The Interference of Nitro- and Polycyclic Musks with Endogenous and Xenobiotic Metabolizing Enzymes in Carp: An In Vitro Study

Abstract

Synthetic musks are widely used as perfuming agents in products, such as cosmetics, detergents, and soaps. The increased detection of these substances in the aquatic environment and their high bioconcentration potential raises concerns about potential effects on aquatic species. This work aimed at assessing the interactions of the most widely used musks: nitromusks (musk xylene, musk ketone) and polycyclic musks (celestolide, galaxolide, and tonalide) with fish enzymatic systems involved in both xenobiotic and endogenous metabolism. Therefore, CYP catalyzed pathways were investigated in carp liver microsomes (CYP1A, CYP3A), ovarian microsomes (CYP19) and testicular mitochondria (CYP17 and CYP11beta) using standard substrates. Phase II activities (UDP-glucuronosyltransferases and sulfotransferases) were determined in carp liver microsomes and cytosol, respectively. Polycyclic musks (galaxolide and tonalide) were stronger inhibitors of CYP3A- (IC(50): 68-74 microM), CYP17- (IC(50): 213-225 microM), CYP11beta- and CYP19-catalyzed activities than nitromusks, while the latter showed higher ability to interfere with CYP1A (IC(50): 35-37 microM). The sulfation of estradiol was also significantly inhibited by tonalide and galoxolide (IC(50): 140-294 microM). Overall, polycyclic musks showed the highest potential to interfere with those activities involved in the synthesis and metabolism of steroids while nitromusks mainly interfered with xenobiotic metabolism (CYP1A-catalyzed reactions). The obtained data suggest that CYP isoforms are potentially sensitive targets of synthetic musk substances in fish.