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Evaluation of novel biomarkers of nephrotoxicity in rats co‐administered melamine and cyanuric acid
Author(s) -
Bandele Omari,
Camacho Luisa,
Ferguson Martine,
Reimschuessel Renate,
Stine Cynthia,
Black Thomas,
Olejnik Nicholas,
Keltner Zachary,
Scott Michael,
Da Costa Goncalo Gamboa,
Sprando Robert
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb592
Subject(s) - cyanuric acid , melamine , nephrotoxicity , creatinine , blood urea nitrogen , cystatin c , osteopontin , renal function , kidney , dosing , ingestion , medicine , urinary system , chemistry , toxicity , urology , pharmacology , organic chemistry
Although standard methods are used to detect impaired renal function, novel biomarkers have been identified that detect early changes in renal integrity. Recently, infants and pets experienced renal dysfunction after ingesting food tainted with melamine (MEL). Animal studies demonstrated that co‐ingestion of MEL and cyanuric acid (CYA) caused the formation of melamine‐cyanurate crystals that obstruct renal tubules. Using multiplexed ELISAs and RT‐PCR, we evaluated the ability of clusterin, KIM‐1, NGAL, osteopontin and TIMP‐1 to distinguish the effects of dosing schedule and matrix in rats gavaged with a 1:1 ratio of MEL and CYA either 45 min (staggered) or <1 min (consecutive) apart or dosed in feed. Due to treatment‐related nephrotoxic effects, animals in the staggered group were removed from the study on day 9. Compared to consecutive gavage and feed groups, urinary protein levels and gene expression for each biomarker in the staggered group were substantially elevated. The results were consistent with the treatment‐related effects on body and kidney weights, amount of melamine‐cyanurate crystals in renal tubules, and SCr and BUN levels in each treatment group. Our results demonstrate that the kidney biomarkers can detect the effects of compounds that block renal tubules and differentiate the effects of dosing schedule and matrix. Studies were funded by an interagency agreement between the FDA and the NIEHS.