Change in iron metabolism in rats after renal ischemia/reperfusion injury

Abstract

Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1) and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI). In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum creatinine and blood urea nitrogen were found to be time-dependently increased with different degrees of kidney injury. Regular variations in iron metabolism indexes in the blood and kidneys were observed in renal IRI. Renal iron content, serum iron and serum ferritin increased early after reperfusion and then declined. Hepcidin expression in the liver significantly increased early after reperfusion, and its serum concentration increased beginning at 8 h after reperfusion. The splenic iron content decreased significantly in the early stage after reperfusion and then increased time-dependently with increasing reperfusion time, and the hepatic iron content showed a decrease in the early stage after reperfusion. The early decrease of the splenic iron content and hepatic iron content might indicate their contribution to the increase in serum iron in renal IRI. In addition, the duodenal iron content showed time-dependently decreased since 12 h after reperfusion in the IRI groups compared to the control group. Along with the spleen, the duodenum might contribute to the decrease in serum iron in the later stage after reperfusion. The changes in iron metabolism indexes observed in our study demonstrate an iron metabolism disorder in renal IRI, and hepcidin might be involved in maintaining iron homeostasis in renal IRI. These findings might suggest a self-protection mechanism regulating iron homeostasis in IRI and provide a new perspective on iron metabolism in attenuating renal IRI.

Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury

“…Renal ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury (AKI) in patients suffering from sepsis, renal artery stenosis, renal transplantation and shock, and can also lead to high morbidity and mortality [1,2]. Moreover, renal I/R injury is closely related to acute tubular-epithelial injury, vascular dysfunction, inflammation and hemodynamic alterations [3,4].…”

Elevated serum iron level is a predictor of prognosis in ICU patients with acute kidney injury

“…A study in a rat model of ischaemia/reperfusion injury (IRI) reported no significant changes in total iron, non-haem or ferritin iron levels, but a significant increase in catalytic iron level after reperfusion [ 17 ]. IRI models may possess possible self-protection mechanisms for regulating iron homeostasis [ 18 ].…”

Elevated serum iron level is a predictor of prognosis in ICU patients with acute kidney injury

“…A study in a rat model of ischemia/reperfusion injury (IRI) showed that no significant changes in total iron, non-heme or ferritin iron levels were observed, but catalytic iron level significantly increased after reperfusion [10]. In IRI, there are possible self-protection mechanisms for regulating iron homeostasis [11]. In a rat of the cisplatin-induced nephrotoxicity model, research supported the key role of iron in mediating tissue damage through hydroxyl radicals (or similar oxidants) [12].…”