1. Effects of the xanthine oxidase inhibitor, febuxostat, on the expression of monocyte chemoattractant protein-1 and synchronous genes in MDCK cells treated with calcium oxalate monohydrate crystals
- Author
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Shinya Inoue, Yusuke Nakazawa, Yuka Nakamura, Katsuhito Miyazawa, Takanori Tatsuno, Yasuhito Ishigaki, and Dan Nakai
- Subjects
Chemokine ,Xanthine Oxidase ,medicine.drug_class ,Urology ,030232 urology & nephrology ,Calcium oxalate ,Kidney ,Madin Darby Canine Kidney Cells ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dogs ,Febuxostat ,Gene expression ,medicine ,Animals ,Xanthine oxidase ,Xanthine oxidase inhibitor ,Chemokine CCL2 ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Calcium Oxalate ,business.industry ,Monocyte ,medicine.anatomical_structure ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,biology.protein ,business ,medicine.drug - Abstract
Objectives To examine the effects of the selective xanthine oxidase inhibitor febuxostat on the expression of inflammation-related genes involved in stone formation. Methods Madin-Darby canine kidney cells were exposed to febuxostat, followed by calcium oxalate monohydrate crystals. Monocyte chemoattractant protein-1 messenger ribonucleic acid expression levels were determined by real-time reverse transcription polymerase chain reaction analysis. Deoxyribonucleic acid microarray analysis was utilized to evaluate gene expression. Results Calcium oxalate monohydrate crystals activated monocyte chemoattractant protein-1 messenger ribonucleic acid expression in a time- and concentration-dependent manner. Febuxostat suppressed monocyte chemoattractant protein-1 expression. The expression levels of a group of inflammatory genes, including interleukin-8 and chemokine (C-X-C motif) ligand 10, which are downstream of reactive oxygen species, fluctuated similarly to the observed monocyte chemoattractant protein-1 fluctuations and were reduced by febuxostat pretreatment. Conclusions Febuxostat exerts preventive effects against reactive oxygen species production and oxidative stress, and might represent a potential treatment for calcium oxalate stones. In the present study, febuxostat downregulated the calcium oxalate monohydrate crystal-induced monocyte chemoattractant protein-1 messenger ribonucleic acid expression.
- Published
- 2020