Effect of Sulfasalazine on Ferroptosis during Intestinal Injury in Rats after Liver Transplantation

Abstract

Abstract Background and Objectives: Liver transplantation is an effective treatment for end-stage liver disease, but the perioperative period of liver transplantation will not only cause damage to the liver itself, but also cause damage to distant extrahepatic organs.Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia-reperfusion (I/R)-induced intestinal injury, we investigated the action of the lipid reactive oxygen species (L-ROS) inhibitor ferrostain-1（FER-1）on the ferroptosis signaling pathway and clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Methods:Sixty SPF-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12). The inferior vena cava blood was collected at 6 h and 24 h after the portal vein was opened, and the ileal tissue was obtained at the same time. The corresponding indexes were detected by different methods. Results: Compared with the Sham group, the Chiu's score and W/D ratio increased 6h and 24h after modeling in other groups, and the expression of GPX4 and xCT protein in intestinal tissue decreased. Compared with the SAS group, the levels of SOD, GSH and GPX4 in the intestinal tissue increased in the I/R+SAS+Fer-1 group, and the expression of GPX4 and xCT protein in the intestinal tissue increased. Conclusions:Ferroptosis is involved in the pathophysiological process of intestinal injury induced by cold hepatic ischemia-reperfusion in AOLT rats.In addition, SAS (500mg/kg) may inhibit the System Xc¯/GSH/GPX4 signal axis in intestinal injury induced by cold I/R in rat AOLT liver, or iron overload after reperfusion, causing a massive accumulation of L-ROS and activating cellular ferroptosis, Further aggravate the intestinal injury.