Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae.
Barbara Nunes PadovaniCamila Morales FéneroLais Cavalieri ParedesMariana Abrantes do AmaralOmar Domínguez-AmorochoMarcella CipelliJuliana Moreira Mendonça GomesEloisa Martins da SilvaLuísa Menezes SilvaRaquel de Souza VieiraMariana Tominaga PereiraMario Costa CruzNiels Olsen Saraiva CamaraPublished in: International journal of molecular sciences (2024)
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.
Keyphrases
- oxidative stress
- acute kidney injury
- flow cytometry
- randomized controlled trial
- spinal cord injury
- induced apoptosis
- drosophila melanogaster
- cardiac surgery
- cardiovascular disease
- type diabetes
- poor prognosis
- adipose tissue
- coronary artery disease
- cell proliferation
- metabolic syndrome
- long non coding rna
- single molecule
- high throughput
- drug induced
- signaling pathway
- endothelial cells
- artificial intelligence
- deep learning
- skeletal muscle
- data analysis
- pi k akt