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Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac

Näslund, Johanna and Asker, Noomi and Fick, Jerker and Larsson, D. G. Joakim and Norrgren, Leif (2020). Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac. Aquatic Toxicology. 227 , 105583
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Abstract

The presence of diclofenac in the aquatic environment and the risks for aquatic wildlife, especially fish, have been raised in several studies. One way to manage risks without enforcing improved wastewater treatment would be to substitute diclofenac (when suitable from a clinical perspective) with another non-steroidal anti-inflammatory drug (NSAID) associated with less environmental risk. While there are many ecotoxicity-studies of different NSAIDs, they vary extensively in set-up, species studied, endpoints and reporting format, making direct comparisons difficult. We previously published a comprehensive study on the effects of diclofenac in the three-spined stickleback (Gasterosteus aculeatus). Our present aim was to generate relevant effect data for another NSAID (naproxen) using a very similar setup, which also allowed direct comparisons with diclofenac regarding hazards and risks. Sticklebacks were therefore exposed to naproxen in flow-through systems for 27 days. Triplicate aquaria with 20 fish per aquarium were used for each concentration (0, 18, 70, 299 or 1232 mu g/L). We investigated bioconcentration, hepatic gene expression, jaw lesions, kidney and liver histology. On day 21, mortalities in the highest exposure concentration group unexpectedly reached >= 25 % in all three replicate aquaria, leading us to terminate and sample that group the same day. On the last day (day 27), the mortality was also significantly increased in the second highest exposure concentration group. Increased renal hematopoietic hyperplasia was observed in fish exposed to 299 and 1232 mu g/L. This represents considerably higher concentrations than those expected in surface waters as a result of naproxen use. Such effects were observed already at 4.6 mu g/L in the experiment with diclofenac (lowest tested concentration). Similar to the responses to diclofenac, a concentration-dependent increase in both relative hepatic gene expression of c7 (complement component 7) and jaw lesions were observed, again at concentrations considerably higher than expected in surface waters. Naproxen bioconcentrated less than diclofenac, in line with the observed effect data. An analysis of recent sales data and reported concentrations in treated sewage effluent in Sweden suggest that despite higher dosages used for naproxen, a complete substitution would only be expected to double naproxen emissions. In summary, naproxen and diclofenac produce highly similar effects in fish but the environmental hazards and risks are clearly lower for naproxen. Hence, if there are concerns for environmental risks to fish with diclofenac, a substitution would be advisable when naproxen presents an adequate alternative from a clinical point-of-view.

Authors/Creators:Näslund, Johanna and Asker, Noomi and Fick, Jerker and Larsson, D. G. Joakim and Norrgren, Leif
Title:Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac
Year of publishing :2020
Volume:227
Article number:105583
Number of Pages:13
Publisher:ELSEVIER
ISSN:0166-445X
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 105 Earth and Related Environmental Sciences > Environmental Sciences (social aspects to be 507)
Keywords:Naproxen, Diclofenac, Fish, Histology, Kidney, Quantitative PCR
URN:NBN:urn:nbn:se:slu:epsilon-p-108384
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-108384
Additional ID:
Type of IDID
DOI10.1016/j.aquatox.2020.105583
Web of Science (WoS)000574866700013
ID Code:18070
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:04 Nov 2020 13:04
Metadata Last Modified:04 Nov 2020 13:11

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