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In mammals, it can cause nephrotoxicity, tissue damage, and inflammation. The release of inflammatory mediators leads to the recruitment and infiltration of immune cells, particularly neutrophils, at the site of inflammation. Cisplatin is often used as an inducer of acute kidney injury (AKI) in experimental models, including zebrafish (Danio rerio), due to its accumulation in kidney cells. Current protocols in larval zebrafish focus on studying its effect as an AKI inducer but ignore other systematic outcomes. In this study, cisplatin was added directly to the embryonic medium to assess its toxicity and impact on systemic inflammation using locomotor activity analysis, qPCR, microscopy, and flow cytometry. Our data showed that larvae exposed to cisplatin at 7 days post-fertilization (dpf) displayed dose-dependent mortality and morphological changes, leading to a decrease in locomotion speed at 9 dpf. The expression of pro-inflammatory cytokines such as interleukin (il)-12, il6, and il8 increased after 48 h of cisplatin exposure. Furthermore, while a decrease in the number of neutrophils was observed in the glomerular region of the pronephros, there was an increase in neutrophils throughout the entire animal after 48 h of cisplatin exposure. We demonstrate that cisplatin can have systemic effects in zebrafish larvae, including morphological and locomotory defects, increased inflammatory cytokines, and migration of neutrophils from the hematopoietic niche to other parts of the body. Therefore, this protocol can be used to induce systemic inflammation in zebrafish larvae for studying new therapies or mechanisms of action involving neutrophils.<\/jats:p>","DOI":"10.3390\/ijms25042363","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T05:39:56Z","timestamp":1708321196000},"page":"2363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae"],"prefix":"10.3390","volume":"25","author":[{"given":"Barbara Nunes","family":"Padovani","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Morales F\u00e9nero","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Environmental Toxicology, Biomedical Sciences, University of California Santa, Santa Cruz, CA 95064, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lais Cavalieri","family":"Paredes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Abrantes do","family":"Amaral","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Federal University of Sao Paulo, S\u00e3o Paulo 04023062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Dom\u00ednguez-Amorocho","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Cipelli","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Moreira Mendon\u00e7a","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Developmental & Molecular Biology, Albert Einstein College of Medicine, New York, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloisa Martins","family":"da Silva","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Federal University of Sao Paulo, S\u00e3o Paulo 04023062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u00edsa Menezes","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel de Souza","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Tominaga","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario Costa","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-1248","authenticated-orcid":false,"given":"Niels Olsen Saraiva","family":"C\u00e2mara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, S\u00e3o Paulo 05508000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1200\/JCO.21.01293","article-title":"Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II\/III Randomized Controlled Trial","volume":"40","author":"Kiyota","year":"2022","journal-title":"J. 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