Effects of marine pharmaceuticals in zebrafish and ZFL cell line - emphasis

• Grant number: 18/07098-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: Fundação para a Ciência e a Tecnologia (FCT)
• Principal Investigator: Leticia Veras Costa Lotufo
• Grantee: Leticia Veras Costa Lotufo
• Principal researcher abroad: Maria Pavlaki
• Institution abroad: Universidade de Aveiro (UA), Portugal
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Anelize Bauermeister ; Marcelo José Pena Ferreira ; Marcelo Marucci Pereira Tangerina ; Paula Christine Jimenez
• Associated scholarship(s): 19/19939-1 - Effects of marine pharmaceuticals in ZFL cell line, BP.PD

Abstract

Pharmaceuticals are considered emerging organic contaminants and concerns on their environmental impact have been raised in the last decades as they have been detected in the environment. Pharmaceuticals enter the aquatic environment mainly due to WWTP effluent discharges or after direct application for veterinary purposes, such as in aquaculture and animal-infection preventing. A commonly found group of pharmaceuticals in the aquatic environment is antineoplastics. Antineoplastics is one of the least studied groups concerning environmental impact and have been considered to represent specific risks to non-target aquatic species due to their mode of action (MoA). They are biologically active compounds that interact with a target molecule and though encountered at low concentrations in the environment (ng/L to ¼g/L), may promote toxicity through different mechanisms or affect organisms with the same target molecule. Such distinct characteristics that antineoplastics possess make them unpredictable in terms of environmental effects. Therefore, the need of an in-depth assessment of such effects is necessary for an environmental risk assessment to promote and develop a risk-based regulation and develop standardized testing procedures for antineoplastics. There are 4 main questions that will be addressed in the EMPHASIS project proposed in this application.Q.1: Do marine pharmaceuticals (MPs) cause eco-, geno- and cytotoxicity to ZF and ZFL cell line?Q.2: What is the bioconcentration potential of MPs to ZF and ZFL cell line?Q.3: How do MPs affect the microbiota (bacterial and fungal communities? composition and number) in ZF?Q.4: How the MPs are metabolized by ZF and ZFL cell line?To address those questions, the EMPHASIS project aims at evaluating i) the effects of clinic antineoplastics (two marine-derived ones, trabectedin and eribulin mesylate) and novel compounds with anticancer properties using in vivo and in vitro models, ii) the potential of cell lines to serve as alternative eco-toxicological models by validating them with the use of in vivo animal models and iii) to evaluate and validate the ecotoxicological effects of new potential MPs when compared to clinic MPs. Finally, with the use of the Adverse Outcome Pathway (AOP) approach, the link between several key events and the effects at different organizational levels will provide robust information for use in regulatory risk assessment. (AU)

Scientific publications

(11)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CHARLIE-SILVA, IVES; FEITOSA, NATALIA MARTINS; MENDONCA GOMES, JULIANA MOREIRA; DE MELO HOYOS, DANIELA CHEMIM; MATTIOLI, CRISTIANO CAMPOS; ETO, SILAS FERNANDES; FERNANDES, DAYANNE CARLA; DE ANDRADE BELO, MARCO ANTONIO; SILVA, JULIANA DE OLIVEIRA; BRANCO DE BARROS, ANDRE LUIS; et al. Potential of mucoadhesive nanocapsules in drug release and toxicology in zebrafish. PLoS One, v. 15, n. 9, SEP 24 2020. (19/19939-1, 13/25971-9, 18/07098-0)

VENTURA FERNANDES, BIANCA H.; FEITOSA, NATALIA MARTINS; BARBOSA, ANA PAULA; BOMFIM, CAMILA GASQUE; GARNIQUE, ANALI M. B.; ROSA, IVANA F.; RODRIGUES, MAIRA S.; DORETTO, LUCAS B.; COSTA, DANIEL F.; CAMARGO-DOS-SANTOS, BRUNO; et al. oxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health. Science of The Total Environment, v. 813, MAR 20 2022. (19/00195-2, 18/07098-0, 20/05761-3, 17/17303-7, 20/04680-0, 14/04294-1, 19/21739-0, 19/19939-1, 19/18356-2, 19/14285-3, 19/12234-2)

