Comparative transcriptomics of salinomycin molecular toxicity in chicken and turkey.

Salinomycin (Sal) is an antiparasitic agent used in veterinary medicine and is characterized by low therapeutic index and high toxicity. Among poultry, chickens are resistant to Sal toxicity, but turkeys are considered susceptible. However, underlying mechanisms of Sal toxicity are poorly understood. This comparative transcriptomic study aimed to determine molecular toxicity mechanisms of Sal in both species. We conducted two experiments on chickens and turkeys exposed to Sal (0.9 mg/kg b.w/day) vs. unexposed. Heart and liver (n = 6) were collected post-mortem (chicken 5th; turkey 13th week). RNA was isolated and examined by RNA-seq to identify differentially expressed (DE) genes and pathways. Number of significant DE genes in chicken was 673 (heart) and 3049 (liver), and in turkey, 485 (heart) and 2337 (liver). Enrichment analysis revealed that Sal exposure activated platelet signaling in chicken heart, while it induced cell cycle arrest in turkey heart. In liver, impaired Sal biotransformation was determined as a shared response. In turkey liver, we determined that extracellular matrix pathway was upregulated, which could indicate liver fibrosis. Our findings demonstrate that molecular toxicity of Sal differs between species and turkey confirmed being more susceptible to Sal toxicity also at molecular level via induced cell cycle arrest and fibrosis.