Effects of trabectedin in the zebrafish Danio rerio: from cells to larvae

Damasceno, Évila Pinheiro; Charlie-Silva, Ives; Machado-Santelli, Gláucia Maria; Garnique, Anali M. B.; Machado-Neto, João Agostinho; Teixeira, Simone Aparecida; Jimenez, Paula Christine; Carneiro, Diana; Soares, Amadeu M.V.M.; Costa-Lotufo, L. V.; Loureiro, Susana; Pavlaki, Maria D.

doi:10.1016/j.envadv.2022.100208

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…Additionally, at sublethal concentrations (LOEC of 42.66 g L -1 ), trabectedin caused developmental abnormalities such as somite alterations, pericardial edema, tail malformations, and lack of equilibrium (8), while even at a concentration 2000 times higher, cytarabine did not induce any measurable effects. Figure 1.…”

Section: Effects On Embryonic Developmentmentioning

confidence: 97%

“…No toxicity (LC 50 > 100 mg L -1 ) has been also associated to both acute and chronic exposure of zebrafish adult and larvae to 5fluorouracil (5-FU) (3), an extensively used antimetabolite antineoplastic that generally displays higher toxicity than cytarabine (2,13). On the other hand, trabectedin, a highly cytotoxic chemotherapeutic drug with DNA damage properties, was far more toxic than both antimetabolites drugs, cytarabine, and 5-FU, with LC 50 values of 95.61 and 77.55 g L -1 after 24h and 96h exposure, respectively (8).…”

Section: Effects On Embryonic Developmentmentioning

confidence: 99%

“…AAs are inherently cytotoxic compounds, inducing genotoxic, mutagenic, carcinogenic, endocrine disruption, and teratogenic effects in several non -target organisms (2). Recently, our group reported that trabectedin, a DNA damage agent used mainly in sarcoma treatment, is toxic using in vivo and in vitro zebrafish models (8). Therefore, the occurrence and persistence of these AA in the environment may represent a potential risk factor for biota.…”

Section: Introductionmentioning

confidence: 99%

“…. In recent years, the assessment of aquatic toxicity of pharmaceuticals using fish has significantly increased (14) and the teleost zebrafish Danio rerio has been recurrently employed in ecotoxicological studies (15,16,17,8). Therefore, the present study aimed to evaluate the cytarabine lethal and sublethal effects in the zebrafish model, to assess potential ecotoxicological effects in non-target species.…”

Section: Introductionmentioning

confidence: 99%

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Behavioral and biochemical alterations in zebrafish model suggests AChE as a potential target for cytarabine neurotoxicological effects

Charlie-Silva¹,

Ferreira

Damasceno

et al. 2022

Preprint

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Due to their general cytotoxic effects, anticancer drugs pose a great risk to aquatic species, yet they have been among the least studied groups of drugs regarding their environmental impact. The present study aimed to identify the effects of the antileukemia drug cytarabine, also known as cytosine arabinoside (ara-C), on the development and neurobehavior of zebrafish larvae. Zebrafish eggs were exposed to cytarabine to assess survival, embryonic malformations, locomotor activity, DNA damage, and biochemical alterations. No mortality, teratogenicity, or genotoxicity was detected in zebrafish larvae up to 100 mg L-1. However, cytarabine decreased the total distance traveled by zebrafish under dark conditions, suggesting depression-like behavior in treated larvae. Furthermore, it was demonstrated that cytarabine exposure increased lipid peroxidation (LPO) and acetylcholinesterase (AChE) activity, while it inhibited catalase (CAT) activity. Multivariate analysis suggested that both AChE and LPO correlated to behavioral changes, while molecular docking and dynamics simulations suggested a direct binding and stability of cytarabine to AChE. Further analyses of the effects of this anticancer compound in the cholinergic transmission are in progress to allow a better understanding of its neurotoxicity.

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Section: Effects On Embryonic Developmentmentioning

confidence: 97%

Section: Effects On Embryonic Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Behavioral and biochemical alterations in zebrafish model suggests AChE as a potential target for cytarabine neurotoxicological effects

Charlie-Silva¹,

Ferreira

Damasceno

et al. 2022

Preprint

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“…Although the presence of antineoplastic agents in the environment is acknowledged, information regarding their related biological effects on organisms is scarce. Considering the cytotoxic and cytostatic mechanisms of action of anticancer drugs (Damasceno et al, 2022), which attack both tumor and healthy cells indiscriminately, all eukaryotic organisms are vulnerable to adverse effects resulting from exposure to antineoplastic agents.…”

Section: Introductionmentioning

confidence: 99%

Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms

Ribeiro

Lotufo

Loureiro

et al. 2022

Enviro Toxic and Chemistry

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Pharmaceutical compounds represent a class of emerging contaminants present in the environment. Their intense (and increasing) use in human and veterinary medicine leads to their discharge, mainly via human excretion, into wastewater treatment plants where their removal is inefficient. A specific class of pharmaceuticals used to fight cancer, known as antineoplastic or anticancer drugs, has gained increased attention regarding their possible environmental hazard due to their pharmacological properties, which include the nonselective targeting of DNA replication mechanisms and cell division processes, potentially inducing cell apoptosis. To date, there is limited information concerning the effects of anticancer drugs and/or their metabolites in species inhabiting freshwater environments, let alone marine and estuarine compartments. In the present review, we aimed to assemble information regarding the impact that anticancer drugs have on biological traits of marine species, to identify gaps in the current environmental hazard assessment, and to make recommendations to promote an efficient environmental hazard assessment of anticancer drugs in the marine environment. Environ Toxicol Chem 2022;41:1793–1807. © 2022 SETAC

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Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms

Damasceno

Ribeiro

Costa-Lotufo

et al. 2023

Environmental Toxicology and Pharmacology

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Effects of trabectedin in the zebrafish Danio rerio: from cells to larvae

Cited by 5 publications

References 46 publications

Behavioral and biochemical alterations in zebrafish model suggests AChE as a potential target for cytarabine neurotoxicological effects

Behavioral and biochemical alterations in zebrafish model suggests AChE as a potential target for cytarabine neurotoxicological effects

Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms

Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms

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