Aminoglycosides have long been one of the commonest causes of drug-induced nephrotoxicity (137). Although a clear recognition of the patientand treatment-related risk factors (91), combined with the once-a-day schedule and effective monitoring procedures (98), have definitely improved the situation over what prevailed in the early 1980s (115), we are still short of having brought the safety of ...

Aminoglycosides are broad-spectrum antibacterial agents used in the treatment of urinary tract infections, tuberculosis, visceral leishmaniasis, sepsis newborns, as well cystic fibrosis. However, use aminoglycosides is limited due to their ototoxicity — risk developing serious adverse reactions, particular, persistent irreversible hearing loss and vestibular disorders associated with death hair...

RNA editing is an important co- and post-transcriptional event that generates RNA and protein diversity. Aminoglycosides are a group of bactericidal antibiotics and a mainstay of antimicrobial therapy for several life-threatening infections. However, aminoglycosides can induce ototoxicity, resulting in damage to the organs responsible for hearing and balance. At low concentrations, aminoglycosi...

The effects of aminoglycoside antibiotics on N-methyl-D-aspartate (NMDA) receptors were studied using voltage-clamp recording of recombinant NMDA receptors expressed in Xenopus oocytes. A number of aminoglycosides were found to potentiate macroscopic currents at heteromeric NR1A/NR2B receptors, but not at NR1A/NR2A, NR1A/NR2C, NR1A/NR2D, or NR1B/NR2B receptors. The degree of potentiation had a ...

Recent pharmacological studies have led to the hypothesis that aminoglycoside-induced ototoxicity is an excitotoxic process mediated, at least in part, by a polyamine-like modulation of N-methyl-D-aspartate (NMDA) receptors. To explore this hypothesis, we compared the effects of several aminoglycosides (neomycin B, kanamycin A, streptomycin, and dihydrostreptomycin) with spermine on recombinant...

To understand better the mechanisms of resistance-nodulation-division (RND)-type multidrug efflux pumps, we examined the Escherichia coli AcrD pump, whose typical substrates, aminoglycosides, are not expected to diffuse spontaneously across the lipid bilayer. The hexahistidine-tagged AcrD protein was purified and reconstituted into unilamellar proteoliposomes. Its activity was measured by the p...