Novel organ-specific effects of Ketoprofen and its enantiomer, dexketoprofen on toxicological response transcripts and their functional products in salmon

Mennillo, Elvira; Pretti, Carlo; Cappelli, Francesca; Luci, Giacomo; Intorre, Luigi; Meucci, Valentina; Arukwe, Augustine

doi:10.1016/J.AQUATOX.2020.105677

Title

Novel organ-specific effects of Ketoprofen and its enantiomer, dexketoprofen on toxicological response transcripts and their functional products in salmon

Author

Mennillo, Elvira

Pretti, Carlo

Cappelli, Francesca

Luci, Giacomo

Intorre, Luigi

Meucci, Valentina

Arukwe, Augustine

Abstract

Racemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are widely used non-steroidal antiinflammatory drugs (NSAIDs), and commonly detected in the aquatic environment. The present study has evaluated the toxicological effects of RS-KP and S(+)-KP on biotransformation and oxidative stress responses in gills and liver of Atlantic salmon. Fish were exposed for 10 days using different concentrations of RS-KP (1, 10 and 100 mu g/L) and S(+)-KP (0.5, 5 and 50 mu g/L). Biotransformation and oxidative stress responses were analysed at both transcript and functional levels. In the gills, significant inhibitory effect at transcriptional and enzymatic levels were observed for biotransformation and oxidative stress responses. On the contrary, biotransformation responses were significantly increased at transcriptional and translational levels in the liver, while the associated enzymatic activities did not parallel this trend and were inhibited and further demonstrated by principal component analysis (PCA). Our findings showed that both compounds produced comparable toxicological effects, by producing organ-specific effect differences. RS-KP and S(+)-KP did not bioaccumulate in fish muscle, either due to rapid metabolism or excretion as a result of their hydrophobic properties. Interestingly, the inhibitory effects observed in the gills suggest that these drugs may not undergo first pass metabolism, that might result to downstream differences in toxicological outcomes.

Language

English

Source (journal)

Aquatic toxicology. - Amsterdam

Publication

Amsterdam : 2020

ISSN

0166-445X

DOI

10.1016/J.AQUATOX.2020.105677

Volume/pages

229 (2020) , 10 p.