Effect of Aminoglycoside Antibiotics on Cellular Functions of Kidney Epithelial Cell Line (LLC-PK₁): A Model System for Aminoglycoside Nephrotoxicity

¹ Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan
² Department of Biophysics, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, 606, Japan

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 cyclic AMP, with a correlation between the alteration of dome formation and cyclic AMP content. The specific activities of N-acetyl--d-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na⁺ + K⁺)-adenosine triphosphatase (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. Above results suggest that aminoglycoside toxicity to LLC-PK₁ cells may be similar to that reported for renal tubules.

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