TIME-RESTRICTED FEEDING SCHEDULES MODIFY TEMPORAL VARIATION OF GENTAMICIN EXPERIMENTAL NEPHROTOXICITY

The effect of timing of gentamicin dosing relative to food access peri ods was evaluated in experimental animals, Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/hg of body weigh t/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h accordi ng 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 subjecte d to a restricted feeding period, Results indicate that time-restricte d feeding schedules displace the peak and the trough of gentamicin-ind uced renal toxicity, as evaluated by changes in the inhibition of sphi ngomyelinase activity, cellular regeneration (incorporation of [H-3] t hymidine 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 gentamic in 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 ne phrotoxicity, The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephroto xicity than the light-dark cycle.