title: Mitochondrial anti-oxidant protects IEX-1 deficient mice from organ damage during endotoxemia.
abstract: Sepsis, a leading cause of mortality in intensive care units worldwide, is often a result of overactive and systemic inflammation following serious infections. We found that mice lacking immediate early responsive gene X-1 (IEX-1) were prone to lipopolysaccharide (LPS) -induced endotoxemia. A nonlethal dose of LPS provoked numerous aberrations in IEX-1 knockout (KO) mice including pancytopenia, increased serum aspartate aminotransferase (AST), and lung neutrophilia, concurrent with liver and kidney damage, followed by death. Given these results, in conjunction with a proven role for IEX-1 in the regulation of reactive oxygen species (ROS) homeostasis during stress, we pre-treated IEX-1 KO mice with Mitoquinone (MitoQ), a mitochondrion-based antioxidant prior to LPS injection. The treatment significantly reduced ROS formation in circulatory cells and protected against pancytopenia and multiple organ failure, drastically increasing the survival rate of IEX-1 KO mice challenged by this low dose of LPS. This study confirms significant contribution of mitochondrial ROS to the etiology of sepsis.
authors.forename: Haley
authors.initials: H
authors.lastname: Ramsey
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001772:Blood Cell Count; D003627:Data Interpretation, Statistical; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D004731:Endotoxins / Q000633:toxicity*; D017874:Immediate-Early Proteins / Q000172:deficiency* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D004731:Endotoxins; C518820:IEX-1 protein, mouse; D017874:Immediate-Early Proteins; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C429014:mitoquinone; C044101:endotoxin, Escherichia coli