Effect of gentamicin treatment on glutamine and lactate metabolism by the renal cortex of the rat.
The present study was performed to measure the uptake of main renal cortical fuel substrates (glutamine and lactate) and the release of the main renal cortical products (ammonia and glucose) by cortical slices from gentamicin-treated rats. Experiments were done in 2 groups of female Wistar rats (250 g): In gentamicin group (n = 13), rats were injected s.c. with gentamicin-sulphate 100 mg/Kg body wt/day for 5 days. Control rats (n = 13) received isotonic saline. After anesthesia and blood sampling, renal cortical slices were obtained and incubated with L-glutamine and/or lactate at 1 or 5 mM concentration, containing L-glutamate and/or pyruvate at 0.1 or 0.5 mM. Creatinine clearance was reduced to a 50% in gentamicin-treated rats. In addition these animals showed a sharp increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and alkaline phosphatase. Light microscopy examination revealed extensive cell necrosis and tubular obstruction of the proximal tubules in kidneys of rats injected with gentamicin. The renal cortical gentamicin concentration of rats injected with gentamicin was 310 +/- 43 mu/g, whereas it was undetectable in control rats. Cortical slices from gentamicin-treated rats, compared to control ones, showed a reduced production of ammonia and glucose, without differences in glutamine or lactate extraction. These alterations can be explained by both the increased rate of anabolic reactions to recover cell damage associated to renal failure, as well as by a direct effect of gentamicin on the rate of carboxylation reactions.
Rivas-Cabañero
L
L
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
García-Bastos
J L
JL
Arevalo
M
M
Rodríguez-Barbero
A
A
López-Novoa
J M
JM
D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D051381:Rats; D017208:Rats, Wistar
D005839:Gentamicins; D007773:Lactates; D005973:Glutamine; D019344:Lactic Acid; D000641:Ammonia; D005947:Glucose