Pharmacology-informed prediction of the risk posed to fish by mixtures of non-steroidal anti-inflammatory drugs (NSAIDs) in the environment

Marmon, Philip; Owen, Stewart F.; Margiotta-Casaluci, Luigi

doi:10.1016/j.envint.2020.106222

Cited by 26 publications

(18 citation statements)

References 96 publications

(63 reference statements)

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“…This is probably because ibuprofen is characterized by a high safety profile and very low toxicity incidence, and this is based on the fact that ibuprofen has short plasma half-life and does not form pathological metabolites (44). The mechanism of this NSAIDs hepatoxicity involves alteration of covalent protein by reactive metabolites (20,37), oxidative stress generation (41) and mitochondrial injury (21). This supports recent reports that drugs like NSAIDs actually induce hepatoxicity which results in reduction of the liver tissue (29,2,40).…”

Section: Discussionsupporting

confidence: 82%

Histomorphological and biochemical alterations on the liver of Wistar rats following co-administration of NSAIDs (Piroxicam, Diclofenac and Ibuprofen)

Umoh¹,

Umanah²,

Obot³

et al. 2022

Anat. J. Afr.

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Non-steroidal anti-inflammatory drugs (NSAIDs) are an important therapeutic class of drugs widely used to suppress acute or chronic pains and inflammatory diseases such as in rheumatoid arthritis (RA), osteoarthritis (OS) etc. The aim of this study was to investigate the random combination and individual effect of COX-2 inhibitors (NSAIDs) on the liver. This study was conducted using a total of 40 adults Wistar rats. The rats were divided into eight groups of 5 rats each. Group one was the control group, group 2 was given piroxicam (0.29mg/kg) daily, group 3 was given ibuprofen (5.71mg/kg) daily, and group 4 received diclofenac (1.42mg/kg) daily. Group 5 received piroxicam (0.29mg/kg bodyweight) plus ibuprofen (0.58mg/kg), group 6 received piroxicam (0.29mg/kg) plus diclofenac (1.42mg/kg) and group 7 received ibuprofen (0.58mg/kg) plus diclofenac (1.42mg/kg) respectively daily. Group 8 was given Piroxicam (0.29mg/kg bodyweight) plus Ibuprofen (5.71mg/kg) plus diclofenac (1.42mg/kg) daily. Intervention was over a period of 3days. Animals were sacrificed after 24 hours and the liver tissues were excised, some were fixed in 10% neutral buffered formalin for histological studies while others were placed in normal saline for biochemical analysis. The results revealed that there was no significant statistical difference in total bilirubin, ALT and AST when compared to the control. This suggests that NSAIDs may have no significant effects on the liver for this regimen. Histological changes observed were congested portal vein, haemorrhagic bile ducts, distortion of portal triad and sinusoids, and degeneration of hepatocytes. In conclusion, NSAIDs may have harmful effect on the cytoarchitecture of the liver which can lead to liver damage especially when given in high doses and in combination, but however it had no effect on liver function.

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Section: Discussionsupporting

confidence: 82%

Histomorphological and biochemical alterations on the liver of Wistar rats following co-administration of NSAIDs (Piroxicam, Diclofenac and Ibuprofen)

Umoh¹,

Umanah²,

Obot³

et al. 2022

Anat. J. Afr.

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“…Strategies to manage OA are mainly the conventional medicines used, which have side effects such as liver damage and gastrointestinal discomfort. 27 Therefore, these main symptoms and long-term management of OA can cause great distress and inconvenience to the patient. 28 However, the mechanism of OA is still not fully understood, studies suggest that inflammation and autophagy are closely related to the progression of OA.…”

Section: Discussionmentioning

confidence: 99%

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

Lu¹,

Wei²,

Wang³

et al. 2023

iScience

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“…Appropriate methodology has been developed [ 49 ] to enable worthwhile, informative experiments to be designed and their data correctly analysed and interpreted. In addition, Marmon et al (2021) [ 50 ] demonstrated the high potential of using network pharmacology concepts integrated with pharmacokinetics considerations to predict the environmental risk posed by a complex mixture of pharmaceuticals (i.e., 25 NSAIDs). However, formidable obstacles still need to be overcome before it is possible to know whether the presence of complex mixtures of neuroactive substances representative of those present in the aquatic environment pose a significant risk to aquatic organisms.…”

Section: Discussionmentioning

confidence: 99%

“…This understanding will be critical to support the identification of a suitable set of new approach methodologies (NAMs) that could be deployed to predict the risk of chemical-induced behavioural alterations without the need to perform animal testing. In this context, the consideration of drug-specific comparative pharmacology, target conservation across species, the in vitro bioactivity profile, and comparative pharmacokinetics (PK) may provide valuable tools to address this challenge [ 15 , 50 ]. In the case of neuroactive pharmaceuticals, this effort can be facilitated by the (generally) advanced understanding of the PK and pharmacodynamic (PD) properties of these compounds in mammals.…”

Section: Discussionmentioning

confidence: 99%

Environmental Occurrence and Predicted Pharmacological Risk to Freshwater Fish of over 200 Neuroactive Pharmaceuticals in Widespread Use

Sumpter

Margiotta-Casaluci

2022

Toxics

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There is a growing concern that neuroactive chemicals released into the environment can perturb wildlife behaviour. Among these chemicals, pharmaceuticals such as antidepressants and anxiolytics have been receiving increasing attention, as they are specifically prescribed to modify behavioural responses. Many laboratory studies have demonstrated that some of these compounds can affect various aspects of the behaviour of a range of aquatic organisms; however, these investigations are focused on a very small set of neuroactive pharmaceuticals, and they often consider one compound at a time. In this study, to better understand the environmental and toxicological dimension of the problem, we considered all pharmaceuticals explicitly intended to modulate the central nervous system (CNS), and we hypothesised that these compounds have higher probability of perturbing animal behaviour. Based on this hypothesis, we used the classification of pharmaceuticals provided by the British National Formulary (based on their clinical applications) and identified 210 different CNS-acting pharmaceuticals prescribed in the UK to treat a variety of CNS-related conditions, including mental health and sleep disorders, dementia, epilepsy, nausea, and pain. The analysis of existing databases revealed that 84 of these compounds were already detected in surface waters worldwide. Using a biological read-across approach based on the extrapolation of clinical data, we predicted that the concentration of 32 of these neuroactive pharmaceuticals in surface waters in England may be high enough to elicit pharmacological effects in wild fish. The ecotoxicological effects of the vast majority of these compounds are currently uncharacterised. Overall, these results highlight the importance of addressing this environmental challenge from a mixture toxicology and systems perspective. The knowledge platform developed in the present study can guide future region-specific prioritisation efforts, inform the design of mixture studies, and foster interdisciplinary efforts aimed at identifying novel approaches to predict and interpret the ecological implications of chemical-induced behaviour disruption.

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Pharmacology-informed prediction of the risk posed to fish by mixtures of non-steroidal anti-inflammatory drugs (NSAIDs) in the environment

Cited by 26 publications

References 96 publications

Histomorphological and biochemical alterations on the liver of Wistar rats following co-administration of NSAIDs (Piroxicam, Diclofenac and Ibuprofen)

Histomorphological and biochemical alterations on the liver of Wistar rats following co-administration of NSAIDs (Piroxicam, Diclofenac and Ibuprofen)

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

Environmental Occurrence and Predicted Pharmacological Risk to Freshwater Fish of over 200 Neuroactive Pharmaceuticals in Widespread Use

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