Alterations of mitochondrial respiration induced by aminoglycoside antibiotics.

In vitro gentamicin treatment stimulates State 4 mitochondrial respiration and inhibits State 3 and DNP-uncoupled respiration. These effects are qualitatively similar in both hepatic and renal mitochondria. Threshold gentamicin concentrations for these effects were between 1 and 2 mM for renal mitochondria while hepatic mitochondria were slightly more sensitive. Neomycin, kanamycin, and streptomycin had effects qualitatively similar to those of gentamicin on State 4, State 3, and DNP-uncoupled respiration. The potency of the aminoglycosides in producing these effects strongly correlated with the number of ionizable amino groups present on the aminoglycoside molecule suggesting that cationic charge is an important molecular determinant of aminoglycoside-induced mitochondrial toxicity.