Coenzyme Q10 concentration in plasma and blood cells of juvenile patients hospitalized for anorexia nervosa

The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 °C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients.     

Coenzyme Q10 in maternal plasma and milk throughout early lactation

In contrast to other lipophilic antioxidants Coenzyme Q10 originates from food intake as well as from endogenous synthesis. The CoQ10 concentration and lipid content of maternal milk and maternal plasma was investigated during early lactation. Breast milk was obtained from 23 women: A: colostrums (24-48 hours postpartum), B: transitional milk (day 7 pp), C: mature milk (day 14 pp). At the same time capillary blood specimens were collected. Milk and plasma were stored at -84 degrees C until CoQ10 was analysed after hexane extraction by HPLC. The lipid content was determined by PAP-analysis of cholesterol. The plasma content of CoQ10 was the highest soon after delivery (A: 1.29, B:1.20, C:1.07 pmol/microl; Wilcoxon p < 0.05 A vs. C and B vs. C). This tendency was still evident after lipid-adjustment (A:209, B:180, C:175 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.01 A vs. B and C). The level of CoQ10 in milk showed a gradual decline during early lactation (A:0.80, B:0.57, C:0.44 pmol/microl; Wilcoxon p < 0.02 A vs. B and C). After lipid-adjustment this tendency became even more evident (A: 137, B:86, C:67 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.002 A vs. B and C, p < 0.05 B vs. C). The content of CoQ10 in plasma and milk showed a correlation with early milk (Spearman p < 0.005) but not with mature milk. Although lipid content is low the colostrums is a rich source for the lipophilic antioxidant CoQ10.     

Coenzyme Q10 treatment in serious heart failure.

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.     

Granulocytopoiesis in children with acute lymphoblastic leukaemia.

Numbers, proliferative potential, and differentiative capacity of bone marrow granulocyte-macrophage precursor cells were studied in 130 children with acute lymphoblastic leukaemia (ALL), including 77 children in an acute phase of the disease and 53 in remission. Bone marrow samples from 65 children without haematopoietic abnormalities were used as controls. The numbers of clonogenic precursors were found to be below normal in all phases of ALL, particularly during the acute period when the bone marrow was heavily infiltrated with leukaemic cells. It is shown that the decreases in the numbers and proliferative potential of the precursor cells during the acute phases was associated with the effects of leukaemic blast cells, but that in remission the observed reduction in the precursor cell pool was due to the cytostatic effect of therapy. The differentiative capacity of clonogenic granulocyte and macrophage precursors was not altered in children with ALL.     

Remission induction with cytosine arabinoside and L-Asparaginase in acute lymphoblastic leukaemia

Nine patients with acute lymphoblastic leukaemia in relapse were treated with a course of cytosine arabinoside followed immediately by a course of L-asparaginase. Eight patients achieved complete remission of their disease. This combination of drugs is sufficiently effective to suggest that further trial is needed. It is possible that the combination has a synergistic effect.     

快速提取类球红细菌中辅酶Q10的方法研究

目的：建立一种从类球红细菌中快速分离纯化辅酶Q10的方法。方法：对影响超声提取辅酶Q10的各因素,包括提取试剂、超声频率、循环次数及工作时间的最佳条件进行正交试验,比较超声破碎法与碱醇皂化法提取辅酶Q10的差异。结果：在超声提取中,提取试剂和循环次数对辅酶Q10提取效果具有显著性影响;在超声频率0.5s、丙酮提取3min、循环3次的条件下提取的辅酶Q10的含量比碱醇皂化法提高了近6倍。结论：超声破碎法是一种简单、迅速、高效的提取辅酶Q10方法。     

Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia.

A one-hour D-xylose absorption test was performed on 18 children with acute lymphoblastic leukaemia. Xylose absorption was normal in children who had not received methotrexate, but there was a significant degree of malabsorption in those who had taken methotrexate within the previous seven days. There was a progressive and significant increase in malabsorption related to the cumulative dose of methotrexate. These findings provide further evidence that regular methotrexate treatment every seven days is more toxic than if it is more widely spaced. The spacing of treatment is currently under investigation.     

Coenzyme Q10 is increased in placenta and cord blood during preeclampsia

Preeclampsia is a common (approximately 7% of all pregnancies) disorder of pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the levels of coenzyme Q(10) (CoQ(10)) in placental tissue compared to maternal and umbilical cord levels both during normal pregnancy and in those complicated with preeclampsia. Pregnant women (n = 30) and women with preeclampsia (n = 30) were included. Maternal, newborn cord blood levels and placental content of coenzyme Q(10) were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q(10) levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ(10) content in placenta from women with preeclampsia (mean 0.28 SEM 0.11 nmol/mg protein) was significantly higher compared to normal pregnancy (mean 0.09 SEM 0.01 nmol/mg protein; p = 0.05). Levels of CoQ(10) in cord blood from normal pregnant women (mean 0.30 SEM 0.05 micromol/l) were significantly lower than in preeclamptic women (mean 4.03 SEM 2.38 micromol/l). In conclusion, these data indicate a possible involvement of CoQ(10) in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated.     

