Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials
| Autor: | Friedrich von Landenberg, Stephanie Czasch, Katharina Frick, Philip G. Hewitt, Barbara Emde, Tobias Christian Fuchs |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Antimetabolites Antineoplastic Urinary system Drug Evaluation Preclinical Pharmacology Toxicology Pathology and Forensic Medicine Nephrotoxicity Xenobiotics Vancomycin Medicine Animals Rats Wistar Molecular Biology Cisplatin Kidney Clusterin biology Dose-Response Relationship Drug business.industry Cell Biology Dipstick Anti-Bacterial Agents Rats medicine.anatomical_structure Toxicity Tests Subacute Toxicity Acute Disease biology.protein Biomarker (medicine) Female Kidney Diseases Puromycin business Biomarkers medicine.drug |
| Zdroj: | Toxicologic pathology. 40(7) |
| ISSN: | 1533-1601 |
| Popis: | Novel urinary protein biomarkers for the detection of acute renal damage, recently accepted by the U.S. Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be validated in practice. Limited data regarding the performance of these acute markers after subacute or subchronic treatment are publicly available. To increase the area of applicability of these markers, it is important to evaluate the ability to detect them after 28 days of treatment or even longer. Wistar rats were treated with three doses of cisplatin, vancomycin, or puromycin to induce renal damage. Twelve candidate proteins were measured by Luminex xMAP–based WideScreen assays, MesoScale Discovery–based MULTI-SPOT technology, or RENA-strip dipstick assay after 28 days. Treatment with all three model compounds resulted in a dose-dependent increase in urinary biomarkers, specific for the observed areas within the nephron, determined histopathologically. The most promising biomarkers in this study were NGAL, Kim-1, osteopontin, clusterin, RPA-1, and GSTYb1, detected by multiplexing technologies. The RENA-strip dipstick assay delivered good diagnostic results for vancomycin-treated but not for cisplatin- or puromycin-treated rats. Taken together, the data show that these new biomarkers are robust and measurable for longer term studies to predict different types of kidney toxicities. |
| Databáze: | OpenAIRE |
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