Antioxidants for Prevention of Gentamicin-induced Nephrotoxicity

Acute kidney injury (AKI) mainly develops following ischemic or toxic insults and is characterized by acute tubular injury and kidney dysfunction. However, pathogenesis of AKI is complex, and promoting events may be completely different, but similar pathways may be implicated in subsequent injury responses. To study AKI models, various methods were defined for each specific condition. Gentamicin, derived from gram-positive bacteria, has potential in treating aerobic gram-negative bacteria. Gentamicin has been extensively used for inducing AKI in experimental animals and evaluation of kidney protective agents, too. Accumulation of gentamicin in renal proximal tubule cells may trigger renal toxicity, which leads to brush border network injury. The renal toxicity involves kidneys free radical production and accretion, utilization of antioxidant defense mechanisms, and acute renal tubular cells necrosis, which leads to diminished glomerular filtration rate and kidney dysfunction. The pathological mechanisms also involve rise of endothelin-1, upregulation of transforming growth factor-β, augmentation of oxidative stress, significant increase in monocyte/macrophage infiltration into the renal cortex and medulla, apoptosis, and also necrosis. Gentamicin has also been shown to amplify the generation of superoxide anions, hydrogen peroxide, hydroxyl radicals, and reactive nitrogen species in the proximal tubular cells and lead to kidney damage.