Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

Figure 5 Milk fat globule epidermal growth factor 8 administration mitigates hepatic autophagy and ferroptosis in experimental severe acute pancreatitis. In mice, arginine-severe acute pancreatitis was induced by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine. At 2 h after the last injection of L-arginine, normal saline (vehicle) or 10, or 20 μg/kg milk fat globule epidermal growth factor 8 (MFG-E8) was administered through intraperitoneal injection. The animals were sacrificed at 69 h after MFG-E8 treatment (i.e., 72 h after the first injection of L-arginine). Blood and tissue samples were collected. A-D: Western blot analysis and quantitative of the expression of autophagy related protein 16 like protein 1, P62, LC3, prostaglandin-endoperoxide synthase 2 and glutathione peroxidase 4 in the liver; E: Malondialdehyde levels in the liver; F: Representative images of DHE staining in the pancreas; G: Glutathione levels in the liver; H: Ultrastructural changes of mitochondria in hepatocytes (electron microscopy). n = 3-6/group, error bars indicate the SEM; ^aP < 0.05 vs sham group; ^bP < 0.05 vs vehicle group. SAP: Severe acute pancreatitis; ATG16L1: Autophagy related protein 16 like protein 1; PTGS2: Prostaglandin-endoperoxide synthase 2; GPX4: Glutathione peroxidase 4; MDA: Malondialdehyde; GSH: Glutathione; MFG-E8: Milk fat globule epidermal growth factor 8.