Mechanism of ketotifen fumarate inhibiting renal calcium oxalate stone formation in SD rats

Abstract

Objectives: To investigate the inhibitory effect of ketotifen fumarate (KFA), a mast cell membrane stabilizer, on renal calcium oxalate stone (CaOx) formation and its possible molecular mechanism. Methods: We used the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for functional and pathway enrichment analyses of osteopontin (OPN), CD44 and fibronectin (FN). Blood biochemistry, reactive oxygen species ratio (ROS), mast cells, proteins (CD44, OPN and FN) and OPN receptor integrin family genes were detected by ELISA, flow cytometry, immunohistochemistry and RT-QPCR, respectively. Results: The crystal area of CaOx in the KFA and Control group was significantly smaller than that in the Model group. The number of activated mast cells, the expression levels of OPN and CD44 in the Control and KFA groups were significantly lower than those in the Model group, and the percentage of ROS in the KFA group was also significantly lower than that in the Model group. The mRNA expression levels of ITGB1, ITGA9, ITGAV and ITGA4 genes in the prominent OPN receptor integrin family increased significantly in the Model group. Conclusions: Ketotifen can effectively inhibit the crystal formation of CaOx and reduce the inflammatory response of tissue in SD rats. The mechanism may be to reduce the infiltration and activation of mast cells in renal tissue and down-regulate the expression of OPN, CD44 and FN in renal tubules and renal interstitium. And affect the synthesis of integrins (ITGA9, ITGA4, ITGAV, ITGB1, ITGB3 and ITGB5) and ROS.

Keywords

• Kidney calculi
• Ketotifen fumarate
• Mast cells
• Osteopontin
• CD44