Ekinci İlksen Berfin, Sławińska Anna, Żukowski Kacper, Olejnik Małgorzata
Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Gagarina 7, 87-100, Toruń, Poland.
Department of Cattle Breeding, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice n. Kraków, Poland.
Sci Rep. 2025 Jul 1;15(1):21586. doi: 10.1038/s41598-025-08812-7.
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.
盐霉素（Sal）是一种用于兽医学的抗寄生虫药物，其特点是治疗指数低且毒性高。在家禽中，鸡对盐霉素毒性具有抗性，但火鸡被认为易受影响。然而，盐霉素毒性的潜在机制尚不清楚。这项比较转录组学研究旨在确定盐霉素在这两个物种中的分子毒性机制。我们对暴露于盐霉素（0.9毫克/千克体重/天）和未暴露的鸡和火鸡进行了两项实验。在死后（鸡第5周；火鸡第13周）采集心脏和肝脏（n = 6）。分离RNA并通过RNA测序进行检测，以鉴定差异表达（DE）基因和通路。鸡中显著差异表达基因的数量在心脏中为673个，在肝脏中为3049个；在火鸡中，心脏中为485个，肝脏中为2337个。富集分析表明，盐霉素暴露激活了鸡心脏中的血小板信号传导，而在火鸡心脏中诱导了细胞周期停滞。在肝脏中，盐霉素生物转化受损被确定为共同反应。在火鸡肝脏中，我们确定细胞外基质通路被上调，这可能表明肝纤维化。我们的研究结果表明，盐霉素的分子毒性在不同物种之间存在差异，并且通过诱导细胞周期停滞和纤维化，火鸡在分子水平上也被证实对盐霉素毒性更敏感。
