Salinomycin, as a polyether ionophore antibiotic, is extensively used as a feed additive against coccidiosis in poultry and as a growth promoter of ruminants worldwide. Owing to its narrow therapeutic index, numerous intoxication have been reported in target/non-target animals by overdosage, misuse or drug interactions as well as human who consumed salinomycin accidently. Salinomycin-induced cardiotoxicity in chicken and non-target animals is considered as a major contributor to animal death. In the current study, we aim to elucidate the underlying mechanism of its myocardial toxicity using primary chicken myocardial cell as an in vitro model. The results showed that salinomycin altered cellular morphology and induced cell death in a concentration-dependent manner. Salinomycin treatment elevated the permeability of the cell membrane and leaded to the efflux of enzymes, including creatine kinase (CK) and lactate dehydrogenase (LDH). Flow cytometry analysis indicated the number of apoptotic cells increased significantly by salinomycin exposure. Furthermore, caspase-3 and caspase-9 were activated at gene and protein level rather than caspase-8, along with the up-regulation of apoptosis genes Bax, Cytochrome C, Apoptotic peptidase activating factor 1 (Apaf-1) and the down-regulation of Bcl-2. Salinomycin-induced mitochondrial dysfunction was accompanied by the significant decrease of mitochondrial membrane potential (MMP) and the severe ultrastructure damage. In conclusion, these findings suggest that the toxic dose of salinomycin induces severe cardiomyocytes death through mitochondria mediated apoptosis pathway.

沙利霉素是一种聚醚离子载体抗生素，被广泛用作家禽球虫病的饲料添加剂和全球反刍动物的生长促进剂。由于其狭窄的治疗指数，据报道，过量/滥用，滥用或药物相互作用以及意外食用沙利霉素的人都会在靶/非靶动物中引起大量中毒。沙利霉素在鸡和非靶标动物中引起的心脏毒性被认为是导致动物死亡的主要因素。在当前的研究中，我们旨在通过使用鸡原代心肌细胞作为体外阐明其心肌毒性的潜在机制模型。结果表明，沙利霉素以浓度依赖性方式改变细胞形态并诱导细胞死亡。盐霉素的治疗提高了细胞膜的通透性，并导致包括肌酸激酶（CK）和乳酸脱氢酶（LDH）在内的酶外排。流式细胞仪分析表明，通过沙利霉素的暴露，凋亡细胞的数量显着增加。此外，caspase-3和caspase-9在基因和蛋白质水平而不是caspase-8被激活，同时凋亡基因Bax，细胞色素C，凋亡肽酶激活因子1（Apaf-1）上调和下调。 Bcl-2的调节。沙利诺霉素诱导的线粒体功能障碍伴随着线粒体膜电位（MMP）的显着降低和严重的超微结构损害。综上所述，