a-Lipoic acid protects mitochondrial enzymes and attenuates
lipopolysaccharide-induced hypothermia in mice.
Authors Hiller S, DeKroon R, Xu L, Robinette J, Winnik W, Alzate O, Simington S, Maeda
N, Yi X
Submitted By Xianwen Yi on 3/4/2015
Status Published
Journal Free radical biology & medicine
Year 2014
Date Published 6/1/2014
Volume : Pages 71 : 362 - 367
PubMed Reference 24675228
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 a-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.

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina
Xianwen YiUniversity of North Carolina at Chapel Hill