Intestinal ischemia is an abdominal emergency that accounts for approximately 2 % of gastrointestinal diseases [1]. Intestinal ischemia caused by strangulated intestinal obstruction and non-occlusive mesenteric ischemia is common in gastrointestinal surgery. Once ischemia becomes irreversible, even if strangulation is released, the intestine cannot be preserved [2], [3]. Vascular intestinal obstruction (Vio) is a type of strangulated intestinal obstruction. The mechanisms of Vio are complex, including tissue intestinal injury as well as oxidative stress after reperfusion of the blood, which ultimately leads to destruction of the intestinal mucosa, enhanced vascular permeability and release of pro-inflammatory factors [4].

Ferroptosis is a form of lipid peroxidation catalyzed by iron accumulation which in turn leads to cell death [5]. The process of ferroptosis is accompanied by inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and elevated levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4), which can act as a ferroptosis sensitive regulator [6], [7]. Previous studies has been demonstrated the role of ferroptosis in intestinal ischemia/reperfusion [5], [8]. However, the role of ferroptosis in intestinal ischemia remains unclear.

Ferric Chelate Reductase 1 (FRRS1), an enzyme that reduces Fe3+ to Fe2+, is located in the inner mitochondrial membrane and is involved in the electron transport chain and tricarboxylic acid (TCA) cycle [9]. It has been shown that patients with primary extremity soft tissue sarcoma with high FRRS1 expression have a favorable prognosis [10]. FRRS1 expression was higher in bladder cancer tissues than in paraneoplastic tissues [11]. FRRS1 exhibits different expression levels in different diseases [12], [13]. However, the biological function of FRRS1 in intestinal ischemia is unclear.

In the present study, we found that the levels of Fe and ACSL4 were elevated in intestinal ischemia tissues, whereas GPX4 level was decreased. RNA-seq showed that FRRS1 was significantly decreased in intestinal ischemia tissues, and this result was confirmed by real-time quantitative PCR (RT-qPCR), western blot, and immunohistochemical (IHC) staining. Our study aimed to explore the effect of FRRS1 on ferroptosis in intestinal ischemia injury, and its downstream mechanism.