The Role of Iron Metabolism in Sepsis-associated Encephalopathy: a Potential Target

Abstract

Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction secondary to infection, and the severity can range from mild delirium to deep coma. Disorders of iron metabolism have been proven to play an important role in a variety of neurodegenerative diseases by inducing cell damage through iron accumulation in glial cells and neurons. Recent studies have found that iron accumulation is also a potential mechanism of SAE. Systemic inflammation can induce changes in the expression of transporters and receptors on cells, especially high expression of divalent metal transporter1 (DMT1) and low expression of ferroportin (Fpn) 1, which leads to iron accumulation in cells. Excessive free Fe²⁺ can participate in the Fenton reaction to produce reactive oxygen species (ROS) to directly damage cells or induce ferroptosis. As a result, it may be of great help to improve SAE by treatment of targeting disorders of iron metabolism. Therefore, it is important to review the current research progress on the mechanism of SAE based on iron metabolism disorders. In addition, we also briefly describe the current status of SAE and iron metabolism disorders and emphasize the therapeutic prospect of targeting iron accumulation as a treatment for SAE, especially iron chelator. Moreover, drug delivery and side effects can be improved with the development of nanotechnology. This work suggests that treating SAE based on disorders of iron metabolism will be a thriving field.

Keywords: Fenton Reaction; Iron Chelator; Iron Metabolism; Nanotechnology; Sepsis-associated Encephalopathy.