Juvenile sea bass biotransformation, genotoxic and endocrine responses to β-naphthoflavone, 4-nonylphenol and 17β-estradiol individual and combined exposures

Abstract

Juvenile sea bass, Dicentrarchus labrax L., were exposed during 2, 4, 8, and 24 h to 0.9 μM β-naphthoflavone (BNF), 131 nM 17β-estradiol (E 2), 4.05 μM 4-nonylphenol (NP), as well as to BNF combined either to E 2 or NP (maintaining the previous concentrations). Liver cytochrome P450 content (P450), ethoxyresorufin- O-deethylase (EROD), and glutathione S-transferase (GST) activities were measured in order to evaluate biotransformation responses. Genotoxicity was assessed as erythrocytic nuclear abnormalities (ENA) frequency. The effects on endocrine function were evaluated as plasma cortisol and glucose. Cortisol was not affected by xeno/estrogens tested, either in single exposure or mixed with BNF. Nevertheless, the intermediary metabolism was affected since glucose concentration increased after 4 h exposure to E 2, and after all BNF + NP exposure lengths. Moreover, a synergism between BNF and NP was thoroughly demonstrated, whereas a sporadic antagonistic interaction was found at 4 h BNF + E 2 exposure. Liver EROD and GST activities were not significantly altered by single E 2 or NP exposure. However, both compounds were able to induce EROD activity in the presence of BNF. NP single exposure was able to significantly increase liver P450 content, while its mixture with BNF displayed an antagonistic interference. Considering the xeno/estrogens single exposures, only NP induced an ENA increase; however, both mixtures (BNF + E 2 and BNF + NP) displayed genotoxic effects. Fish responses to mixtures of xenobiotics are complex and the type of interaction (synergism/potentiation or antagonism) in a particular mixture can vary with the evaluated biological response.