Non-steroidal anti-inflammatory drugs caused an outbreak of
inflammation and oxidative stress with changes in the gut
microbiota in rainbow trout (Onconhytichus mykiss)

J 2022

Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss)

HODKOVICOVA, N., A. HOLLEROVA, J. BLAHOVA, P. MIKULA, M. CRHANOVA et. al.

Basic information

Original name

Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss)

Authors

HODKOVICOVA, N. (guarantor), A. HOLLEROVA, J. BLAHOVA, P. MIKULA, M. CRHANOVA, D. KARASOVA, Aleš FRANC (203 Czech Republic, belonging to the institution), Sylvie PAVLOKOVÁ (203 Czech Republic, belonging to the institution), J. MARES, E. POSTULKOVA, F. TICHY, P. MARSALEK, J. LANIKOVA, M. FALDYNA and Z. SVOBODOVA

Edition

Science of the Total Environment, Amsterdam, Elsevier, 2022, 0048-9697

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.800

RIV identification code

RIV/00216224:14160/22:00127329

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.1016/j.scitotenv.2022.157921

UT WoS

000880210200013

Keywords in English

Ibuprofen; Diclofenac; Microbiome; Gene expression; Histology; Toxicity

Abstract

V originále

One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs - diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100x higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.

Citovat

HODKOVICOVA, N., A. HOLLEROVA, J. BLAHOVA, P. MIKULA, M. CRHANOVA, D. KARASOVA, Aleš FRANC, Sylvie PAVLOKOVÁ, J. MARES, E. POSTULKOVA, F. TICHY, P. MARSALEK, J. LANIKOVA, M. FALDYNA and Z. SVOBODOVA. Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss). Science of the Total Environment. Amsterdam: Elsevier, 2022, vol. 849, November, p. 1-16. ISSN 0048-9697. Available from: https://dx.doi.org/10.1016/j.scitotenv.2022.157921.

@article{2236212,
   author = {Hodkovicova, N. and Hollerova, A. and Blahova, J. and Mikula, P. and Crhanova, M. and Karasova, D. and Franc, Aleš and Pavloková, Sylvie and Mares, J. and Postulkova, E. and Tichy, F. and Marsalek, P. and Lanikova, J. and Faldyna, M. and Svobodova, Z.},
   article_location = {Amsterdam},
   article_number = {November},
   doi = {http://dx.doi.org/10.1016/j.scitotenv.2022.157921},
   keywords = {Ibuprofen; Diclofenac; Microbiome; Gene expression; Histology; Toxicity},
   language = {eng},
   issn = {0048-9697},
   journal = {Science of the Total Environment},
   title = {Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss)},
   url = {https://www.sciencedirect.com/science/article/pii/S0048969722050203},
   volume = {849},
   year = {2022}
}

TY  - JOUR
ID  - 2236212
AU  - Hodkovicova, N. - Hollerova, A. - Blahova, J. - Mikula, P. - Crhanova, M. - Karasova, D. - Franc, Aleš - Pavloková, Sylvie - Mares, J. - Postulkova, E. - Tichy, F. - Marsalek, P. - Lanikova, J. - Faldyna, M. - Svobodova, Z.
PY  - 2022
TI  - Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss)
JF  - Science of the Total Environment
VL  - 849
IS  - November
SP  - 1-16
EP  - 1-16
PB  - Elsevier
SN  - 00489697
KW  - Ibuprofen
KW  - Diclofenac
KW  - Microbiome
KW  - Gene expression
KW  - Histology
KW  - Toxicity
UR  - https://www.sciencedirect.com/science/article/pii/S0048969722050203
N2  - One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs - diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100x higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.
ER  -

HODKOVICOVA, N., A. HOLLEROVA, J. BLAHOVA, P. MIKULA, M. CRHANOVA, D. KARASOVA, Aleš FRANC, Sylvie PAVLOKOVÁ, J. MARES, E. POSTULKOVA, F. TICHY, P. MARSALEK, J. LANIKOVA, M. FALDYNA and Z. SVOBODOVA. Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Onconhytichus mykiss). \textit{Science of the Total Environment}. Amsterdam: Elsevier, 2022, vol.~849, November, p.~1-16. ISSN~0048-9697. Available from: https://dx.doi.org/10.1016/j.scitotenv.2022.157921.

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