Back to Search
Start Over
Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2018 Aug 01; Vol. 315 (2), pp. F199-F210. Date of Electronic Publication: 2018 Mar 28. - Publication Year :
- 2018
-
Abstract
- 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·kg body wt <superscript>-1</superscript> ·day <superscript>-1</superscript> ), cyanuric acid (CA; 200 mg·kg body wt <superscript>-1</superscript> ·day <superscript>-1</superscript> ), or Mel plus CA (Mel + CA; 100 mg·kg body wt <superscript>-1</superscript> ·day <superscript>-1</superscript> , 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 α-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-κB 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-1β in the inner medulla of rats. NF-κB inhibitor Bay 11-7082 reduced IL-1β 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.
- Subjects :
- Animals
Antigens, CD genetics
Antigens, CD metabolism
Antigens, Differentiation genetics
Antigens, Differentiation metabolism
Antigens, Differentiation, Myelomonocytic genetics
Antigens, Differentiation, Myelomonocytic metabolism
Aquaporins metabolism
CARD Signaling Adaptor Proteins metabolism
CD3 Complex metabolism
Caspase 1 metabolism
Interleukin-1beta metabolism
Kidney pathology
Kidney physiopathology
Kidney Concentrating Ability
Male
NF-kappa B metabolism
Phosphorylation
Polyuria chemically induced
Polyuria pathology
Polyuria physiopathology
Rats, Wistar
Signal Transduction
Sodium-Potassium-Chloride Symporters metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Inflammasomes metabolism
Kidney metabolism
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Polyuria metabolism
Triazines
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 315
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29592526
- Full Text :
- https://doi.org/10.1152/ajprenal.00609.2017