Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats
•Multiplexed immunoassays were used to evaluate the effects of melamine or cyanuric acid in pregnant and non-pregnant rats.•Urinary renal biomarkers proved useful to detect kidney damage in rats prior to the loss of function.•This panel of biomarkers detected and differentiated the severity of adver...
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| Published in: | Food and chemical toxicology Vol. 74; pp. 301 - 308 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Oxford
Elsevier Ltd
01-12-2014
Elsevier |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | •Multiplexed immunoassays were used to evaluate the effects of melamine or cyanuric acid in pregnant and non-pregnant rats.•Urinary renal biomarkers proved useful to detect kidney damage in rats prior to the loss of function.•This panel of biomarkers detected and differentiated the severity of adverse effects induced by melamine or cyanuric acid.•Results indicated that pregnant rats were more sensitive to the nephrotoxic effects of melamine.•Our work further demonstrated urinary renal biomarkers as non-invasive indicators of early kidney damage.
Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0278-6915 1873-6351 |
| DOI: | 10.1016/j.fct.2014.10.013 |