Figure 13.

Proposed mechanisms underlying protective effects of exosome-melatonin treatment against liver ischemia-reperfusion injury based on findings of this study. A: Suppression of inflammatory responses (i.e., upregulated expressions of pro-inflammatory biomarkers) in macrophage in vitro by exosomes after lipopolysaccharide (LPS) pre-treatment. B: In vitro alleviation of oxidative stress and apoptosis in hepatocytes after exosome/melatonin treatment before hypoxic stimulation. C: In vivo impacts of exosome/melatonin treatment on inflammation, oxidative stress, DNA damage, mitochondrial damage, apoptosis, and immune reactions that contribute to impaired hepatocyte and histological integrity. LPS: lipopolysaccharide, MIF: migration inhibitory factor, MMP-9: matrix metalloproteinase 9, TNF-α: tumor necrosis factor alpha, IL-1β: interleukin-1 beta, COX-2: cyclooxygenase-2, NOX-1: NADPH oxidase 1, NOX-2: NADPH oxidase 2, c-Casp 3: cleaved caspase 3, c-PARP: cleaved poly ADP ribose polymerase, IL: interleukin, PBMNC: peripheral blood mononuclear cell, NF-κB: nuclear factor kappaB, ICAM-1: intercellular adhesion molecule 1, RANTES: regulated on activation, normal T cell expressed and secreted , HO-1: heme oxygenase-1, NQO: quinone oxidoreductase 1, cyt-Cyto C: cytosolic cytochrome C, mit-Cyto C: mitochondrial cytochrome C, AST: aspartate aminotransferase.