alexa Feasibility of Protein Biomarkers in the Prediction of Subclinical Doxorubicin Nephrotoxicity in Male Sprague-Dawley Rat

Journal of Molecular Biomarkers & Diagnosis
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Research Article

Feasibility of Protein Biomarkers in the Prediction of Subclinical Doxorubicin Nephrotoxicity in Male Sprague-Dawley Rat

James Eric McDuffie1*, Manisha Sonee2, Jing Ma1, Frederic Almy2, Xuejun Liu3, David La1 and Sandra Snook1

1Discovery Sciences, Janssen Research & Development, L.L.C., San Diego, CA, USA

2Discovery Sciences, Janssen Research & Development, L.L.C., Spring House, PA, USA

3Immunology Biomarkers, Janssen Research & Development, L.L.C., San Diego, CA, USA

*Corresponding Author:
James Eric McDuffie
Janssen Research & Development
L.L.C., 3210 Merryfield Row
San Diego, CA 92121, USA
Tel: 858 320 3463
Fax: 858-784-3242
E-mail: [email protected]

Received Date: December 19, 2013; Accepted Date: January 16, 2014; Published Date: January 22, 2014

Citation: McDuffie JE, Sonee M, Ma J, Almy F, Liu X, et al. (2014) Feasibility of Protein Biomarkers in the Prediction of Subclinical Doxorubicin Nephrotoxicity in Male Sprague-Dawley Rat. J Mol Biomark Diagn 5:165. doi:10.4172/2155-9929.1000165

Copyright: © 2014 McDuffie JE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited



The feasibility of proteinbiomarkers in the prediction of subclinical doxorubicin nephrotoxicity was evaluated in male Sprague-Dawley rats during a 2-week study with once‑weekly dosing. Doxorubicin (5, 7.5, and 10 mg/kg/ dose) or 0.9% Saline was intravenously administered on days 1 and 8. Urine and serum were collected at various time points. Surviving animals were euthanized on day 14, and tissues were collected for microscopic examination. Severe clinical signs were observed in the 7.5 and 10 mg/kg/dose groups. Biomarker data are not reported for these groups because the objective of this study was to evaluate biomarkers at doses not associated with clinical signs. In the 5 mg/kg group, increased serum concentrations of urea nitrogen were observed on day 14 with concurrent renal histopathology findings which were primarily characterized as slight renal glomerular and tubular injury with mild multi-focal intratubular hyaline casts consistent with protein leakage from damaged glomeruli. Of the various urinary protein biomarkers examined, increased urinary concentrations of albumin was observed on day 7 and increased total protein, albumin and lipocalin‑2 were observed on day 14. Taken together, these findings showed that urinary albumin was more sensitive and selective than urinary total protein, lipocalin-2, kidney injury molecule 1 and/or osteopontin in the prediction of progressive doxorubicin‑induced glomerular toxicity with secondary renal tubular toxicity in male Sprague‑Dawley rats.

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