Emamectin benzoate and nanoplastics induce PANoptosis of common carp (Cyprinus carpio) gill through MAPK pathway.

Emamectin benzoate (EMB) is a pesticide that is frequently used. Nanoplastics (NPs) are a recently identified class of pollutants that are ubiquitous in the environment. In the aquatic environment, NPs can appear together with EMB, which may exacerbates the damage to water and aquatic organisms. However, the damage and mechanism of EMB and NPs to the gill tissue of common carp (Cyprinus carpio) remain unclear. Therefore, an EMB or/NPs exposure model was constructed to explore the mechanism of EMB or/NPs exposure on carp gill damage. This study was done by immunofluorescence, RT-qPCR, Western blot and other methods. Both in vitro and in vivo data indicated that EMB or NPs exposure could lead to gill tissue destruction, oxidative stress with the increased of ROS fluorescence intensity, MDA and HO content, and the decreased CAT and GSH-PX activity, and the activation of MAPK pathway. Subsequently, PANoptosomes were activated with the up-regulated mRNA and protein expression of RIPK-1, Caspase-1,NLRP3, ACS, RIPK-3, Caspase-8, resulting in PANoptosis including the increased GSDMD, Caspase-3, MLKL expression. Notably, the results following combined exposure were more pronounced than those observed following exposure alone. The addition of N-acetylcysteine (NAC) and 3-methylindole (3-MI) further evidenced that EMB or/and NPs exposure can induce gill damage via the ROS/MAPK/PANoptosis pathway. Therefore, the present study reveals that EMB or/NPs exposure induces PANoptosis in carp gill by activating ROS/p38/MAPK signaling.