Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice

• Published in: Scientific reports Vol. 7; no. 1; pp. 10621 - 10
• Main Authors: Ikeda, Yasumasa, Horinouchi, Yuya, Hamano, Hirofumi, Hirayama, Tasuku, Kishi, Seiji, Izawa-Ishizawa, Yuki, Imanishi, Masaki, Zamami, Yoshito, Takechi, Kenshi, Miyamoto, Licht, Ishizawa, Keisuke, Aihara, Ken-ichi, Nagasawa, Hideko, Tsuchiya, Koichiro, Tamaki, Toshiaki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.09.2017; Nature Publishing Group
• Subjects: 38/77; 64/60; 692/4022/1585/104; 692/4022/1585/2760; 82/51; 82/80; Acute Kidney Injury - diet therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Animal models; Animals; Biomarkers; Bovine serum albumin; Cytokines; Cytokines - metabolism; Dietary restrictions; Disease Models, Animal; Extracellular matrix; Gene expression; Humanities and Social Sciences; Immunohistochemistry; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation Mediators - metabolism; Iron; Iron - metabolism; Iron, Dietary; Kidney Function Tests; Kidneys; Macrophages; Male; Mice; multidisciplinary; NAD(P)H oxidase; NADPH Oxidases - metabolism; Nephritis, Interstitial - diet therapy; Nephritis, Interstitial - etiology; Nephritis, Interstitial - metabolism; Nephritis, Interstitial - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Overdose; Oxidative Stress; Proteins; Proteinuria; Proteinuria - complications; Proteinuria - metabolism; Pyrin protein; Renal function; Rodents; Science; Science (multidisciplinary); Serum Albumin, Bovine - administration & dosage; Serum Albumin, Bovine - adverse effects; Superoxide
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11089-0

Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22 phox expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.