Diclofenac, ibuprofen and mixture thereof caused oxidative stress and increase of hsp70 in rainbow trout

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F22%3AN0000097" target="_blank" >RIV/00027162:_____/22:N0000097 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Diclofenac, ibuprofen and mixture thereof caused oxidative stress and increase of hsp70 in rainbow trout

Popis výsledku v původním jazyce

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequent and most common pharmaceuticals used in medicine due to their analgesic, antipyretic, and anti-inflammatory effects. Their use on daily basis resulted in NSAIDs have a leading position among the pharmaceutical contaminants present in the aquatic environment. Even so, their complex mechanism of toxicity for fish is not fully understood. We selected rainbow trout (Oncorhynchus mykiss) as an ideal model to examine the impact of two NSAIDs – diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity via dietary exposure of environmentally relevant concentrations (2 µg kg-1) of these drugs together with exposure doses of 100× higher (200 µg kg-1), including their mixture (combination of 2 µg kg-1 DCF and 2 µg kg-1 IBP). Here, we present the results of oxidative stress markers and gene expression. The kidneys, liver and gills were discovered to be the most severely affected tissues in our experiment and in all of them, the outbreak of reactive oxygen species (ROS) was observed. In posterior kidney, the environmentally relevant DCF concentration caused an increase in the catalase (CAT) activity – an enzyme which major function is to eliminate hydrogen peroxide as one of the ROS representatives. In liver, marker of lipoperoxidation (TBARS), increased in DCF2 and IBP200, as well as in DCF2+IBP2 combination. Regards gills, we confirmed the decreased glutathione peroxidase (IBP2, IBP200 and DCF2+IBP2) and CAT activity (DCF200). In general, ROS can oxidise cellular macromolecules, i.e. lipids, proteins and DNA, and provoke cell death. The heat shock protein 70 (hsp70) is a commonly used marker for assessing the impact of environmental pollutants and its mRNA levels are known to increase in response to various types of stress. Hsp70 is also an important factor in protein function, maintaining cell homeostasis, and affecting cytokine production. Regards hsp70 expression, the environmental concentration of IBP caused an increase in the anterior kidney and liver. In gills, the hsp70 expression increased in both tested concentration of IBP. In conclusion, due to changes in activity of antioxidant enzymes, we assume that the toxicity of NSAIDs in rainbow trout manifests itself mainly through their effect on the function of mitochondria. Damage of mitochondria can lead to increased ROS and cell death; consequently, the ROS increase can provoke a proteotoxicity that reflected by hsp70 increase in kidney, liver and gills. We kindly invite you to take a look at our poster and our study results (Hodkovicova et al., 2022), where the detected changes are presented in a comprehensive overview.

Název v anglickém jazyce

Diclofenac, ibuprofen and mixture thereof caused oxidative stress and increase of hsp70 in rainbow trout

Popis výsledku anglicky

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequent and most common pharmaceuticals used in medicine due to their analgesic, antipyretic, and anti-inflammatory effects. Their use on daily basis resulted in NSAIDs have a leading position among the pharmaceutical contaminants present in the aquatic environment. Even so, their complex mechanism of toxicity for fish is not fully understood. We selected rainbow trout (Oncorhynchus mykiss) as an ideal model to examine the impact of two NSAIDs – diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity via dietary exposure of environmentally relevant concentrations (2 µg kg-1) of these drugs together with exposure doses of 100× higher (200 µg kg-1), including their mixture (combination of 2 µg kg-1 DCF and 2 µg kg-1 IBP). Here, we present the results of oxidative stress markers and gene expression. The kidneys, liver and gills were discovered to be the most severely affected tissues in our experiment and in all of them, the outbreak of reactive oxygen species (ROS) was observed. In posterior kidney, the environmentally relevant DCF concentration caused an increase in the catalase (CAT) activity – an enzyme which major function is to eliminate hydrogen peroxide as one of the ROS representatives. In liver, marker of lipoperoxidation (TBARS), increased in DCF2 and IBP200, as well as in DCF2+IBP2 combination. Regards gills, we confirmed the decreased glutathione peroxidase (IBP2, IBP200 and DCF2+IBP2) and CAT activity (DCF200). In general, ROS can oxidise cellular macromolecules, i.e. lipids, proteins and DNA, and provoke cell death. The heat shock protein 70 (hsp70) is a commonly used marker for assessing the impact of environmental pollutants and its mRNA levels are known to increase in response to various types of stress. Hsp70 is also an important factor in protein function, maintaining cell homeostasis, and affecting cytokine production. Regards hsp70 expression, the environmental concentration of IBP caused an increase in the anterior kidney and liver. In gills, the hsp70 expression increased in both tested concentration of IBP. In conclusion, due to changes in activity of antioxidant enzymes, we assume that the toxicity of NSAIDs in rainbow trout manifests itself mainly through their effect on the function of mitochondria. Damage of mitochondria can lead to increased ROS and cell death; consequently, the ROS increase can provoke a proteotoxicity that reflected by hsp70 increase in kidney, liver and gills. We kindly invite you to take a look at our poster and our study results (Hodkovicova et al., 2022), where the detected changes are presented in a comprehensive overview.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

40301 - Veterinary science

Projekt

<a href="/cs/project/EF16_019%2F0000869" target="_blank" >EF16_019/0000869: Udržitelná produkce zdravých ryb v různých akvakulturních systémech - PROFISH</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů