Age-dependent gentamicin experimental nephrotoxicity.
The nephrotoxic potential of gentamicin was compared in adult (2-month-old) and old (24-month-old) female Sprague-Dawley rats in a model of short-term infusion. Animals were infused over a 12-hr period with saline or with gentamicin achieving steady-state serum levels of 56.1 +/- 11.7 (n = 18) and 59.8 +/- 14.7 (n = 17) micrograms/ml +/- S.D. (N.S.) in the adult and the old rats, respectively. Animals were sacrificed 2 hr (day 0), 4 days and 8 days after the end of the infusion. The renal cortical levels of gentamicin at day 0 (2 hr after the end of the infusion) were 1161 +/- 120 and 1125 +/- 275 micrograms/g of tissue +/- S.D. (N.S.) in the adult and the old rats, respectively. Tissue levels of gentamicin were lower in both gentamicin-treated groups on day 4 and 8 as compared with day 0 (P less than .05). The sphingomyelinase activity (measure of the lysosomal phospholipidosis) was significantly inhibited in the renal cortex of the adult and the old rats, but no significant difference was observed between these two groups. The in vivo [3H]thymidine incorporation into DNA, expressed as the percentage of the values measured in each age-matched control group, was significantly lower in the old animals as compared with that measured in the adult rats (P less than .05). No significant difference was observed in the renal function of adult rats, but a significant increase in the serum creatinine levels was measured in the old rats on day 4 of the experiment (248% of the control value, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Beauchamp
D
D
Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
Gourde
P
P
Thériault
G
G
Bergeron
M G
MG
D000367:Age Factors; D000818:Animals; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000378:metabolism; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D005839:Gentamicins; D004247:DNA; D003404:Creatinine; D013108:Sphingomyelin Phosphodiesterase; D013936:Thymidine