The effect of gentamicin on human renal proximal tubular cells

Human renal proximal tubular cells were exposed to gentamicin (0, 0.1, 0.5, 1.0, 5.0, 10.0 mg/ml medium) for 3, 7, 10, and 14 days. Cells were counted and cell viability was estimated by lactate dehydrogenase release. In addition, brush border-associated (gamma-glutamyltransferase) and lysosomal (acid phosphatase, N-acetyl-beta-glucosaminidase, and sphingomyelinase) enzyme activities were measured (0.01, 1.0, 3.3 mg/ml gentamicin for 3, 7, 10 and 14 days). The number of cells did not change significantly after gentamicin treatment. Cell viability, however, significantly decreased after 3 and 7 days exposure to 5 and 10 mg/ml gentamicin. Total lactate dehydrogenase activity was significantly decreased at 7, 10, and 14 days exposure to gentamicin greater than or equal to 5.0 mg/ml. gamma-Glutamyltransferase, acid phosphatase, and sphingomyelinase were decreased at 3, 7, and 10 days exposure to gentamicin greater than or equal to 1.0 mg/ml. Continued exposure to gentamicin less than or equal to 1.0 mg/ml appeared to have little or no effect on the activity of these enzymes at 14 days. N-Acetyl-beta-glucosaminidase activity, in contrast, was elevated (120-140% control) in the gentamicin-treated (greater than or equal to 1.0 mg/ml) groups at all time periods studied. Thus, gentamicin exposure resulted in changes in some of the enzyme activities in human renal proximal tubular cell cultures, but longer exposure (14 days) to gentamicin (less than or equal to 1.0 mg/ml) resulted in a return to control levels of some activities.