Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 decrease 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.
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PMID:Renal ultrastructural and biochemical injuries induced by aminoglycosides. 638 14

Gentamicin and other aminoglycoside antibiotics in high doses may produce proteinuria and other signs of nephrotoxicity. Proteinuria may result from general renal damage or may reflect alterations in specific steps in the renal handling of proteins. To distinguish between these two possibilities, experiments were designed to quantify the effects of nephrotoxic doses of several aminoglycosides on the renal handling of proteins in the isolated perfused rat kidney with the cationic low-molecular-weight protein lysozyme as a representative protein. Each aminoglycoside was administered ip to male Wistar rats (30 mg/kg/day) for 7 days. Lysozyme and 125I-lysozyme were added to the perfusate to achieve a lysozyme perfusate concentration of about 100 mg/liter. Clearances of inulin and lysozyme, release of tyrosine and trichloroacetic acid-soluble radioactive metabolites into the perfusate, and the glomerular sieving coefficient of lysozyme were determined. Scanning and transmission electron microscopy indicated that gentamicin and tobramycin decreased the number and diameter of the endothelial fenestrae of the glomerular capillaries. 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 decreased lysozyme reabsorption from 71.7 to 35.4 and 34.4% of the filtered load, respectively. Lysozyme degradation, estimated by the release of tyrosine into the perfusate during a 150-min perfusion period, was decreased from a control value of 12 mumol/liter to 4.43 and 4.65 mumol/liter in kidneys from rats treated with gentamicin and tobramycin, respectively. This study demonstrates that polycationic aminoglycosides may affect several processes involved in renal handling of lysozyme including glomerular permeability, tubular reabsorption, and intracellular proteolytic degradation.
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PMID:Effects of aminoglycosides on glomerular permeability, tubular reabsorption, and intracellular catabolism of the cationic low-molecular-weight protein lysozyme. 684 78