Gentamicin nephrotoxicity in rats. I. Acute biochemical and ultrastructural effects
Vera-Roman, J.; Krishnakantha, T.P.; Cuppage, F.E.
Laboratory Investigation; A Journal of Technical Methods and Pathology 33(4): 412-417
1975
ISSN/ISBN: 0023-6837 PMID: 1186122 Document Number: 84400
This investigation characterizes the acute biochemical and ultrastructural alterations within the rat kidney following the single injection of 10, 40, 80, or 160 mg of gentamicin per kg of rat weight. Gentamicin was given i/p and rats were killed 80 minutes later. To assess a possible inhibitory effect upon protein synthesis 3H-leucine was injected 20 minutes after the antibiotic and renal cortex was assayed for whole tissue and the protein fraction amino acid uptake. To exclude the possibility of gentamicin-induced lysosomal membrane instability with subsequent release of acid hydrolases, the activity of acid phosphatase was assayed in the supernatant and the residue of cortical homogenates containing the lysosomal fraction. Ultrastructural changes were concomitantly studied. To determine the intracellular localization of gentamicin, levels of the antibiotic were measured in subcellular fractions of cortical homogenates obtained from rats 2 hours after a single s/c injection of 20 mg of gentamicin per kg of rat weight. No gentamicin-induced alterations either of protein synthesis or of acid phosphatase distribution were demonstrated. Ultrastructural changes were most marked at 160 mg/kg, consisting mainly of dilation of the endoplasmic reticulum, altered mitochondria, and increased cytosegresomes. Significant quantities of gentamicin were distributed within the nuclear, mitochondrial, and microsomal fractions. These studies indicate that although cytoplasmic alterations are prominent within the proximal tubular epithelial cells, they are not likely the result of either inhibition of protein synthesis or release of acid phosphatase from lysosomes.