The effects of the painkiller diclofenac and hypoxia on gene transcription and antioxidant system in the gills of three-spined stickleback

Lubiana, Pedro; Prokkola, Jenni M.; Nikinmaa, Mikko; Burmester, Thorsten; Kanerva, Mirella; Götting, Miriam

doi:10.1016/j.cbpc.2016.04.003

Cited by 10 publications

(8 citation statements)

References 56 publications

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“…MDA, as a typical oxidative product, its content significantly increased at 1.572×10 -3 μmolL −1 and 0.1572 μmolL −1 , corresponding to the decrease of GSH to some extent at 24 h. But with prolonged time, although MDA content became lower, but no significant differences compared to control at 168 h, suggesting weak oxidative damage to mosquito fish in the present investigation. Similar reports were recorded that DCF displayed relatively lower toxicity to fish species (Gröner et al, 2015;Lubiana et al, 2016). This could be related to the DCF exposure concentration and period, obvious damage of DCF to animals usually occurred at a very high concentration and more long-term exposure (Yang et al, 2011;Stepanova et al, 2013;Triebskorna., 2004;Ji et al, 2006) and this need further investigation for a more longer exposure.…”

Section: Enzyme Response Ofsupporting

confidence: 62%

Effects of diclofenac on the expression of Nrf2 and its downstream target genes in mosquito fish (Gambusia affinis)

Bao

Nie

et al. 2017

Aquatic Toxicology

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Diclofenac (DCF) is one of widely used non-steroidal anti-inflammatory drugs. Recently, this drug has been universally detected in aquatic environment. However, its potential adverse effects and oxidative stress toxic mechanisms on fish remain unclear. In the present study, we first cloned the crucial partial sequences of some key oxidative stress related genes, which include NF-E2-related factor 2 (Nrf2), NAD(P)H: quinoneoxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), Cu-Zn superoxide dismutase (SOD2), catalase (CAT), alpha-glutathione S-transferase (GSTA), and UDP-glucuronosyltransferases (UGT) in mosquito fish (Gambusia affinis). We also deduced amino acids of Nrf2 and then constructed the phylogenetic trees of Nrf2, NQO1 and GCLC, respectively. Results showed that a high identity percentage was founded between G. affinis and other bony fish species, such as Xiphophorus maculates and Poecilia reticulate. The transcriptional expression of these genes and partly related enzymes activities were then investigated under the included environmental relevant concentration DCF exposure (0μmolL, 1.572×10μmolL, 1.572×10μmolL, 0.1572μmolL and 1.572μmolL) for 24h and 168h. The expression of Nrf2 was inhibited at 24h but induced at 168h, exhibiting a significant time and/or dose-effect relationship under DCF exposure. Similar observation was found in its downstream target genes. However, Nrf2-mediated antioxidant enzymes activities displayed differently under the same concentration of DCF exposure for the same time. Under DCF exposure for 168h, the genes exhibited dramatic induction trend, but there were no significant changes in enzyme activities and MDA content. Overall, mRNA responses were more sensitive than enzyme changes in mosquito fish under DCF exposure.

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Section: Enzyme Response Ofsupporting

confidence: 62%

Effects of diclofenac on the expression of Nrf2 and its downstream target genes in mosquito fish (Gambusia affinis)

Bao

Nie

et al. 2017

Aquatic Toxicology

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“…In one such study on the three-spined stickleback (Gasterosteus aculeatus), exposure to diclofenac under hypoxic conditions (2.0 ± 0.2 mg l −1 dissolved oxygen) has been shown to result in the upregulation in the liver of cytochrome P4501A (CYP1A) activity, which mediates chemical biotransformation (Prokkola et al, 2015). However, by contrast, downregulation of cyp1a1 (and hsp90) occurs in the gills of G. aculeatus (Lubiana et al, 2016) under the same exposure conditions. Thus, oxygen availability can potentially affect toxicity via both chemical uptake and responses in the enzyme detoxification system and this may vary among different tissues and result in differences in tissue sensitivities to the affects of hypoxia (Prokkola et al, 2015;Lubiana et al, 2016).…”

