Insights Into Regulated Cell Death Pathways in Gentamicin‐Induced Nephrotoxicity: Molecular Mechanisms and Future Perspectives

Acute kidney injury (AKI) induced by medication-related toxicity is a significant health concern in contemporary healthcare systems. Gentamicin, a potent aminoglycoside antibiotic crucial for managing serious Gram-negative bacterial infections, is a prominent risk factor due to its accumulation in the renal cortex, which often leads to renal toxicity. In addition to direct tubular damage from selective uptake of gentamicin by the megalin/cubilin receptor complex, intrinsic signaling pathways associated with gentamicin-induced AKI, including lysosomal rupture, mitochondrial dysfunction, and reactive oxygen species production, exacerbate the development and severity of the condition. The mechanisms underlying and preventing gentamicin-induced nephrotoxicity remain poorly understood, despite extensive research. Recent developments in regulated cell death (RCD) offer novel insights. This review seeks to clarify the growing significance and fundamental molecular mechanisms of RCD pathways in gentamicin-induced AKI. A better understanding of the mechanisms governing cell death in gentamicin-induced nephrotoxicity may facilitate the development of effective therapeutic options.