Gentamicin aggravates renal injury by affecting mitochondrial dynamics, altering renal transporters expression, and exacerbating apoptosis.

Drug-induced nephrotoxicity has developed as a prevalent trigger in patients with hospital-acquired AKI. Gentamicin, a broad-spectrum bactericidal aminoglycoside antibiotic, is used clinically in synergy with other antibiotics. However, the presence of nephrotoxicity greatly limits their widespread clinical application. The kidney is one of the most energy intensive organs in the body, second to the heart in mitochondrial content and oxygen consumption. In particular, the mitochondria-rich proximal renal tubules are highly susceptible to be damaged by metabolic wastes or exogenous substances, and many studies have considered mitochondrial dysfunction as a targeted therapeutic strategy for the treatment of AKI. In this study, the results of in vitro experiments revealed that gentamicin could damage renal tubular epithelial cells in a dose- or time-dependent manner and resulted in impaired mitochondrial structure, decreased membrane potential, and reactive oxygen species (ROS) accumulation. Moreover, gentamicin aggravated renal injury by altering renal transporters expression, impairing mitochondrial homeostatic balance by affecting the expression of mitochondrial dynamics (e.g., OPA1, Mitofusin1/2, and DRP1), and promoting apoptosis through the Bax/Bcl2-Caspase3 pathway. It is worth noting that changes in serum creatinine or blood urea nitrogen (BUN) levels could not accurately identify early renal injury caused by gentamicin, and the road to finding an early diagnosis of kidney injury is still long. Our study provided a theoretical basis for gentamicin-induced renal injury and also contributed to the clinical application of gentamicin.