Preliminary results on the uptake and biochemical response to water-exposure of Tamiflu® (oseltamivir phosphate) in two marine bivalves

ABSTRACT

Tamiflu® (oseltamivir phosphate, OST) is an antiviral drug used for the pandemic treatment of avian influenza but few data are available regarding its toxicity. It should be noted that acute adverse responses are not likely to occur due to low environmental presence of this drug. Nonetheless, water concentration levels of this compound may reach the µg/L range under influenza episodes. Bivalves are reliable sentinels of chemical exposure due to their low metabolism; however, biotransformation of drugs does occur in these aquatic invertebrates. Two species of bivalves, namely mussels Mytilus galloprovincialis and clams Ruditapes philippinarum, were exposed for 48 h to 100 µg/L OST. Hemolymph from control and treated bivalves was withdrawn and the presence of OST and its metabolite oseltamivir carboxylate (OST-C) determined by LC-MS/MS. Gills and digestive gland were excised from control and exposed bivalves and carboxylesterase (CE) activities measured using different substrates. In addition, antioxidant defences and lipid peroxidation levels were determined. Higher metabolism of OST seemed to occur in mussels, since both OST and OST-C were found in hemolymph, whereas in clams only the parent compound was detected. In contrast, biomarker responses were more evident in exposed clams which indicate that this species may be considered as more sensitive to OST exposure. CE-related activities successfully reflected OST exposure, with substrates 1-naphthyl acetate (1NA) and 1-naphthyl butyrate (1NB) displaying the highest sensitivity in the two bivalve species. Data thus indicate the usefulness of CE-related activities as biomarkers for OST exposure in bivalves.

KEYWORDS:

• Bivalves
• antiviral drug
• oseltamivir carboxylate
• carboxylesterases
• oxidative stress

Acknowledgements

The Spanish Ministry of Economy and Competitivity (ref. CGL2016-76332-R Mineco/FEDER/UE). SCIEX for generously providing the loan instrument. Merck is acknowledged for the gift of LC columns.

Conflict of interest

The authors declare that they have no conflict of interest.

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Funding

This work was supported by the Spanish Ministry of Economy, Industry and Competitivity [ref CGL2016-76332-R MINECO/FEDER/UE].