Melamine promotes calcium crystal formation in three-dimensional microfluidic device

Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an induc...

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Published inScientific reports Vol. 9; no. 1; pp. 875 - 14
Main Authors Gombedza, Farai, Evans, Sade, Shin, Samuel, Awuah Boadi, Eugenia, Zhang, Qian, Nie, Zhihong, Bandyopadhyay, Bidhan C.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 29.01.2019
Nature Publishing Group
Nature Portfolio
Subjects
13
13/62
14
14/63
631/1647/277
639/925/928/1069
692/499
Calcium oxalate
Calcium phosphates
Crystallization
Crystals
Humanities and Social Sciences
Kidney stones
Microenvironments
Microfluidics
multidisciplinary
Oxalic acid
Science
Science (multidisciplinary)
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Summary:Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP + CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and/or CaOx crystal formation ex-vivo will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-37191-5