Acute kidney inury induced by melamine and cyanuric acid in rats
2011
Hochschulschrift
Zugriff:
99
Melamine is an industrial chemical used for thermosetting plastic production. In 2008, melamine-adulterated infant milk formula from China led to the development of kidney stones and acute kidney failure in many infants worldwide. Cyanuric acid (CA), an industrial byproduct of melamine, is also frequently present in melamine-adulterated food. Clinical studies indicated that melamine severely affects the kidneys of children, but rarely harms adults. There is limited research on the mechanism of melamine-induced renal injury. Melamine-contaminated pet food from China was also a serious problem, and necropsies of the dead pets indicated renal injury, with inflammatory cells surrounding crystal-containing renal tubules. In the present study, we investigated the effect of melamine alone, CA alone, and melamine and CA together on acute kidney injury (AKI) and the role of macrophage activation in 3-week-old (3wks) and 8-week-old (8wks) male Sprague-Dawley rats. Three-week-old (70-80 g) and 8-week-old (250-300 g) rats were allocated to 9 dietary groups for three days: carboxymethyl cellulose (vehicle), melamine (100 or 200 mg/kg BW), CA (100 or 200 mg/kg BW) and melamine and CA (10, 30, 50 and 100 mg/kg BW). In rats fed melamine alone or CA alone, there were no changes in serum blood urea nitrogen (BUN) and creatinine, and no renal crystals formed. However, in rats fed melamine and CA (100 mg/kg BW) together there were significant increases in BUN and creatinine, crystals in the renal medulla, interstitial inflammation, and tubular injury. The 3wks had more severe renal injury, inflammation, and increase of macrophages than 8wks. Based on real time PCR and western blotting experiments, melamine/CA increased the expression of proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1]) and a macrophage M1 marker (inducible nitric oxide synthase) in 3wks; melamine/CA increased the expression of arginase-1 (Arg-1) and IL-10 in 8wks. A study of the time course of melamine/CA-induced renal injury in 3wks indicated significant increases of BUN, serum creatinine, tubulointerstitial injury score, and expression of proinflammatory cytokines at day 3. In contrast, 8wks had higher expressions of IL-10 and macrophage M2 marker of Arg-1 at day 1. In conclusion, simultaneous administration of melamine and CA leads to renal medullar crystals and renal injury in rats. Three-week-old rats experienced more severe kidney damage and inflammation than 8wks. This may be because melamine/CA increases M1 macrophage activation in 3wks, leading to tissue injury, whereas melamine/CA increases M2 macrophage activation in 8wks, leading to tissue repair. Melamine/CA-related AKI may be caused by mechanical injury of renal tubular crystals, macrophage-related inflammation, or both.
Titel: |
Acute kidney inury induced by melamine and cyanuric acid in rats
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Autor/in / Beteiligte Person: | Yang, Wen-Ying ; 楊汶英 |
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Veröffentlichung: | 2011 |
Medientyp: | Hochschulschrift |
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