RENAL DAMAGE CAUSED BY GENTAMICIN - A STUDY OF THE EFFECT IN-VITRO USING ISOLATED RAT PROXIMAL TUBULAR FRAGMENTS

The clinical use of gentamicin (G) is limited because of its nephrotox ic potential. The administration of G (50 mg/kg) to rats in a 10-day d aily treatment gave a biphasic pattern of lactate dehydrogenase (LDH) and N-acetyl-beta-D-glucosaminidase (NAG) excretion. Alkaline phosphat ase (ALP) was highly elevated during the corresponding second phase wh ile a slight and statistically insignificant increase in glutamate deh ydrogenase (GDH) was obtained. The kidneys of such rats were isolated and tubules prepared and incubated for a specific period of time at 37 degrees C in Kreb's Henseleit bicarbonate buffer, pH 7.4. Results ind icate a considerable loss of protein (P < 0.01) after the 3rd and 10th days of treatment with G, elevated and significant increase of ALP af ter the Ist (P < 0.05) and 3rd (P < 0.01) days and significant increas e (P < 0.05) of GDH after the 10th day of treatment. The release of GD H, LDH and NAG from tubules of rats after a single dose of G was lower than the control rats while other treatments produced a significant i ncrease in ALP, LDH and NAG over the period of incubation. In vitro in cubation of tubules in the presence of several concentrations (5, 50, 500, 5000 mu g/g of wet cortex) of G indicated a time-dependent leakag e of enzyme only at the highest concentration of G. Our results clearl y indicate that cellular damage caused by G as evidenced by urinary en zyme excretion and marker enzyme release from isolated tubules occurs at very high concentration in vivo or in vitro and is time-dependent.