Targeting ACSL4: A potential strategy to alleviate deoxynivalenol-mediated intestinal ferroptosis, oxidative stress, and immunosuppression in Channa argus

In the present study, we evaluated the effects of deoxynivalenol (DON) on intestinal oxidative stress, immunity, ferroptosis, and endoplasmic reticulum stress in Channa argus . Furthermore, we investigated the mechanism underlying DON-induced cytotoxicity by inhibiting ACSL4 in macrophages. In vivo analysis demonstrated DON inhibits growth and even leading to increased mortality. DON induces intestinal ROS and iron ion accumulation, thereby causing endoplasmic reticulum dysfunction and triggering oxidative stress and ferroptosis. This process is accompanied by decreased levels of ferroptosis-inhibiting proteins (GPX4, FPN1, and FSP1), along with increased ACSL4 and ROS levels. Furthermore, DON-induced ROS accumulation elicits endoplasmic reticulum dysfunction and drives the progression of immunosuppression and inflammation. In vitro analysis demonstrated that inhibition of ACSL4 affects macrophage activity as well as ROS and ATP levels, representing a potential intervention strategy to restore immune cell function. This study demonstrates that targeting ACSL4 may serve as a potential strategy for alleviating DON-mediated intestinal injury in C. argus .