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© 1986 Oxford University Press

research-article

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitive to Drug-Induced Renal Toxicity

J. EDMOND RIVIERE1, LYNN P. Dix, MICHAEL P. CARVER and DONITA L. FRAZIER

Laboratory of Toxicokinetics, School of Veterinary Medicine Interdepartmental Toxicology Program, North Carolina Slate University Raleigh, North Carolina 27606

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitive to Drug-Induced Renal Toxicity. RIVIERE, J. E., DIX, L. P., CARVER, M. P., AND FRAZIER, D. L. (1986). Fundam. Appl. Toxicol. 7, 126-131. 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 subcu-taneously 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.


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