Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae

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Padovani, Barbara Nunes ; Fenero, Camila Morales ; Paredes, Lais Cavalieri ; do Amaral, Mariana Abrantes ; Dominguez-Amorocho, Omar ; Cipelli, Marcella ; Gomes, Juliana Moreira Mendonca ; da Silva, Eloisa Martins ; Silva, Luisa Menezes ; de Souza Vieira, Raquel ; Pereira, Mariana Tominaga ; Cruz, Mario Costa ; Camara, Niels Olsen Saraiva

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 4, p. 16-pg., 2024-02-01.

Resumo

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. (AU)

• Processo FAPESP: 17/05264-7 - Metabolismo celular, microbiota e sistema imune: novos paradigmas na fisiopatologia das doenças renais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/21644-9 - Inflamação induzida pela obesidade, alterações da microbiota e seus efeitos no sistema nervoso entérico: estudo num modelo experimental de zebrafish.
• Beneficiário: Camila Idelí Morales Fénero
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/12833-6 - Efeito da restrição calórica na sinalização via cGAS-STING na Lesão Renal Aguda no Zebrafish
• Beneficiário: Barbara Nunes Padovani
• Modalidade de apoio: Bolsas no Brasil - Doutorado