Identification of a subgroup of Sprague-Dawley rats highly sensitive to drug-induced renal toxicity.
Laboratory rats available from breeding facilities are usually assumed to be homogeneous populations within each strain; however, previous studies in our laboratory suggested that there may be a subgroup of Sprague-Dawley rats which are highly sensitive to aminoglycoside nephrotoxicity. The present study clearly identifies a subpopulation of Sprague-Dawley rats which was highly sensitive to nephrotoxicity from supratherapeutic doses (75 mg kg-1 day-1) of the aminoglycoside antibiotic gentamicin. Gentamicin was administered subcutaneously in a divided regimen, 25 mg/kg every 8 hr, for 7 days. Statistical analysis of post-treatment serum creatinine (SCR) and urea nitrogen (SUN) concentrations demonstrated two distinct populations: normally responding rats (SCR = 1.92 +/- 0.54 mg/dl, SUN = 71.5 +/- 18.4 mg/dl, N = 87) and highly sensitive rats (SCR = 4.10 +/- 0.83 mg/dl, SUN = 146.4 +/- 24.9 mg/dl, N = 12) (mean +/- SD). Comparison of predosing blood and serum chemistries between these two populations revealed statistical differences only in initial serum osmolality, oxygen tension, and total protein. Since there is a subpopulation of humans which are at risk for developing aminoglycoside nephrotoxicity due to unknown host factors, these highly sensitive Sprague-Dawley rats may provide an animal model for investigating this human clinical problem.
D000617:Aminoglycosides / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D003404:Creatinine / Q000097:blood; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D014508:Urea; D003404:Creatinine