Lipoxin A4 Preconditioning Attenuates Intestinal Ischemia Reperfusion Injury through Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor Independent Manner

Figure 7

Proposed signaling mechanisms mediated by Lipoxin A4 in preventing intestinal epithelium cells from intestine ischemia reperfusion (IIR) injury. Lipoxin A4 promotes Keap1 dissociation from Nrf2 and leads to Nrf2 translocation from cytoplasm to nucleus, resulting in enhancing downstream HO-1 gene expression without binding to the Lipoxin A4 receptor (ALXR). Antioxidant enzyme HO-1 could possibly reduce cytochrome C release from mitochondria and decrease lipid peroxidative product 15-F2t-Isoprostane and elevate cell antioxidant ability evidenced by increase of superoxide dismutase (SOD) and finally decrease cells apoptosis. In addition, Lipoxin A4 binding to ALXR could also reduce damage of diamine oxidase (DAO) products, D-lactic acid (DLA), and intestinal-type fatty acid-binding protein (FABP2) release with other mechanisms.