Elevated luminal inorganic phosphate suppresses intestinal Zn absorption in 5/6 nephrectomized rats

Am J Physiol Renal Physiol. 2024 Jan 18. doi: 10.1152/ajprenal.00310.2023. Online ahead of print.ABSTRACTZinc (Zn) is an essential trace element in various biological processes. Chronic kidney disease (CKD) often leads to hypozincemia, resulting in further progression of CKD. In CKD, intestinal Zn absorption, the main regulator of systemic Zn metabolism, is often impaired; however, the mechanism underlying Zn malabsorption remains unclear. Here, we evaluated intestinal Zn absorption capacity in a rat model of CKD induced by 5/6 nephrectomy (5/6 Nx). Rats were given Zn and the incremental area under the plasma Zn concentration-time curve (iAUC) was measured, as well as expression of ZIP4, an intestinal Zn transporter. We found that 5/6 Nx rats showed lower iAUC than sham-operated rats, but expression of ZIP4 protein was upregulated. We therefore focused on other Zn absorption regulators to explore the mechanism by which Zn absorption was substantially decreased. Because some phosphate compounds inhibit Zn absorption by co-precipitation and hyperphosphatemia is a common symptom in advanced CKD, we measured inorganic phosphate (Pi) levels. Pi was elevated not only in serum but also in the intestinal lumen of 5/6 Nx rats. Furthermore, intestinal intraluminal Pi administration decreased the iAUC in a dose-dependent manner in normal rats. In vitro, increased Pi concentration decreased Zn solubility under physiological conditions. Furthermore, dietary Pi restriction ameliorated hypo...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Source Type: research