BAUERMEISTER, ANELIZE; MANNOCHIO-RUSSO, HELENA; COSTA-LOTUFO, LETICIA V.; JARMUSCH, ALAN K.; DORRESTEIN, PIETER C.. ass spectrometry-based metabolomics in microbiome investigation. NATURE REVIEWS MICROBIOLOGY, v. 20, n. 3, SEP 2021. (15/17177-6, 18/24865-4, 18/07098-0)

BELO, MARCO A. A.; OLIVEIRA, MELQUE F.; OLIVEIRA, SUSANA L.; ARACATI, MAYUMI F.; RODRIGUES, LETICIA F.; COSTA, CAMILA C.; CONDE, GABRIEL; GOMES, JULIANA M. M.; PRATA, MARIANA N. L.; BARRA, AYSLAN; et al. Zebrafish as a model to study inflammation: A tool for drug discovery. BIOMEDICINE & PHARMACOTHERAPY, v. 144, DEC 2021. (13/25971-9, 19/19939-1, 18/07098-0)

GONCALVES, SANDRA F.; SILVA, ANA RITA R.; PAVLAKI, MARIA D.; MORGADO, RUI G.; LOUREIRO, SUSANA. Site-specific hazard evaluation for improved groundwater risk assessment. Chemosphere, v. 274, JUL 2021. (18/07098-0)

ROSA, IVANA F.; PECANHA, ANA P. B.; CARVALHO, TABATA R. B.; ALEXANDRE, LEONARDO S.; FERREIRA, VINICIUS G.; DORETTO, LUCAS B.; SOUZA, BEATRIZ M.; NAKAJIMA, RAFAEL T.; DA SILVA, PATRICK; BARBOSA, ANA P.; et al. Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 7, p. 22-pg., 2023-04-01. (20/05761-3, 19/21739-0, 14/04294-1, 19/19939-1, 20/15237-0, 18/07098-0, 21/06742-5)

DAMASCENO, EVILA PINHEIRO; RIBEIRO, FABIANNE; COSTA-LOTUFO, LETICIA, V; SOARES, AMADEU M. V. M.; PAVLAKI, MARIA D.; LOUREIRO, SUSANA. Assessing the impact of antineoplastic drugs in the aquatic environment: State of the art and future perspective for freshwater organisms. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, v. 99, p. 12-pg., 2023-03-23. (15/17177-6, 18/07098-0)

RIBEIRO, FABIANNE; COSTA-LOTUFO, LETICIA; LOUREIRO, SUSANA; PAVLAKI, MARIA D.. Environmental Hazard of Anticancer Drugs: State of the Art and Future Perspective for Marine Organisms. Environmental Toxicology and Chemistry, v. 41, n. 8, p. 15-pg., 2022-07-08. (18/07098-0, 15/17177-6)

SANTANA, LIGIA M. B. M.; DAMASCENO, EVILA PINHEIRO; LOUREIRO, SUSANA; SOARES, AMADEU M. V. M.; POUSAO-FERREIRA, PEDRO; ABESSA, DENIS M. S.; MARTINS, ROBERTO; PAVLAKI, MARIA D.. An Easy-to-Use Histological Technique for Small Biological Samples of Senegalese Sole Larvae. APPLIED SCIENCES-BASEL, v. 13, n. 4, p. 12-pg., 2023-02-01. (20/03004-0, 18/07098-0)

CARNEIRO, DIANA; DAMASCENO, EVILA PINHEIRO; FERREIRA, VIOLETA; CHARLIE-SILVA, IVES; TEDIM, JOAO; MAIA, FREDERICO; LOUREIRO, SUSANA; MARTINS, ROBERTO; PAVLAKI, MARIA D.. Zn-Al layered double hydroxides induce embryo malformations and impair locomotion behavior in Danio rerio. NANOIMPACT, v. 30, p. 12-pg., 2023-02-27. (19/19939-1, 18/07098-0)

SILVA, ANA RITA R.; GONCALVES, SANDRA F.; PAVLAKI, MARIA D.; MORGADO, RUI G.; SOARES, AMADEU M. V. M.; LOUREIRO, SUSANA. ixture toxicity prediction of substances from different origin sources in Daphnia magn. Chemosphere, v. 292, APR 2022. (18/07098-0)