidine and about 100 times higher than verapamil. Musk ketone and musk xylene also inhibited efflux of rhodamine B from gill tissue which was loaded with the dye and subsequently incubated with these compounds. Synthetic musk compounds are persistent environmental pollutants in aquatic environments with a high potential to bioaccumulate. As potent inhibitors of mxr transporters they may also play a role as chemosensitizers that enable toxic mxr substrates to accumulate in cells of aquatic organisms.