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

by Selleckchem | Jul 17 2023

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).

Comments:

The study you described focuses on investigating the potential toxicity of hexavalent chromium (Cr(VI)) from the perspective of skin barrier function and integrity. Previous studies have primarily explored the effects of Cr(VI) on skin inflammation, but this study aims to examine its impact on the skin's structural and functional aspects.

The study utilized both in vivo and in vitro experiments to assess the effects of Cr(VI) exposure. In the in vivo experiments using mice, it was observed that exposure to Cr(VI) led to skin deterioration, hemorrhaging, and a reduction in the thickness of the collagen fiber layer. TUNEL and Occludin staining techniques were employed to identify the primary target of Cr(VI) toxicity, which was found to be keratinocytes, the predominant cells in the epidermis.

In vitro experiments were conducted using HaCaT cells, which are a commonly used human keratinocyte cell line. The results showed that treatment with Cr(VI) decreased the activity of HaCaT cells, altered their morphology, and increased the secretion of lactate dehydrogenase (LDH), an indicator of cell damage.

Further investigation revealed that Cr(VI) could modify membrane permeability, impair membrane integrity, and reduce the protein expression of ZO-1 and Occludin. ZO-1 and Occludin are proteins involved in maintaining tight junctions between cells, contributing to the integrity of the skin barrier.

The study also found that Cr(VI) promoted cell apoptosis (programmed cell death) and inhibited the activation of AKT, a protein involved in cell survival and proliferation. However, when a caspase inhibitor (which blocks the activity of caspases, enzymes involved in apoptosis) and an AKT activator were added, they prevented Cr(VI)-induced injury to the cell membrane barrier. This suggests that apoptosis plays a crucial role in the process of skin barrier damage caused by Cr(VI).

To further understand the mechanism of Cr(VI)-induced apoptosis and cell barrier injury, three apoptotic pathway inhibitors were employed. The results confirmed that Cr(VI) damages the cell barrier through a pathway involving reactive oxygen species (ROS)-mediated mitochondrial apoptosis.

Moreover, the use of a ROS inhibitor significantly reduced Cr(VI)-induced apoptosis and cell barrier injury, indicating that ROS generation is involved in the toxic effects of Cr(VI) on the skin barrier.

In summary, this study provides experimental evidence for the treatment of skin injury caused by Cr(VI). The findings highlight the detrimental effects of Cr(VI) on skin barrier integrity, primarily targeting keratinocytes and involving apoptosis and ROS-mediated mitochondrial pathway activation. This research contributes to a better understanding of the toxic effects of Cr(VI) on the skin and may aid in the development of strategies to mitigate or treat skin injuries associated with Cr(VI) exposure.