Gentamicin-induced nephrotoxicity: A cell biology approach

Gentamicin is an antibiotic that exhibits a broad spectrum of activity and is particularly valuable in severe sepsis. Its use is, however, restricted because of the development of ototoxicity and nephrotoxicity (for the latter, see review in Ref. 1). At physiologic pH, the drug is highly charged and water soluble, and therefore it is practically unable to diffuse through biologic membranes.Nephrotoxicity has been related to a selective accumulation of gentamicin in the renal cortex [2, 3]. Morphologic lesions of proximal tubules have been documented in optic microscopy [4–6]. At the ultra-structural level, the earliest lesions observed concern the lysosomes, which show an accumulation of myeloid bodies [7–9].The mechanism of the gentamicin toxicity is, however, unknown. In this paper, we present studies on the localization of the drug at the cellular and subcellular levels, and on the enzymatic alterations that develop during gentamicin treatment