%0 Journal Article %A Wanghui Jing %A Ane Nunes %A Ted Farzaneh %A Mahyar Khazaeli %A Wei Ling Lau %A Nosratola D. Vaziri %T Phosphate binder, ferric citrate, attenuates anemia, renal dysfunction, oxidative stress, inflammation and fibrosis in 5/6 nephrectomized CKD rats %D 2018 %R 10.1124/jpet.118.249961 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.118.249961 %X Chronic kidney disease (CKD) causes anemia and impairs intestinal iron absorption. However, use of the phosphate binder, ferric citrate (FC), increases body iron stores and hemoglobin levels in CKD patients. By intensifying oxidative stress and inflammation iron overload can accelerate CKD progression. Present study explored the route of absorption and tissue distribution of iron with FC administration and its effect on renal function, histology and inflammatory, oxidative and fibrosis pathways in CKD rats. Male Sprague Dawley rats were randomized to sham-operated control (CTL) group and 5/6 nephrectomized (CKD) groups fed either regular or 4% FC-supplemented diets for 6 weeks. Animals were then sacrificed, and blood and target tissues were harvested and processed. The untreated CKD rats exhibited anemia, hypertension, upregulation of renal tissue inflammatory, oxidative and fibrotic pathways, impaired nuclear translocation and down-regulation of Nrf2's target gene products and depletion of colonic epithelial tight junction proteins. FC administration raised serum iron, improved anemia, attenuated hyperphosphatemia, partially improved renal function, reduced oxidative stress, inflammation and fibrosis, and restored colonic epithelial zonula occludence-1 protein abundance. Tissue iron staining detected presence of iron in epithelial cells and sub-epithelium of colon and in renal proximal tubules. In conclusion ferric citrate administration resulted in modest amelioration of renal function and histology and partial improvements of fibrosis, inflammation and oxidative stress, in the kidney tissues of CKD rats. %U https://jpet.aspetjournals.org/content/jpet/early/2018/08/09/jpet.118.249961.full.pdf