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

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.

Automated summary

This study investigated the potential damage of Salinomycin (SAL) in IPEC-J2 cells by studying the interplay between mitophagy and oxidative stress. The results showed that excessive SAL induced cell death, cell cycle arrest, and oxidative damage through the activation of the Nrf2/Keap1/HO-1 pathway. Additionally, SAL exposure also activated PINK1/Parkin-dependent mitophagy and reduced mitochondrial membrane potential. These findings suggest that targeting ROS/PINK1/Parkin-dependent mitophagy and oxidative stress could be a new protective mechanism against SAL-induced cell damage.