Harrill2: Drug study: Survey of kidney injury due to DB289 treatment in females of 34 inbred strains of mice (2012)

Harrill AH, Desmet KD, Wolf KK, Bridges AS, Eaddy JS, Kurtz CL, Hall JE, Paine MF, Tidwell RR, Watkins PB. A Mouse Diversity Panel Approach Reveals the Potential for Clinical Kidney Injury Due to DB289 Not Predicted by Classical Rodent Models. Toxicol Sci. 2012 Dec;130(2):416-26. doi: 10.1093/toxsci/kfs238. Epub 2012 Aug 31.   PubMed 22940726     FullText

"Difference" measurements were computed by MPD from the strain means (fold change, D289 over control) and are available for download in a separate supplementary file.

MPD curation note: DB289 was previously tested in clinical trials to treat African trypanosomiasis. However, the trial was terminated when subjects developed severe kidney injury, an effect not predicted from preclinical testing. This project (Harrill2) highlights the utility of inbred strains to predict clinically relevant toxicities to drugs prior to clinical trials.

Harrill2 downloads
• Download Harrill2 project data set     one row per animal, one column per trait
• Download Harrill2 strain means, SD, N, etc.     one row per strain/sex/measure
• Harrill2 supplementary data
Participants Alison Harrill       University of Arkansas for Medical Sciences Little Rock, AR
ContactAlison Harrill     AHHarrill@uams.edu     Lab web site
AcknowledgementsFunding provided by the Bill and Melinda Gates Foundation.
Project type Phenotype strain survey data set
MPD identifiersHarrill2     MPD:441
Data changelog No updates/corrections.       Initial release date: 12/2012.
Formatted citation
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Mice received ten days of oral treatment with DB289 (pafuramidine) or vehicle. Blood chemistry and urinalysis were performed. Urine biomarkers of kidney injury were measured and organs weighed.

Summary of procedures that were conducted
• body weight DB289-treated vs. control.
• metabolic panel Blood urea nitrogen, alanine transaminase, creatinine. DB289-treated vs. control.
• urinalysis Urine volume, creatinine. DB289-treated vs. control.
• biomarker quantification Kidney injury molecule 1 (KIM-1). DB289-treated vs. control.
• organ weights Kidney and liver weights. DB289-treated vs. control.
• drug and metabolite quantification Kidney metabolite (DB75) concentration. DB289-treated vs. control.
Mice: inbred   34 strains   ♀   age 6-8wks   2 cohorts