Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases

Abstract

Oxidative stress results from a disturbed balance between oxidation and antioxidant systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) may be either harmful or beneficial to the cells. Ion channels are transmembrane proteins that participate in a large variety of cellular functions and have been implicated in the development of a variety of diseases. A significant amount of the available drugs in the market targets ion channels. These proteins have sulfhydryl groups of cysteine and methionine residues in their structure that can be targeted by ROS and RNS altering channel function including gating and conducting properties, as well as the corresponding signaling pathways associated. The regulation of ion channels by ROS has been suggested to be associated with some pathological conditions including liver diseases. This review focuses on understanding the role and the potential association of ion channels and oxidative stress in liver diseases including fibrosis, alcoholic liver disease, and cancer. The potential association between ion channels and oxidative stress conditions could be used to develop new treatments for major liver diseases.

Figure 1

Participation of ion channels in HSCs activation during fibrogenesis. Ion channel upregulation including TRPM7, TRPV4, P2X₇, and ASIC1a has been reported during the activation of HSCs, which is a major event during fibrogenesis. Blocking these channels with pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS), 2-aminoethoxydiphenyl borate (2-APB), and Gd³⁺; ruthenium red (Ru); PcTX1 or A438970 reduces proliferation of HSCs and production of profibrotic markers (α-SMA, Col1α1), preventing the progression of fibrosis.