Coenzyme Q10 in phenylketonuria and mevalonic aciduria

Mevalonic aciduria (MVA) and phenylketonuria (PKU) are inborn errors of metabolism caused by deficiencies in the enzymes mevalonate kinase and phenylalanine 4-hydroxylase, respectively. Despite numerous studies the factors responsible for the pathogenicity of these disorders remain to be fully characterised. In common with MVA, a deficit in coenzyme Q₁₀ (CoQ₁₀) concentration has been implicated in the pathophysiology of PKU. In MVA the decrease in CoQ₁₀ concentration may be attributed to a deficiency in mevalonate kinase, an enzyme common to both CoQ₁₀ and cholesterol synthesis. However, although dietary sources of cholesterol cannot be excluded, the low/normal cholesterol levels in MVA patients suggests that some other factor may also be contributing to the decrease in CoQ₁₀.The main factor associated with the low CoQ₁₀ level of PKU patients is purported to be the elevated phenylalanine level. Phenylalanine has been shown to inhibit the activities of both 3-hydroxy-3-methylglutaryl-CoA reductase and mevalonate-5-pyrophosphate decarboxylase, enzymes common to both cholesterol and CoQ₁₀ biosynthesis.Although evidence of a lowered plasma/serum CoQ₁₀ level has been reported in MVA and PKU, few studies have assessed the intracellular CoQ₁₀ concentration of patients. Plasma/serum CoQ₁₀ is influenced by dietary intake as well as its lipoprotein content and therefore may be limited as a means of assessing intracellular CoQ₁₀ concentration. Whether the pathogenesis of MVA and PKU are related to a loss of CoQ₁₀ has yet to be established and further studies are required to assess the intracellular CoQ₁₀ concentration of patients before this relationship can be confirmed or refuted.     

辅酶Q10的生理作用及临床应用

辅酶Q10是线粒体电子传递链中的一种重要辅酶,参与细胞氧化磷酸化及ATP生成过程。辅酶Q10是细胞代谢呼吸激活剂和免疫增强剂,具有抗氧化和自由基清除功能。辅酶Q10药物的临床应用主要在心血管疾病、高血压、神经系统疾病和免疫系统疾病方面。     

Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age‐related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri‐phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age‐related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte‐specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte‐specific Pdss2‐deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age‐associated oocyte deficits causing infertility.     

皂化法分离测定三孢布拉氏霉菌体中辅酶Q10的研究

目的:为研究醇碱皂化法分离三孢布拉氏霉菌体中辅酶Q10的最佳工艺。方法:采用正交实验,对醇碱皂化法分离测定三孢布拉氏霉菌体中辅酶Q10的各工艺条件进行了研究。结果:皂化时间、醇碱浓度及焦性没食子酸添加量对皂化效果影响显著,而温度(50~90℃)对其影响较小。醇碱皂化法提取三孢布拉氏霉中辅酶Q10的最佳工艺条件为:KOH加入量为湿菌体的1/2(w/w),醇碱浓度为10%,焦性没食子酸量添加量为湿菌体的10%(w/w),在70℃下皂化60min。此提取工艺平均回收率达81.8%,RSD为2.6%。     

Coenzyme Q10 supplementation and recovery from ischemia in senescent rat myocardium

Many studies have suggested that parenteral administration of coenzyme Q10 (Q10) protects the myocardium of young experimental animals from post-ischemic reperfusion injury. Although parenteral administration, in contrast to per os supplementation, seems to elevate coenzyme Q concentrations in heart tissue, it is not suitable for prophylactic use. In addition, the incidence of ischemic events is greatest in older age. We studied the effect of Q10 supplementation on myocardial postischemic recovery in 18-month-old Wistar rats. The treated group (n=9) received 10 mg/kg/day of Q10 for 8 weeks in their chow while the normal chow of the control group (n=9) contained less than 0.5 mg/kg/day of Q10. The treatment clearly elevated plasma Q10 concentration (286 +/- 25 micromol/l and 48 +/- 30 micromol/l, treated and controls, respectively, p<0.0001) but neither Q9 nor Q10 concentrations in heart tissue were affected by the supplementation. The isolated perfused hearts were subjected to 20 minutes of ischemia and 30 minutes of reperfusion. The preischemic values of developed pressure (DP) but not contractility (+DP/delta t) and relaxation (-DP/delta t) were improved by Q10 supplementation (p=0.034, p=0.057 and p=0.13, respectively) while in postischemic recovery no differences were observed between the groups (p>0.05 at all time points). Also, in myocardial flow, myocardial oxygen consumption (MVO2) and myocardial aerobic efficiency (DP/MVO2) the groups did not differ at any time points. Although dietary Q10 supplementation clearly elevated plasma Q10 concentrations in senescent rats, the coenzyme Q contents in heart tissue and myocardial recovery from ischemia were not affected. However, it is possible that the site of action for the reported beneficial effects of Q10 is in the coronary endothelium rather than myocardium itself.     

