Effects of coenzyme Q10 on the mediator cascade of sepsis.
Coenzyme Q10 (CoQ) has been promoted as an effective agent for reducing the deleterious effects of septic shock by acting as an oxygen free radical scavenger and thus stabilizing mitochondrial membranes and by inhibiting the arachidonic acid metabolic pathway and the formation of various prostaglandins. This study was undertaken to evaluate the effect of CoQ in a live Escherichia coli model of canine septic shock. Group I (E. coli, n = 5) animals received an LD100 dose of 10(9) live E. coli/kg and were given no further treatment. Group II (CoQ, n = 5) animals received a 20-mg/kg bolus of CoQ without further treatment. Group III (CoQ + E. coli, n = 5) animals received a 20-mg/kg bolus of CoQ 10 min prior to a bacterial infusion as in group 1. Mean arterial pressure stabilized at 70% of baseline levels (P < .002), while cardiac output remained near 50% of baseline levels (P < .053) in group III compared to group I dogs. The arachidonic acid metabolites, prostaglandin E2, Thromboxane B2, and leukotriene B4 were significantly elevated in groups I and III (vs. group II) (P < 0.05). The catecholamines, tumor necrosis factor (TNF) and interleukin 6 (IL-6) were significantly elevated in groups I and III (vs. group II) (P < 0.05). Fluorescent products (lipid peroxidation activity) were elevated in group I (vs. groups II and III) at 120 and 180 min (P < 0.05). We conclude that CoQ supports cardiovascular hemodynamics and prevents free radical mediated lipid peroxidation during live E. coli septic shock, and its effect is not due to altered levels of humoral or cytokine mediators.
Lelli
J L
JL
Section of Pediatric Surgery, C.S. Mott Children's Hospital, Ann Arbor, Michigan.
Drongowski
R A
RA
Gastman
B
B
Remick
D G
DG
Coran
A G
AG
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003067:Coenzymes; D004285:Dogs; D004927:Escherichia coli Infections / Q000378:metabolism / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008054:Lipid Peroxides / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D002395:Catecholamines; D003067:Coenzymes; D015850:Interleukin-6; D008054:Lipid Peroxides; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; D016718:Arachidonic Acid; C024989:coenzyme Q10