Development of a convenient and rapid screening zebrafish model to investigate lethal effects and immunocompromised states of uremic toxins.

Abstract

BACKGROUND: Uremia is characterized by high mortality and immune dysfunction owing to the accumulation of uremic toxins. Traditional rodent models are complex and time consuming. This study aimed to develop a simple and rapid zebrafish model for investigating the toxicological effects of uremic toxins. METHODS: Uremic solutions containing small (SUT) and medium-to-large (MLUT) uremic toxins were prepared using waste solution of peritoneal dialysis by a dialysis method. Wild-type zebrafish larvae were used to assess mortality, whereas transgenic (TG) (zlyz:EGFP) zebrafish, with macrophages labeled with green fluorescent protein, were used to evaluate immune status through macrophage migration assays. RESULTS: The mortality rates were significantly higher in the SUT- and MLUT-treated groups than in the controls, with SUT showing the strongest lethal effect. Macrophage migration was significantly inhibited in both SUT- and MLUT-treated groups, indicating an immunocompromise. This model effectively mimicked the lethal and immunosuppressive effects of uremia. CONCLUSION: This zebrafish model provides a simple and rapid platform for studying the toxicological effects of uremic toxins and evaluating potential therapeutic interventions.