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The aim of this study was to evaluate the protective effects of SeY (selenium-rich yeast) against Al (aluminum)-induced inflammation and ionic imbalances. Male Kunming mice were treated with Al (10 mg/kg) and/or SeY (0.1 mg/kg) by oral gavage for 28 days. The degree of inflammation was assessed by mRNA expression of inflammatory biomarkers. Ionic disorders were assessed by determining the Na + , K + , and Ca 2+ content, as well as the alteration in ATP-modifying enzymes (ATPases), including Na + K + -ATPase, Ca 2+ -ATPase, Mg 2+ -ATPase, Ca 2+ Mg 2+ -ATPase, and the mRNA levels of ATPase's subunits in kidney. It was observed here that SeY exhibited a significant protective effect on the kidney against the Al-induced upregulation of pro-inflammatory and downregulation of anti-inflammatory cytokines. Furthermore, a significant effect of Al on the Na + , K + , Ca 2+ , and Mg 2+ levels in kidney was observed, and Al was observed to decrease the activities of Na + K + -ATPase, Mg 2+ -ATPase, and Ca 2+ Mg 2+ -ATPase. The mRNA expression of the Na + K + -ATPase subunits and Ca 2+ -ATPase subunits was regulated significantly by Al. Notably, SeY modulated the Al-induced alterations of ion concentrations, ATPase activity, and mRNA expression of their subunits. These results suggest that SeY prevents renal toxicity caused by Al via regulation of inflammatory responses, ATPase activities, and transcription of their subunits.