2. Academic Validation
  3. Hexavalent chromium disrupts the skin barrier by targeting ROS-mediated mitochondrial pathway apoptosis in keratinocytes

Hexavalent chromium disrupts the skin barrier by targeting ROS-mediated mitochondrial pathway apoptosis in keratinocytes

  • Chem Biol Interact. 2023 May 3;110523. doi: 10.1016/j.cbi.2023.110523.
Cheng Wang 1,  Hongqi Shang 1,  Shuyu Zhang 1,  Xiangkun Wang 1,  Defeng Liu 1,  Mingyue Shen 1,  Ning Li 1,  Yunxuan Jiang 1,  Kai Wei 2,  Ruiliang Zhu 3
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China.
  • 2 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China. Electronic address: [email protected].
  • 3 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China. Electronic address: [email protected].
PMID: 37146930 DOI: 10.1016/j.cbi.2023.110523
Abstract

Hexavalent chromium (Cr(VI)), a toxic heavy metal, is ubiquitous in daily life. Exposure to this toxic substance in occupational settings can cause dermatitis and Cancer. As the body's largest organ, the skin plays a crucial role in protecting the organism against external aggressions. While previous studies have focused on the effects of Cr(VI) on skin inflammation, this study investigates the potential toxicity of Cr(VI) from the skin barrier and integrity perspective. The in vivo results of this study showed that mice exposed to Cr(VI) experienced skin deterioration and hemorrhaging, as well as a reduction in the thickness of the collagen fiber layer. TUNEL and Occludin staining results revealed that Cr(VI)'s toxicity primarily targeted keratinocytes. Experiments in vitro demonstrated that Cr(VI) treatment decreased the activity of HaCaT cells, altered cell morphology, and increased LDH secretion. Further research revealed that Cr(VI) could modify membrane permeability, impair membrane integrity, and reduce the protein expression of ZO-1 and Occludin. In addition, it was discovered that Cr(VI) promoted cell Apoptosis and inhibited Akt activation. However, the addition of a Caspase Inhibitor and an Akt Activator prevented Cr(VI)-induced injury to the cell membrane barrier, indicating that Apoptosis plays a crucial role in this process. The addition of three apoptotic pathway inhibitors, confirmed that Cr(VI) damaged the cell barrier through ROS-mediated mitochondrial pathway Apoptosis. Moreover, the use of a ROS inhibitor significantly reduced Cr(VI)-induced Apoptosis and cell barrier injury. In conclusion, this study provides an experimental foundation for the treatment of skin injury caused by Cr(VI).

Keywords

Barrier damage; Hexavalent chromium; Keratinocytes; Mitochondrial pathway apoptosis; ROS.

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