Effects of acetaminophen (paracetamol) in the embryonic development of zebrafish, <i>Danio rerio</i>

David, Arthur; Pancharatna, Katti

doi:10.1002/jat.1446

Cited by 65 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the effect of paracetamol seem to differ from the generic effect of common drugs on the pigmentation of fish. In fact, the here‐obtained data are similar to those obtained by David and Pancharatna (2009), who showed that environmentally relevant concentrations of paracetamol during the embryonic development of D. rerio , could result in changes namely, (lack) of pigmentation …”

Section: Discussionmentioning

confidence: 99%

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Nogueira

Pinto

Correia

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

For several years, the scientific community has been concerned about the presence of pharmaceuticals in the wild, since these compounds may have unpredictable deleterious effects on living organisms. Two examples of widely used pharmaceuticals that are present in the environment are paracetamol and ciprofloxacin. Despite their common presence in the aquatic environment due to their poor removal by sewage treatment plants, knowledge concerning their putative toxic effects is still scarce. This work aimed to characterize the effects of paracetamol (0.005, 0.025, 0.125, 0.625, and 3.125 mg/L) and ciprofloxacin (0.005, 0.013, 0.031, 0.078, 0.195, and 0.488 μg/L) in zebrafish embryos and larvae, exposed to environmentally relevant levels, close to the real concentrations of these pharmaceuticals in surface waters and effluents. The adopted toxic end points were developmental, a behavioral parameter (total swimming time), and a biomarker‐based approach (quantification of the activities of catalase, glutathione‐S‐transferase, cholinesterases, glutathione peroxidase, and lipid peroxidation levels) combined with epigenetic analysis (immunohistochemical detection of 5‐methylcytidine). Exposure to paracetamol had effects on all of the adopted toxic end points; however, ciprofloxacin only caused effects on behavioral tests and alterations in biomarkers. It is possible to ascertain the occurrence of oxidative stress following exposure to both drugs, which was more evident regarding paracetamol, an effect that may be related to the observed epigenetic modifications.

show abstract

Section: Discussionmentioning

confidence: 99%

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Nogueira

Pinto

Correia

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…While two of them, ethanol [25] and lindane [26], are widely considered to be neurotoxins at high dose, three are candidate neurotoxins: acetaminophen [27], [28], atenolol [29] and atrazine [30], [31], [32]. The last one, mefenamic acid, is considered to be neuroprotectant [33].…”

Section: Discussionmentioning

confidence: 99%

“…Acetaminophen has also been previously tested in zebrafish and its general effect on embryonic development, nephrotoxicity and hepatotoxicity have been reported [27], [40], [41] but its neurotoxicity has not been studied. Its direct neurotoxic action has been recently established by both in vitro and in vivo studies in rats and neuronal apoptosis has been observed at concentration of 1–2 mM (150–300 mg/L) [28] Apparently the zebrafish larvae are more sensitive to acetaminophen as significant embryonic developmental defects were observed at concentration of 10 mg/L while significant shortening of axon length occurred at concentration as low as 2 mg/L.…”

Section: Discussionmentioning

confidence: 99%

Fluorescent Transgenic Zebrafish Tg(nkx2.2a:mEGFP) Provides a Highly Sensitive Monitoring Tool for Neurotoxins

Zhang

Gong

2013

PLoS ONE

View full text Add to dashboard Cite

Previously a standard toxicological test termed as DarT (Danio rerio Teratogenic assay) using wild type zebrafish embryos has been established and it is widely applied in toxicological and chemical screenings. As an increasing number of fluorescent transgenic zebrafish lines with specific fluorescent protein expression specifically expressed in different organs and tissues, we envision that the fluorescent markers may provide more sensitive endpoints for monitoring chemical induced phenotypical changes. Here we employed Tg(nkx2.2a:mEGFP) transgenic zebrafish which have GFP expression in the central nervous system to investigate its potential for screening neurotoxic chemicals. Five potential neurotoxins (acetaminophen, atenolol, atrazine, ethanol and lindane) and one neuroprotectant (mefenamic acid) were tested. We found that the GFP-labeled ventral axons from trunk motoneurons, which were easily observed in live fry and measured for quantification, were a highly sensitive to all of the five neurotoxins and the length of axons was significantly reduced in fry which looked normal based on DarT endpoints at low concentrations of neurotoxins. Compared to the most sensitive endpoints of DarT, ventral axon marker could improve the detection limit of these neurotoxins by about 10 fold. In contrast, there was no improvement for detection of the mefenamic acid compared to all DarT endpoints. Thus, ventral axon lengths provide a convenient and measureable marker specifically for neurotoxins. Our study may open a new avenue to use other fluorescent transgenic zebrafish embryos/fry to develop sensitive and specific toxicological tests for different categories of chemicals.

show abstract

“…Other PAHs, such as benzo[a]pyrene and retene, are known to undergo hepatic metabolism [24], [25], [26], and exposure results in developmental malformations, including edemas and craniofacial malformations, in the developing zebrafish [27], [28], [29]. Certain pharmaceuticals, including acetaminophen and flutamide, are known to result in human hepatotoxicity [30], [31], [32], and can result in developmental toxicity in the zebrafish model [33].…”

Section: Introductionmentioning

confidence: 99%

Investigating the application of a nitroreductase-expressing transgenic zebrafish line for high-throughput toxicity testing

Chlebowski

Truong

et al. 2017

Toxicology Reports

View full text Add to dashboard Cite

Nitroreductase enzymes are responsible for the reduction of nitro functional groups to amino functional groups, and are found in a range of animal models, zebrafish (Danio rerio) excluded. Transgenic zebrafish models have been developed for tissue-specific cell ablation, which use nitroreductase to ablate specific tissues or cell types following exposure to the non-toxic pro-drug metronidazole (MTZ). When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which specifically ablates the tissue in which metabolism occurs. Uses, beyond tissue-specific cell ablation, are possible for the hepatocyte-specific Tg(l-fabp:CFP-NTR)s891 zebrafish line, including investigations of the role of nitroreductase in the toxicity of nitrated compounds. The hepatic ablation characteristics of this transgenic line were explored, in order to expand its potential uses. Embryos were exposed at 48, 72, or 96 hours post fertilization (hpf) to a range of MTZ concentrations, and the ablation profiles were compared. Ablation occurred at a 10-fold lower concentration than previously reported. Embryos were exposed to a selection of other compounds, with and without MTZ, in order to investigate alternative uses for this transgenic line. Test compounds were selected based on: their ability to undergo nitroreduction, known importance of hepatic metabolism to toxicity, and known pharmaceutical hepatotoxins. Selected compounds included nitrated polycyclic aromatic hydrocarbons (nitro-PAHs), the PAHs retene and benzo[a]pyrene, and the pharmaceuticals acetaminophen and flutamide. The results suggest a range of potential roles of the liver in the toxicity of these compounds, and highlight the additional uses of this transgenic model in toxicity testing.

show abstract

Effects of acetaminophen (paracetamol) in the embryonic development of zebrafish, Danio rerio

Cited by 65 publications

References 28 publications

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Fluorescent Transgenic Zebrafish Tg(nkx2.2a:mEGFP) Provides a Highly Sensitive Monitoring Tool for Neurotoxins

Investigating the application of a nitroreductase-expressing transgenic zebrafish line for high-throughput toxicity testing

Contact Info

Product

Resources

About