Ultrastructural changes of aminoglycosides on rats

ABSTRACT

Gentamicin, one of the aminoglycoside antibiotics, was administered intraperitoneally twice a day at a dose of 4 mg/kg body weight, a dose relevant to those used in the clinical practice. The kidney and liver were examined by light [semithin sections] and electron microscopy after 2, 7 and 14 days of treatment. Biochemical changes were also studied after the same periods and were found to be statistically insignificant even after 14 days. However, morphology of the liver and kidney, examined by light microscopy, was unchanged throughout the whole period of the study as compared with controls. The renal ultrastructural changes detected were dependent on the duration of drug administration and confined primary to the proximal tubule. Specific lysosomal alterations were detected as early as 2 days of treatment, these consisted of increased number of cytosegresomes, many of which contatined electron -dense multilamellar structures myeloid bodies. Alterations of the other subcellular structures were observed only after 7 and 14 days of treatment. the golgi apparatus became hypertrophied and the number of ribosomes were increased. Later, the mitochondria were affected giving the picture of megamitochondria. In addition, distal tubular cells showed marked vacuolization and disruption of the basal cell architecture. The most striktrig hepatic changes were prominent proliferation of perixosomes. prominent increase in smooth endoplasmic reticulum and a disruption of the rough endoplasmic reticulum. Thus these early ultrastructural alterations may indicate that therapeutic doses of gentamicin can induce renal and hepatic dysfunction in humans. This may be an important fact on limiting the clinical utility of gentamicin