Renal Ultrastructural and Biochemical Injuries Induced by Aminoglycosides

• Published in: Environmental health perspectives 1984-08, Vol.57, p.293-299
• Main Authors: Cojocel, Constantin, Docius, N., Maita, Keizo, Smith, Jacqueline H., Hook, Jerry B.
• Format: Article
• Language: English
• Subjects: Absorption; Acetylglucosaminidase - metabolism; Aminoglycosides; Aminoglycosides - metabolism; Aminoglycosides - toxicity; Animals; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - toxicity; Biotransformation; Catabolism; Dosage; Enzymes; Excretion; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Kidney - drug effects; Kidney - metabolism; Kidney - ultrastructure; Kidney Tubules - metabolism; Kidneys; Low molecular weights; Lysosomes - metabolism; Male; Mechanisms of Cell Injury, April 10-15, 1984, Chicago, Illinois. FASEB Minisymposium, Federation of American Societies for Experimental Biology, 67th Annual Meeting; Muramidase - metabolism; Nephrotoxicity; Proteinuria - chemically induced; Rats; Sieving
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8457293

Aminoglycoside-induced proteinuria may result from general renal damage or may reflect alterations in specific steps in the renal handling of proteins. To differentiate between the two possibilities, experiments were designed to quantify the effects of nephrotoxic doses of gentamicin, tobramycin and netilmicin in the intact rat, isolated perfused rat kidney (IPK) and kidney slices using the cationic low molecular weight protein lysozyme as a model protein. Each aminoglycoside was administered IP to male Wistar rats (15 or 30 mg/kg/day) for 5 or 7 days. Scanning and transmission electron microscopy indicated that gentamicin and tobramycin induced a decrease in the number and diameter of endothelial fenestrae and degranulation of the myoepithelioid cells of the juxtaglomerular apparatus. Concurrently, gentamicin and tobramycin decreased the glomerular sieving coefficient of lysozyme from 0.8 to 0.6 and 0.5, respectively. Netilmicin did not affect the percentage reabsorption of lysozyme whereas gentamicin and tobramycin induced a 50% decrease in lysozyme reabsorption by the IPK. Gentamicin and tobramycin decreased equally lysozyme degradation by the IPK; this decrease was time- and dose-dependent when evaluated in slices from renal cortex. Perfusion of rat kidneys with gentamicin induced a dose-dependent decrease in reabsorption and catabolism of lysozyme. In conclusion, these studies demonstrate that polycationic aminoglycosides alter ultrastructure and glomerular permeability, tubular reabsorption and intracellular digestion of proteins.