Ferroptosis in intestinal ischemia-reperfusion injury: a systematic review and meta-analysis

PURPOSE: This meta-analysis evaluated changes in ferroptosis-related factors during intestinal ischemia-reperfusion injury by integrating data from animal experiments. METHODS: Five databases were searched and 11 studies were selected from an initial pool of 105 publications. Primary indicators included Chiu's score, Fe²⁺, and Glutathione Peroxidase 4 (GPX4), while secondary metrics included malondialdehyde (MDA), glutathione (GSH), reduced glutathione/oxidized glutathione (GSH/GSSG), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), and Superoxide Dismutase (SOD). Sensitivity analyses were performed to assess heterogeneity and ensure the stability of the results. Funnel plots were employed to address publication bias. Statistical analyses were conducted using Review Manager 5.3. RESULTS: The meta-analysis of the eleven selected studies indicated that intestinal IRI significantly increased Chiu's score (standard mean difference: 4.97, P < 0.00001) and oxidative stress markers such as MDA (5.41, P < 0.00001) while decreasing SOD levels (5.64, P = 0.01). Ferroptosis was significantly increased during intestinal IRI, as shown by the elevation of Fe²⁺ (4.31, P < 0.00001) and reductions in GPX4 (-4.43, P < 0.00001), GSH (-2.45, P < 0.00001), GSH/GSSG (-3.69, P < 0.00001), SLC7A11 (-3.61, P = 0.02), and FTH1 (-3.10, P < 0.0001). CONCLUSION: Intestinal IRI leads to increased Chiu's score, MDA, and Fe²⁺ levels, alongside decreased levels of GPX4, GSH, GSH/GSSG, FTH1, and SLC7A11, all of which are associated with the promotion of ferroptosis. The ischemia model employing 45 minutes of ischemia appears to yield superior outcomes regarding the evaluated markers.