Coenzyme Q10 (
CoQ10,
ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an
antioxidant. We evaluated the neuroprotective efficacy of
CoQ10 against fatality in an experimental model of
endotoxemia that mimics
systemic inflammatory response syndrome using a novel water-soluble formulation of this
quinone derivative. Experiments were conducted in adult male Sprague-Dawley rats that were maintained under
propofol anesthesia.
Intravenous administration of Escherichia coli
lipopolysaccharide (LPS; 30 mg/kg) induced progressive
hypotension, with death ensuing within 4 h. The sequence of cardiovascular events during this LPS-induced
endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; "pro-life" phase) and a secondary decrease (Phase III; "pro-death" phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure signals. Pretreatment by microinjection bilaterally of
CoQ10 (1 or 2 microg) into the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-
induced hypotension.
CoQ10 pretreatment also significantly prolonged the duration of and augmented the total power density of the vasomotor components of systemic arterial pressure signals in Phase II
endotoxemia. The increase in
superoxide anion production induced by LPS at the RVLM during Phases II and III
endotoxemia was also significantly blunted. We conclude that
CoQ10 provides neuroprotection against fatality during experimental
endotoxemia by reducing
superoxide anion production at the RVLM, whose neuronal activity is intimately related to the "life-and-death" process.