Fig. 12.

Proposed mechanisms by which Mg regulates CIS-induced acute kidney injury (AKI). Mg deficiency leads to enhanced renal CIS accumulation via decreased efflux transporter expression and increased CIS-induced inflammation and oxidative stress with reduced ATP levels in the kidneys. Activated signaling pathways, including ERK1/2, STAT3, and p53, associated with inflammation and oxidative stress merge to promote renal cell apoptosis/necrosis, resulting in renal tissue damage and, ultimately, AKI. Mg replacement after Mg deficiency protects against CIS-induced AKI by decreasing CIS accumulation, increasing efflux transporter expression, inflammation, oxidative stress, and the activation of pathways that lead to kidney cell apoptosis/necrosis.