title: α-Lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice.
abstract: Hypothermia is a key symptom of sepsis, but the mechanism(s) leading to hypothermia during sepsis is largely unknown and thus no effective therapy is available for hypothermia. Therefore, it is important to investigate the mechanism and develop effective therapeutic methods. Lipopolysaccharide (LPS)-induced hypothermia accompanied by excess nitric oxide (NO) production leads to a reduction in energy production in wild-type mice. However, mice lacking inducible nitric oxide synthase did not suffer from LPS-induced hypothermia, suggesting that hypothermia is associated with excess NO production during sepsis. This observation is supported by the treatment of wild-type mice with α-lipoic acid (LA) in that it effectively attenuates LPS-induced hypothermia with decreased NO production. We also found that LA partially restored ATP production, and activities of the mitochondrial enzymes involved in energy metabolism, which were inhibited during sepsis. These data suggest that hypothermia is related to mitochondrial dysfunction, which is probably compromised by excess NO production and that LA administration attenuates hypothermia mainly by protecting mitochondrial enzymes from NO damage.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hiller
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: DeKroon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Longquan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Program of Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinette
authors.affiliation: Proteomic Research Core Unit, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, Durham, NC 27711, USA.
authors.forename: Witold
authors.initials: W
authors.lastname: Winnik
authors.affiliation: Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Alzate
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Simington
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA. Electronic address: xyi2000@med.unc.edu.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Yi
mesh_terms: D000255:Adenosine Triphosphate / Q000819:agonists / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D007036:Hypothermia, Induced; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D007655:Ketoglutarate Dehydrogenase Complex; D014450:Electron Transport Complex III
keywords: Antioxidant; Body energy; Free radicals; Lipoic acid; Mitochondria