{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:53:46Z","timestamp":1784138026600,"version":"3.55.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:p> The molecular mechanisms of melamine-induced renal toxicity have not been fully understood. The purpose of the study aimed to investigate whether melamine and cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the kidney, which may contribute to abnormal water and sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg\u00b7kg body wt<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>), cyanuric acid (CA; 200 mg\u00b7kg body wt<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>), or Mel plus CA (Mel + CA; 100 mg\u00b7kg body wt<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, each) for 2 wk. Mel + CA caused damaged tubular epithelial structure and organelles, dilated tubular lumen, and inflammatory responses. Crystals were observed in urine and serum specimen, also in the lumen of dilated distal renal tubules. The combined ingestion of Mel and CA in rats caused a markedly impaired urinary concentration, which was associated with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla and \u03b1-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel + CA treatment was associated with increased protein expression of CD3 and mRNA levels of CD68 and F4\/80 as well as phosphorylation of NF-\u03baB in the kidney. Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1\u03b2 in the inner medulla of rats. NF-\u03baB inhibitor Bay 11-7082 reduced IL-1\u03b2 expression induced by Mel + CA and prevented downregulation of AQP2 in inner medullary collecting duct cell suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating defects and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney. <\/jats:p>","DOI":"10.1152\/ajprenal.00609.2017","type":"journal-article","created":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T13:54:20Z","timestamp":1522245260000},"page":"F199-F210","source":"Crossref","is-referenced-by-count":17,"title":["Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats"],"prefix":"10.1152","volume":"315","author":[{"given":"Feifei","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 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