Section: ) Oxygenmentioning

confidence: 99%

Global variation in freshwater physico‐chemistry and its influence on chemical toxicity in aquatic wildlife

et al. 2021

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Chemical pollution is one of the major threats to global freshwater biodiversity and will be exacerbated through changes in temperature and rainfall patterns, acid–base chemistry, and reduced freshwater availability due to climate change. In this review we show how physico‐chemical features of natural fresh waters, including pH, temperature, oxygen, carbon dioxide, divalent cations, anions, carbonate alkalinity, salinity and dissolved organic matter, can affect the environmental risk to aquatic wildlife of pollutant chemicals. We evidence how these features of freshwater physico‐chemistry directly and/or indirectly affect the solubility, speciation, bioavailability and uptake of chemicals [including via alterations in the trans‐epithelial electric potential (TEP) across the gills or skin] as well as the internal physiology/biochemistry of the organisms, and hence ultimately toxicity. We also show how toxicity can vary with species and ontogeny. We use a new database of global freshwater chemistry (GLORICH) to demonstrate the huge variability (often >1000‐fold) for these physico‐chemical variables in natural fresh waters, and hence their importance to ecotoxicology. We emphasise that a better understanding of chemical toxicity and more accurate environmental risk assessment requires greater consideration of the natural water physico‐chemistry in which the organisms we seek to protect live.

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“…In the present case, these were reflected by a reduction in CAT activity in the trained animals receiving diclofenac. It has been previously demonstrated that diclofenac treatment suppressed CAT activity in gills but increased GPx activity, probably as a compensatory mechanism to reduce the accumulation of H2O2 [ 47 ]. The present study also assessed the effect of diclofenac on the glutathione redox cycle in rat model.…”

Section: Discussionmentioning

confidence: 99%

Diclofenac Administration after Physical Training Blunts Adaptations of Peripheral Systems and Leads to Losses in Exercise Performance: In Vivo and In Silico Analyses

et al. 2021

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Recovery in athletes is hampered by soreness and fatigue. Consequently, nonsteroidal anti-inflammatory drugs are used as an effective strategy to maintain high performance. However, impact of these drugs on adaptations induced by training remains unknown. This study assessed the effects of diclofenac administration (10 mg/kg/day) on rats subjected to an exhaustive test, after six weeks of swimming training. Over the course of 10 days, three repeated swimming bouts were performed, and diclofenac or saline were administered once a day. Trained animals exhibited higher muscle citrate synthase and lower plasma creatinine kinase activities as compared to sedentary animals, wherein diclofenac had no impact. Training increased time to exhaustion, however, diclofenac blunted this effect. It also impaired the increase in plasma and liver interleukin-6 levels. The trained group exhibited augmented catalase, glutathione peroxidase, and glutathione reductase activities, and a higher ratio of reduced-to-oxidized glutathione in the liver. However, diclofenac treatment blunted all these effects. Systems biology analysis revealed a close relationship between diclofenac and liver catalase. These results confirmed that regular exercise induces inflammation and oxidative stress, which are crucial for tissue adaptations. Altogether, diclofenac treatment might be helpful in preventing pain and inflammation, but its use severely affects performance and tissue adaptation.

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The effects of the painkiller diclofenac and hypoxia on gene transcription and antioxidant system in the gills of three-spined stickleback

Cited by 10 publications

References 56 publications

Effects of diclofenac on the expression of Nrf2 and its downstream target genes in mosquito fish (Gambusia affinis)

Effects of diclofenac on the expression of Nrf2 and its downstream target genes in mosquito fish (Gambusia affinis)

Global variation in freshwater physico‐chemistry and its influence on chemical toxicity in aquatic wildlife

Diclofenac Administration after Physical Training Blunts Adaptations of Peripheral Systems and Leads to Losses in Exercise Performance: In Vivo and In Silico Analyses

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