Circadian variations in the renal toxicity of gentamicin in rats

Toxicol Lett. 1988 Feb;40(2):175-82. doi: 10.1016/0378-4274(88)90159-2.


The hypothesis that sublethal doses of aminoglycosides cause renal tubule disorders resulting in changes of urine enzyme levels was investigated. The renal status following injection of a single sublethal dose of gentamicin (200 mg/kg) at different times during a 24 h cycle was studied. Increased excretion of gamma-glutamyl transferase, alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, used clinically as markers for tubule toxicity of aminoglycosides, was maximal when gentamicin was administered to rats at 2 p.m. and was minimal when injected at 8 p.m. These significant differences in enzyme excretion as a function of injection time are correlated with the concentration of gentamicin in the urine and in the renal cortex.

MeSH terms

  • Acetylglucosaminidase / urine
  • Aminopeptidases / urine
  • Animals
  • CD13 Antigens
  • Circadian Rhythm*
  • Dose-Response Relationship, Drug
  • Gentamicins / toxicity*
  • Kidney / drug effects*
  • Kidney Cortex / drug effects
  • Kidney Tubules / drug effects
  • Male
  • Rats
  • Rats, Inbred Strains
  • gamma-Glutamyltransferase / urine


  • Gentamicins
  • gamma-Glutamyltransferase
  • Acetylglucosaminidase
  • Aminopeptidases
  • CD13 Antigens