EFFECT OF AMINOGLYCOSIDE ANTIBIOTICS ON CELLULAR FUNCTIONS OF KIDNEY EPITHELIAL-CELL LINE (LLC-PK1) - A MODEL SYSTEM FOR AMINOGLYCOSIDE NEPHROTOXICITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (3) , 742-748
Abstract
The effects of aminoglycoside antibiotics on cellular functions of the LLC-PK1 kidney epithelial cell line were studied as a model system for aminoglycoside nephrotoxicity. The treatment with aminoglycoside antibiotics for 3 days caused a decrease in the dome number in the confluent LLC-PK1 cells and an increase in the floating cells in the culture medium. The inhibition of dome formation was dose-dependent and the rank-order of the degree of inhibition was compatible with the rank-order of in vivo nephrotoxicity. Aminoglycosides also decreased the intracellular content of cAMP, with a correlation between the alteration of dome formation and cAMP content. The specific activities of N-acetyl-.beta.-D-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na+ + K+)-ATP (marker for basolateral membranes) in the homogenate were decreased by gentamicin treatment. Lysosomal and apical membrane enzymes released into the culture medium were increased by gentamicin treatment. The ultrastructural alterations in the lysosomes of gentamicin-treated cells also were observed. Aminoglycoside toxicity to LLC-PK1 cells may be similar to that reported for renal tubules.