1. Academic Validation
  2. Dual effects of JNK activation in blood-milk barrier damage induced by zinc oxide nanoparticles

Dual effects of JNK activation in blood-milk barrier damage induced by zinc oxide nanoparticles

  • J Hazard Mater. 2020 Nov 15;399:122809. doi: 10.1016/j.jhazmat.2020.122809.
Junrong Wu 1 Xuan Lai 2 Guangman Cui 2 Qiyue Chen 3 Jia Liu 3 Yiyuan Kang 2 Yanli Zhang 3 Xiaoli Feng 3 Chen Hu 2 Longquan Shao 4
Affiliations

Affiliations

  • 1 Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, China.
  • 2 Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 3 Stomatological Hospital, Southern Medical University, Guangzhou 510515, China.
  • 4 Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, China. Electronic address: [email protected].
Abstract

Zinc oxide nanoparticles (ZnO-NPs) have been extensively applied in our daily life. Humans are at high risk of being exposed to ZnO-NPs, which induce potentially adverse health effects. Although a growing number of studies have investigated the toxic effects of ZnO-NPs, the available data concerning ZnO-NP interactions with the blood-milk barrier (BMB) remain highly limited. Herein, we systematically investigated the damage to BMB integrity induced by ZnO-NPs and the mechanisms involved. ZnO-NPs that were intravenously injected into lactating dams accumulated in the mammary gland and entered into the breast milk, inducing disruption to BMB integrity and changes in the tight junction (TJ) and adherens junction (AJ) components. Furthermore, using an in vitro BMB model composed of EpH4-Ev cells, we verified that ZnO-NP-triggered ROS generation and the activation of MKK4 and JNK are the main mechanism of cell-cell junction damage. More interestingly, JNK activation played different roles in inducing changes in the TJ and AJ complex, and these effects did not need to activate the downstream c-Jun. These data provide more information for understanding ZnO-NP interactions with the BMB and raise concern for the daily use and the intravenous use of ZnO-NPs by lactating mothers.

Keywords

Adherens junction; Blood-milk barrier; JNK; Tight junction; Zinc oxide nanoparticles.

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