Sodium hydrosulfide inhibiting endothelial cells injury and neutrophils activation via IL-8/CXCR2/ROS/NF-κB axis in type 1 diabetes mellitus rat

Aims: Hydrogen sulfide (H2S) prevents endothelial cells injury. However, the complicated mechanism of sodium hydrosulfide (NaHS, a donor that produces H2S) which inhibits the endothelial cells injury which correlated the activation of neutrophil in the type 1 diabetes mellitus (T1DM) rats has not been previously investigated. Methods and results: In the experiment, the T1DM animal model was established, the IL-1 beta, IL-8 were determined by western blotting and ELISA, the expressions of the Bax and Bcl-2 of endothelial cells and the CXCR2, CSE, phosphor-I kappa B alpha and NF-kB of neutrophils were measured by western blotting. Additionally, the concentration of serum dsDNA was tested by PicoGreen commercial Kits, changes in the H2S concentration of neutrophils were determined by Multiskan spectrum microphate spectrophotometer, the cellular ROS levels of neutrophils were detected by DCFH-DA staining and flow cytometry. The IL-1 beta, IL-8 concentration and expression increased, the endothelial cells injury which stimulated by high glucose and the concentration of dsDNA in serum increased, the expression of CXCR2, phosphor-I kappa B alpha and NF-kB increased while the expression of CSE and concentration of H2S decreased in neutrophils in the T1DM group compared to the control group. NaHS significantly inhibited the injury of endothelial cell, the production of ROS in neutrophils, reversed the expressions of CXCR2, CSE, phosphor-laci and NF-kappa B and decreased concentration of dsDNA in serum which were caused by T1DM. Conclusions: Our results demonstrated that the donor of H2S inhibits endothelial cells injury and neutrophils activation via the IL-8/CXCR2/ROS/NF-kappa B axis in T1DM rat. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study found that the donor of hydrogen sulfide, sodium hydrosulfide, can inhibit endothelial cell injury and neutrophil activation in type 1 diabetes mellitus rats through the IL-8/CXCR2/ROS/NF-kappa B axis.