Repeated Restraint Stress Enhances Hepatic TFR2 Expression and Induces Hepatic Iron Accumulation in Rats

Abstract

Abnormal hepatic iron metabolism is detrimental to health. The objective of this study was to detect repeated restraint stress on liver iron metabolism in rats. Twenty-four male rats aged 7 weeks were randomly divided into 2 groups: control group (Con) and repeated restraint stress group (RS). Rats were subjected to 6 h of daily restraint stress for 14 consecutive days in the repeated restraint stress group. The results showed that repeated restraint stress exposure decreased growth performance including impaired final weight (P = 0.07), reducing average daily gain (P = 0.01), and average daily feed intake (P = 0.00) during the 14-day experimental period. Repeated restraint stress exposure did not affect hemoglobin content and plasma iron parameters except downregulated unsaturated iron-binding capacity (P = 0.04). Repeated restraint stress exposure inhibited liver development (P = 0.03) and induced liver iron accumulation (P = 0.05). In addition, repeated restraint stress downregulated the expression of transferrin (TF) and transferrin receptor 2 (TFR2) at the mRNA level (P < 0.01), but upregulated at the protein level (P = 0.03 for TF; P = 0.00 for TFR2). These results indicated that repeated restraint stress induces hepatic iron accumulation, which is closely related to higher expression of hepatic TFR2 protein in rats.