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 nephrotoxic potential. The administration of G (50 mg/kg) to rats in a 10-day daily treatment gave a biphasic pattern of lactate dehydrogenase (LDH) and N-acetyl-beta-D-glucosaminidase (NAG) excretion. Alkaline phosphatase (ALP) was highly elevated during the corresponding second phase while a slight and statistically insignificant increase in glutamate dehydrogenase (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 indicate a considerable loss of protein (P < 0.01) after the 3rd and 10th days of treatment with G, elevated and significant increase of ALP after the 1st (P < 0.05) and 3rd (P < 0.01) days and significant increase (P < 0.05) of GDH after the 10th day of treatment. The release of GDH, 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 increase in ALP, LDH and NAG over the period of incubation. In vitro incubation of tubules in the presence of several concentrations (5, 50, 500, 5000 micrograms/g of wet cortex) of G indicated a time-dependent leakage of enzyme only at the highest concentration of G. Our results clearly indicate that cellular damage caused by G as evidenced by urinary enzyme excretion and marker enzyme release from isolated tubules occurs at very high concentration in vivo or in vitro and is time-dependent.
Obatomi
D K
DK
Department of Biochemistry, King's College London, UK.
Plummer
D T
DT
D000118:Acetylglucosaminidase / Q000652:urine; D000469:Alkaline Phosphatase / Q000652:urine; D000818:Animals; D005839:Gentamicins / Q000633:toxicity*; D005969:Glutamate Dehydrogenase / Q000652:urine; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology*; D007770:L-Lactate Dehydrogenase / Q000652:urine; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D005839:Gentamicins; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D000469:Alkaline Phosphatase; D000118:Acetylglucosaminidase