coenzyme-q10 and Shock--Septic

We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.. We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models.. We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes.. In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population.. Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013.

Topics: Cholesterol; Cytochromes c; Double-Blind Method; Female; Humans; Interleukins; Male; Micronutrients; Middle Aged; Pilot Projects; Sepsis; Shock, Septic; Ubiquinone; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A

Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.. We conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient.. We analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r2 = 0.2; P = 0.008), TNF-α (r2 = 0.28; P = 0.004), IL-8 (r2 = 0.21; P = 0.015), IL-10 (r2 = 0.18; P = 0.025), E-selectin (r2 = 0.17; P = -0.03), IL-1ra (r2 = 0.21; P = 0.014), IL-6 (r2 = 0.17; P = 0.029) and IL-2 (r2 = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r2 = 0.24; P = 0.01) (Figure 3) and IL-10 (r2 = 0.24; P = 0.02).. CoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels.

Topics: Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Prospective Studies; Shock, Septic; Ubiquinone; Vascular Cell Adhesion Molecule-1; Vitamins

The present study was designed to evaluate the possible protective effect of quercetin, coenzyme Q10 (CoQ10), or L-canavanine treatments against endotoxin-induced shock in rat brain. Shock was induced by i.p. injection of 10 mg x kg(-1)of lipopolysaccharide (LPS) and was biochemically manifested 2 h after injection as an increase in brain malondialdehyde (MDA), total nitrite/nitrate (NO(x)), glutathione peroxidase (GSHPx), and blood lactate level/activity. On the other hand, endotoxemia resulted in reduced brain glutathione (GSH) and phospholipids' content as well as the serum sulfhydryl groups' (SH-group) value. Pretreatment with quercetin (200 mg x kg(-1)per os) 2 h before LPS injection diminished the shock-induced increases in brain MDA, and NO(x)levels while elevating the reduced brain phospholipids' and serum SH groups' content. CoQ10 administered at a dose of 200 mg x kg(-1)per os for 7 days prior to shock induction, reduced the elevated levels of brain MDA, NO(x), and GSHPx level/activity due to redundancy. The same treatment caused a 3-fold increase in the reduced brain GSH level and normalized the depressed phospholipids' content. Treatment of animals with L-canavanine (50 mg x kg(-1)i.p.) simultaneously with LPS injection, reduced the elevated level of blood lactate. Brain superoxide dismutase (SOD) level was neither affected by endotoxin nor by different treatments. In conclusion, this study indicates that SOD may not reflect the level of peroxidation and points to the value of quercetin, CoQ10, and L-canavanine in ameliorating the oxidative status of brain during the early phase of endotoxic shock.

Topics: Animals; Brain; Canavanine; Coenzymes; Endotoxins; Glutathione; Glutathione Peroxidase; Lactic Acid; Lipid Peroxidation; Male; Malondialdehyde; Nitric Oxide; Phospholipids; Protective Agents; Quercetin; Rats; Rats, Wistar; Shock, Septic; Sulfhydryl Compounds; Superoxide Dismutase; Ubiquinone

The effect of coenzyme Q10 (CoQ10) on hepatocyte injury during endotoxin (ET) shock in rats was studied with special reference to the role of polymorphonuclear neutrophils (PMN). ET shock was induced by intravenous administration of 5 mg/kg ET, and CoQ10 was given at 20 mg/kg once or 3 times orally or intravenously. We examined plasma glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and glutamate dehydrogenase (GLDH) levels, superoxide production by PMN, the phagocytic activity of PMN, the cytotoxicity of PMN to liver cells, and histological changes in the liver. The CoQ10-treated rats showed lower levels of GOT, GPT, and GLDH than rats treated with ET only. When compared to the group given ET only superoxide production by PMN induced by 2-methyl-6-phenyl-3,7-dihydroimidazol [1,2-alpha]pyrazin-3-one (MCLA) was significantly inhibited in the group given CoQ10 intravenously and 3 times orally, but there was no significant difference in the group given CoQ10 once orally. However, the level of superoxide production by PMN stimulated by phorbol myristate acetate (PMA) was lower in all CoQ10-treated rats than in those given ET only. There was no difference in either peripheral PMN counts or PMN phagocytes between the CoQ10-treated group and the group given ET only. Histologically, the hepatocyte injury in all groups that received CoQ10 was milder than that in the ET-only group. No hepatocyte cytotoxicity by PMN was observed in any group that received CoQ10. These results suggest that both intravenous and oral administration of CoQ10 can modulate the endotoxin-activated PMN, and is useful for preventing hepatocyte injury during ET shock.

