Combined Negative Effects of Microplastics and Plasticizer DEHP: the Increased Release of Nets Delays Wound Healing

Abstract Introduction: Environmental pollutants microplastics (MPs) and di (2-ethyl) hexyl phthalate (DEHP) can cause damage to multiple organs by causing oxidative stress. Oxidative stress participates in the healing of skin wounds through the release of neutrophil extranets (Nets). Here, we studied the effects of DEHP and MPs on skin wound healing in mice after single and combined exposure for 1 month. Results: The results showed that MPs delayed the healing of skin wounds, and the combination of the two delayed wound healing more significantly. The results of in vivo and in vitro experiments showed that the release of oxidative stress and Nets in the single exposure group increased, and the combined exposure group increased more. Further mechanism studies showed that the skin chemokines of the single exposure group increased, the NF-κB pathway was activated, the Wnt pathway was inhibited, and the epidermal growth factor and fibrosis-related indicators decreased. The combined exposure group showed a more obvious trend. Conclusion: In summary, the above results indicate that DEHP combined with MPs induces an increase in the release of Nets by causing excessive skin ROS production and increases the expression of chemokines and interferes with the expression of healing factors by regulating the NF-κB and Wnt pathways.