EXPERIMENTAL STUDIES ON THE NEPHROTOXICITY OF AMINOGLYCOSIDE ANTIBIOTICS IN RATS

I. DRUG INCORPORATION INTO THE RENAL CORTICAL CELLS AND THE INHIBITION OF PROTEIN BIOSYNTHESIS

Abstract

Distribution of aminoglycoside antibiotics in the renal cells was examined at the subcellular level using tritium labeled kanamycin and dibekacin. Inhibition of protein biosynthesis within the renal cortex was suggested, as the result, by these antibiotic agents, and the result of the examination of protein biosynthesis is also reported:
1. Aminoglycoside antibiotics were incorporated in the renal cortex in rats, and accumulated there.
2. They were distributed in high concentration in the rough microsome fraction in the renal cortex, particularly in the ribosome, and the accumulation was notable even after 24 hours of the administration.
3. Similar combination of aminoglycoside antibiotics and ribosome was observed in in vitro experiment, and they combined with ribosome in the liver and kidney firmly in the same degree, and no organ specificity was observed.
4. Ratio of RNA in the submicrosome fractions and aminoglycoside antibiotics was a constant in any fractions, suggesting that the antibiotics combine with RNA rather than protein.
5. In pretreated rats with aminoglycoside antibiotics, incorporation of ³H-leucine was suppressed, and the suppression was antibiotics concentration dependent.
6. Inhibition of ³H-leucine incorporation was not shown in the liver of kanamycin administered rats, and concentration difference of kanamycin in various organs was notable.
7. In vitro experiments of protein biosynthesis in the renal cortex ribosome in rats showed that effect of protein biosynthesis inhibition was nearly proportional to the renal toxicity of antibiotics, and the degree of inhibition was in the order of dibekacin, gentamicin, netilmicin and kanamycin.