Time-restricted feeding schedules modify temporal variation of gentamicin experimental nephrotoxicity.
The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.
Beauchamp
D
D
Centre de Recherche en Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, and Département de Microbiologie, Faculté de Médecine, Sainte-Foy, Québec, Canada. denis.beauchamp@crchul.ulaval.ca
Guimont
C
C
Grenier
L
L
LeBrun
M
M
Tardif
D
D
Gourde
P
P
Bergeron
M G
MG
Thibault
L
L
Labrecque
G
G
D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002940:Circadian Rhythm / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005502:Food; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced*; D015999:Multivariate Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D005839:Gentamicins