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- Title
Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae.
- Authors
Padovani, Barbara Nunes; Morales Fénero, Camila; Paredes, Lais Cavalieri; Amaral, Mariana Abrantes do; Domínguez-Amorocho, Omar; Cipelli, Marcella; Gomes, Juliana Moreira Mendonça; da Silva, Eloisa Martins; Silva, Luísa Menezes; Vieira, Raquel de Souza; Pereira, Mariana Tominaga; Cruz, Mario Costa; Câmara, Niels Olsen Saraiva
- Abstract
Cisplatin is an antineoplastic agent used to treat various tumors. 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.
- Subjects
BRACHYDANIO; ZEBRA danio; LARVAE; CISPLATIN; ACUTE kidney failure; ANTINEOPLASTIC agents; INFLAMMATORY mediators; ANIMAL locomotion
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 4, p2363
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25042363