Neuroprotective effects of coenzyme Q10 at rostral ventrolateral medulla against fatality during experimental endotoxemia in the rat.
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.
Center for Neuroscience and Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan, Republic of China.
Yao-Chung
YC
Chuang
Julie Y H
JY
Chan
Alice Y W
AY
Chang
Marianna
M
Sikorska
Henryk
H
Borowy-Borowski
Chai-Wei
CW
Liou
Samuel H H
SH
Chan
D000818:Animals; D003067:Coenzymes; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000401:mortality* / Q000473:pathology*; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000473:pathology*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D003067:Coenzymes; D008070:Lipopolysaccharides; D013481:Superoxides; D014451:Ubiquinone; C024989:coenzyme Q10