The relative nephrotoxicities of netilmicin (Sch 20569) and gentamicin were compared in rats at doses of 30, 60, 90, and 120 mg/kg per day for 15 days. Both drugs caused proteinuria and a decrease in urine osmolality; however, netilmicin produced significantly less changes at all doses than gentamicin. Whereas gentamicin resulted in a decline in creatinine clearance at all doses, netilmicin failed to cause a decline in creatinine clearance. Renal-cortical concentrations of antibiotic at sacrifice were similar in animals receiving either drug. Lightmicroscopic changes were less severe with netilmicin than gentamicin. Cytosegresomes with myeloid bodies were identified electron microscopically in the kidneys of animals receiving either netilmicin or gentamicin at all doses. Electron-microscopic manifestations were similar. The data indicate that in the rat, netilmicin is distinctly less nephrotoxic than gentamicin.Netilmicin (Sch 20569) is a new semisynthetic aminoglycoside which has in vitro bactericidal efficacy against both gentamicin-sensitive and gentamicin-resistant microorganisms (11). In vitro studies have shown that the spectrum of activity of netilmicin is similar to that of gentamicin against most gram-negative bacteria and Staphylococcus aureus. Although it has been shown to be active against many gentamicin-resistant organisms, it is somewhat less active than gentamicin against strains of Pseudomonas aeruginosa (12). In molecular structure, it closely resembles gentamicin C,a, MATERIALS AND METHODS Adult, male Sprague-Dawley rats weighing 200 to 225 g were selected, housed singly in metabolic cages, allowed free access to water, and fed a standard Purina rat diet ad libitum. The metabolic cages were equipped with screens below the animals' living space to avoid contamination of the urine specimens with feces or other debris. The design of the cages was such that the animals were unable to contaminate the specimens with drinking water. The 24-h urine samples were collected under mineral oil to preclude evaporation.Four groups of 24 rats each, half of which received netilmicin and half of which received gentamicin, were studied. Eight control animals which received saline diluent accompanied each of the four experimental groups. Groups 1, 2, 3, and 4 received the drugs subcutaneously in 1 ml of saline diluent at doses of 30, 60, 90, and 120 mg/kg per day, respectively. Urine specimens were collected on days 3, 5, 8, 10, 12, and 15, at which time urine volume, urine protein excretion, and urine osmolality were measured.Eight animals from each group, four receiving netilmicin and four receiving gentamicin, were sacrificed 24 h after a previous injection of antibiotic on days 5, 10, and 15. Four control animals for each group were sacrificed on days 5 and 15. Serum was collected for the measurement of urea nitrogen and creatinine clearance. The kidneys were removed and were examined by light and electron microscopy. In addition, homogenates were prepared for the measurement of antibiotic concentrations in ...
Providone-iodine is used as a topical antimicrobial in burn patients. Although absorption of iodine has been thought to be negligible, several patients have recently been noted with substantial elevations of serum free iodide. Unexplained abnormalities occurred in several of these patients, renal failure, metabolic acidosis, and elevation of serum glutamic oxaloacetic transaminase. It is conceivable that the large iodide loads noted were at least in part responsible for these abnormalities.
To assess their potential value as early indicators of gentamicin-induced kidney damage, lysosomal hydrolases were measured in the 24-h urines of rats receiving 30 or 60 mg of gentamicin per kg per day for 15 days. Proteinuria, urine osmolality, blood urea nitrogen, and creatinine clearance were also measured. Kidney tissue was examined by both light and electron microscopy. Beta-galactosidase, beta-n-acetyl-hexosaminidase, and alpha-fucosidase were sensitive indicators and were significantly elevated above control values by day 3 at both doses (P < 0.01). Proteinuria, urine osmolality, and tests reflecting glomerular filtration rate were later indicators of nephron damage. Changes by light microscopy were detected on day 5. Necrosis was most prominent in the proximal convoluted tubules on day 10. Electron microscopy revealed numerous cytosomes with myeloid bodies within the proximal tubular epithelium on day 5. Lysosomal enzymuria appears to be an early manifestation of gentamicin nephrotoxicity and may possibly be related to the lysosomal abnormalities seen on electron microscopy.
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