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Hyperuricemia, hyperlipidemia and inflammation are associated with diabetic nephropathy. The NLRP3 inflammasome-mediated inflammation is recently recognized in the development of kidney injury. Urate and lipid are considered as danger signals in the NLRP3 inflammasome activation. Although dietary flavonoid quercetin and allopurinol alleviate hyperuricemia, dyslipidmia and inflammation, their nephroprotective effects are currently unknown. In this study, we used streptozotocin (STZ)-induced diabetic nephropathy model with hyperuricemia and dyslipidemia in rats, and found over-expression of renal inflammasome components NLRP3, apoptosis-associated speck-like protein and Caspase-1, resulting in elevation of IL-1β and IL-18, with subsequently deteriorated renal injury. These findings demonstrated the possible association between renal NLRP3 inflammasome activation and lipid accumulation to superimpose causes of nephrotoxicity in STZ-treated rats. The treatment of quercetin and allopurinol regulated renal urate transport-related proteins to reduce hyperuricemia, and lipid metabolism-related genes to alleviate kidney lipid accumulation in STZ-treated rats. Furthermore, quercetin and allopurinol were found to suppress renal NLRP3 inflammasome activation, at least partly, via their anti-hyperuricemic and anti-dyslipidemic effects, resulting in the amelioration of STZ-induced the superimposed nephrotoxicity in rats. These results may provide a basis for the prevention of diabetes-associated nephrotoxicity with urate-lowering agents such as quercetin and allopurinol.
Pubmed ID: 22701621
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View all literature mentionshis table shows the metadata and links to sources of the data and citations associated with the publicly available metagenome sequences used in the Dinsdale, Edwards, et al., analysis of 87 different metagenomes. The links will take you to the annotated sequences in the metagenomics SEED, CAMERA, and the NCBI Short Read Archve. Please note that all metagenomes are currently available to download via the ftp links, some are available in the meta-RAST, and other links will be added as soon as they become available. Citations for individual metagenomes will also be added as and when they become available. DNA sequences for all metagenomes are avaialble via anonymous FTP. Sponsor. This project was supported by the Gordon and Betty Moore Foundation Marine Microbial Initiative, National Science Foundation grants (F.R. and D.L.V.), a Department of Commerce ATP grant (F.R.), a National Research Initiative Competitive Grant from the USDA Cooperative State Research, Education and Extension Service (B.W.), the National Institute of Allergy and Infectious Diseases, the National Institutes of Health and the Department of Health and Human Services (R.S.).
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