Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na+/H+ exchanger

Figure 1 Na⁺/H⁺ exchanger overstimulation and its outcomes. Physiologically, the Na⁺/H⁺ exchanger (NHE) causes Na⁺ to flow inward and H⁺ to flow outward. When the intracellular pH falls, NHE is activated, raising the intracellular pH to its physiological level. NHE activity decreases as the intracellular pH increases. When NHE is overstimulated, increased Na⁺ in the cell activates the reverse Na⁺/Ca²⁺ exchanger and Ca²⁺ flows inward. The increased H⁺ in the extracellular area causes chain redox reactions and an inwards H⁺ influx. Reactive oxygen species increase, and ATP depletion inhibits Na+/K+-ATPase. As a result, hepatocytes are damaged and eventually die. NCE: Na⁺/Ca²⁺ exchanger; NHE: Na⁺/H⁺ exchanger; NKA: Na⁺/K⁺-ATPase; RNCE: Reverse Na⁺/Ca²⁺ exchanger; ROS: Reactive oxygen species.