Nephrotoxicity of low doses of tobramycin in rats: effect of the time of administration.
The circadian and the circannual variations of the nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats. Animals were maintained on a light-dark period of 14/10 hrs (light on: 06h00 to 20h00). They were injected once daily for 4 and 10 days with saline or tobramycin at a dose of 40 mg/kg/day i.p. at either 08h00, 14h00, 20h00 and 02h00, in April 1991, July 91, October 91, January 92. In April 91, tobramycin injected at 14h00 during 10 days induced a significant increase of [3H]-thymidine incorporation into DNA of renal cortex as compared to other groups (p < 0.01): toxicity was highest at 14h00 and lowest at 02h00. No temporal change was observed in the renal cortical accumulation of tobramycin, and in serum creatinine after the 4 or 10 days of treatment. In experiments done in April, July and October 1991 and in January 1992, no circannual variation was found in tobramycin cortical levels but peaks of toxicity were observed at 02h00 in April and October 1991 and at 14h00 in July 1991 and January 1992. There was no linear correlation between the toxicity and the tobramycin accumulation in the renal cortex (r = 0.21). The data suggest that the circadian changes in tobramycin toxicity are due to temporal changes in the susceptibility of renal cells to tobramycin.
Lin
L
L
Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Grenier
L
L
Thériault
G
G
Gourde
P
P
Yoshiyama
Y
Y
Bergeron
M G
MG
Labrecque
G
G
Beauchamp
D
D
D000818:Animals; D002940:Circadian Rhythm; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D012621:Seasons; D013997:Time Factors; D014031:Tobramycin / Q000493:pharmacokinetics / Q000633:toxicity*
D004247:DNA; D003404:Creatinine; D014031:Tobramycin