Exposure to salinomycin dysregulates interplay between mitophagy and oxidative response to damage the porcine jejunal cells

• Published in: The Science of the total environment 2023-11, Vol.900, p.166441-166441, Article 166441
• Main Authors: Wang, Xiaoyu, Tian, Xiaomin, Yan, Huilin, Zhu, Tingting, Ren, Hao, Zhou, Yufeng, Zhao, Donghao, Xu, Dan, Lian, Xinlei, Fang, Liangxing, Yu, Yang, Liao, Xiaoping, Liu, Yahong, Sun, Jian
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Mitophagy; Nrf2/Keap1 pathway; Oxidative stress; PINK1/Parkin pathway; Salinomycin
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.166441

Salinomycin (SAL) has caused widespread pollution as a feed additive and growth promoter in livestock such as pigs, exerting a negative impact on public health. The toxicity mechanism of SAL has been widely studied in chickens, but the underlying mechanisms of SAL-induced toxicity to pigs and the ecosystem remain undefined. In this study, we explored the potential damage of SAL in IPEC-J2 cells to identify the effects of excessive SAL on the interplay between mitophagy and oxidative stress. The results showed that a concentration-dependent response was observed for SAL in altering cellular morphology and inducing cell death in IPEC-J2 cells, including the induction of cell cycle arrest and lactic dehydrogenase (LDH) release. Meanwhile, we found that excessive SAL led to oxidative damage by activating the Nrf2/Keap1/HO-1 pathway, accompanied by reactive oxygen species (ROS) elevation and the reduction of antioxidant enzyme activity. We also found that PINK1/Parkin-dependent mitophagy was activated by SAL exposure, particularly with mitochondrial membrane potential reduction. Interestingly, SAL-induced oxidative damages were prevented after the autophagy inhibitor 3-methyladenine (3-MA) treatment, and mitophagy was alleviated following ROS scavenger (N-acetylcysteine, NAC) treatment. Overall, our findings showed that SAL stimulated oxidative stress and mitophagy in IPEC-J2 cells resulting in cellular injury, and there was a strong connection between SAL-induced oxidative stress and mitophagy. Targeting ROS/PINK1/Parkin-dependent mitophagy and oxidative stress could be a novel protective mechanism in SAL-induced cell damage. Excessive salinomycin (SAL) could induce cytotoxicity through the induction of oxidative damage and mitophagy in IPEC-J2 cells. Targeting ROS/PINK1/Parkin-dependent mitophagy and oxidative stress could ameliorate SAL-induced cytotoxicity. [Display omitted] •Excessive salinomycin (SAL) could cause cytotoxicity in IPEC-J2 cells.•SAL could lead to oxidative damage through the Nrf2/Keap1/HO-1 pathway.•PINK1/Parkin-dependent mitophagy was activated by SAL exposure.•There was an interplay between SAL-induced oxidative stress and mitophagy.•Targeting ROS/PINK1/Parkin pathway could alleviate cell damage caused by SAL.