Topics: Animals; Coenzymes; Disease Models, Animal; Liver Diseases; Male; Neutrophils; Phagocytosis; Rats; Rats, Wistar; Shock, Septic; Superoxides; Ubiquinone

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.

Topics: Animals; Arachidonic Acid; Blood Pressure; Cardiac Output; Catecholamines; Coenzymes; Dogs; Escherichia coli Infections; Interleukin-6; Lipid Peroxides; Shock, Septic; Tumor Necrosis Factor-alpha; Ubiquinone

The present study was designed to determine the superoxide production of polymorphonuclear leukocytes (PMN) in endotoxin shock and the antioxidative effect of coenzyme Q10. PMN were collected from rats before and after the intravenous administration of endotoxin. PMN were also collected from healthy humans. Superoxide production of PMN was measured by the cytochrome C method. Lipid peroxide in the liver was examined by the TBA method. Twelve hours after the intravenous administration of 5 mg/kg endotoxin, superoxide production of PMN was 13 times higher than that in the control rats, and the amount of lipid peroxide in the liver was increased. In coenzyme Q10 treated endotoxin shock rats, superoxide production was significantly decreased, and lipid peroxide production in the liver was also inhibited. These findings suggest that endotoxin has a priming effect on the superoxide production of PMN and induces lipid peroxidation. Furthermore coenzyme Q10 has an anti-endotoxin shock effect by inhibiting the superoxide production of PMN and lipid peroxidation in the liver.

Topics: Animals; Coenzymes; Free Radicals; Lipid Peroxides; Liver; Male; Mice; Neutrophils; Rats; Rats, Inbred Strains; Shock, Septic; Superoxides; Ubiquinone

Topics: Animals; Coenzymes; Free Radicals; Lipid Peroxides; Liver Transplantation; Rats; Reperfusion Injury; Shock, Septic; Superoxide Dismutase; Ubiquinone

Intraperitoneal injection of endotoxin (lipopolysaccharide, [LPS]) to mice at a dose of 15 mg/kg of body weight resulted in a survival rate of 31% 48 hours after administration. Simultaneous intramuscular administration of (10 mg/kg) coenzyme Q10 (CoQ10) increased the survival rates of LPS-administered mice to 69.7%. When LPS administration was increased to 30 mg/kg, no survivors were observed in the placebo group. Simultaneous intravenous injection of CoQ10 (10 mg/kg) or alpha-tocopherol (20 mg/kg) restored the survival rate to 52.9% or 42.9%, respectively. The adenosine triphosphate (ATP) level in the liver, which is the best index of the energy state, decreased gradually to 70% of the control ATP level 24 hours after LPS (15 mg/kg) administration. The lipid peroxide level in the liver increased fivefold 16 hours after LPS administration and then decreased to the control level in 8 hours. Simultaneous treatment of mice with antioxidants, such as CoQ10 or alpha-tocopherol, completely suppressed the lipid peroxide level in the liver and preserved the hepatic ATP level in the normal range. These results indicate that LPS induced hepatic damage in mice because of lipid peroxidation and that antioxidants suppressed lipid peroxidation, preserved energy metabolism in the liver, and enhanced survival of endotoxin-administered mice.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Coenzymes; Lipid Peroxides; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Mice; Models, Biological; Shock, Septic; Ubiquinone; Vitamin E

We studied the effects of coenzyme Q10 pretreatment on both pulmonary function and chemical mediators during endotoxin shock in dogs. Coenzyme Q10 pretreatment inhibited disturbances in peak airway pressure, total compliance of lung plus chest wall, lung clearance index, plasma histamine, base excess, and lactate; however, it had little effect on the circulation. The mechanism of coenzyme Q10's significant effects on pulmonary function during endotoxin shock is presently unknown.

Topics: Animals; Blood Gas Analysis; Cardiac Output; Coenzymes; Dogs; Female; Hemodynamics; Histamine; Hydrogen-Ion Concentration; Lung Compliance; Male; Pulmonary Gas Exchange; Respiratory Function Tests; Shock, Septic; Ubiquinone

Topics: Animals; Catecholamines; Coenzymes; Dogs; Hemodynamics; Shock, Septic; Ubiquinone; Vascular Resistance; Vasopressins

Topics: Animals; Chlorpromazine; Coenzymes; Fatty Acids, Nonesterified; Female; Lung; Microsomes; Phospholipases A; Rats; Rats, Inbred Strains; Shock, Septic; Ubiquinone