Oxidant mechanisms in gentamicin nephrotoxicity.
Acute renal failure is a major complication of aminoglycoside antibiotics, which are widely used in the treatment of gram-negative infections. Sequential reduction of oxygen along the univalent pathway leads to the generation of superoxide anion, hydrogen peroxide, hydroxyl radical, and water. A large body of in vitro and in vivo evidence indicates that these partially reduced oxygen metabolites are important mediators of gentamicin nephrotoxicity. Gentamicin has been shown to enhance the generation of superoxide anion and hydrogen peroxide by renal cortical mitochondria. The interaction between superoxide anion and hydrogen peroxide in the presence of metal catalyst can lead to the generation of hydroxyl radical. Gentamicin has been shown to lead to release of iron from renal cortical mitochondria and to enhance generation of hydroxyl radical. These in vitro observations have been supported by in vivo studies in which scavengers of reactive oxygen metabolites and iron chelators have shown to be protective in gentamicin induced acute renal failure. There is evidence to suggest that studies may have broader implication in being relevant to other aminoglycosides including streptomycin and being applicable to other major toxicity of aminoglycoside such as ototoxicity.
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
P D
PD
Walker
Y
Y
Barri
S V
SV
Shah
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D005609:Free Radicals; D005839:Gentamicins / Q000009:adverse effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005609:Free Radicals; D005839:Gentamicins; D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide; D007501:Iron