Myeloid stem cell kinetics in children hypertransfused during remission induction of acute lymphoblastic leukemia

Experimental studies in animals and recent preliminary clinical evidence raised the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis recovery following irradiation or chemotherapy. This prompted us to design a study to determine the effect of hypertransfusion on the blood and marrow CFU-c of leukemic children during remission induction. Nineteen children with acute lymphoblastic leukemia have been randomized in pairs to normotransfused (Hb: 12-14 g/dl) and hypertransfused (Hb: 16-18 g/dl) groups. Anti-leukemic chemotherapy (vincristine and adriamycin weekly during 4 weeks and prednisone daily) was identical in all children. As expected, suppression of erythropoiesis was observed in the hypertransfused group. During the first three courses of chemotherapy, the number of marrow CFU-c remained very low in both groups. One week after the third course of chemotherapy the number of bone marrow CFU-c began to increase in both groups. One week after course four the CFU-c value was significantly larger in the hypertransfused group. We also observed that circulating CFU-c were almost absent before induction chemotherapy, whereas their number increased after course three and was higher in the hypertransfused group and remained higher after course four. These results show the kinetics of bone marrow recovery after chemotherapy and suggest that hypertransfusion increases the rate of recovery of granulopoiesis.     

Acute pancreatitis during L-asparaginase treatment in children with acute lymphoblastic leukemia

L-asparaginase (L-ASPA) has been put to a wide application in many therapeutic protocols, above all in the treatment of acute lymphoblastic leukemia (ALL). We presented three cases of acute pancreatitis in children with ALL induced by administration of L-ASPA preparations. Our observations revealed that ultrasound investigations are very useful in diagnosis and monitoring changes in the pancreas. The use of L-ASPA derivatives allows to decrease the toxic and allergic sequele resulting from the administration of the drug.     

Coenzyme Q10: absorption, antioxidative properties, determinants, and plasma levels

The purpose of this article is to summarise our studies, in which the main determinants and absorption of plasma coenzyme Q10 (Q10, ubiquinone) have been assessed, and the effects of moderate dose oral Q10 supplementation on plasma antioxidative capacity, lipoprotein oxidation resistance and on plasma lipid peroxidation investigated. All the supplementation trials carried out have been blinded and placebo-controlled clinical studies. Of the determinants of Q10, serum cholesterol, serum triglycerides, male gender, alcohol consumption and age were found to be associated positively with plasma Q10 concentration. A single dose of 30 mg of Q10, which is the maximum daily dose recommended by Q10 producers, had only a marginal elevating effect on plasma Q10 levels in non-Q10-deficient subjects. Following supplementation, a dose-dependent increase in plasma Q10 levels was observed up to a daily dose of 200 mg, which resulted in a 6.1-fold increase in plasma Q10 levels. However, simultaneous supplementation with vitamin E resulted in lower plasma Q10 levels. Of the lipid peroxidation measurements, Q10 supplementation did not increase LDL TRAP, plasma TRAP, VLDL+LDL oxidation resistance nor did it decrease LDL oxidation susceptibility ex vivo. Q10 with minor vitamin E dose neither decreased exercise-induced lipid peroxidation ex vivo nor muscular damage. Q10 supplementation might, however, decrease plasma lipid peroxidation in vivo , as assessed by the increased proportion of plasma ubiquinol (reduced form, Q10H 2 ) of total Q10. High dose vitamin E supplementation decreased this proportion, which suggests in vivo regeneration of tocopheryl radicals by ubiquinol.     

Coenzyme Q10, carotenoid,tocopherol, and retinol levels in cord plasma from multiethnic subjects in Hawaii

Abstract

Coenzyme Q10 (Q10), carotenoids, tocopherols, and retinol are the major circulating lipid-phase micronutrients (LPM) known to help mitigate oxidative damage and prevent chronic diseases. However, the functions of these compounds in newborns are little understood. This is due, in part, to the paucity of studies reporting their concentrations in this population.

We measured Q10, carotenoids, tocopherols, and retinol in cord plasma from 100 multiethnic subjects living in Hawaii using HPLC with diode array and electrochemical detection. Appropriate internal standards were used including, for the first time, custom designed oxidized (UN10) and reduced (UL10) Q10 analogues. These compounds reflected the oxidation of UL10 to UN10 that occurred during sample processing and analysis and thus permitted accurate adjustments of natively circulating Q10 levels.

All LPM measured were much lower in cord than in peripheral plasma. Cord plasma levels of total carotenoids, tocopherols, and retinol were approximately 10-fold, 3- to 5-fold and 1.5- to 3-fold lower than those in children or women. Cord plasma levels of total Q10 (TQ10; median, 113 ng/mL) were approximately 2-fold or 7- to 9-fold lower than peripheral plasma levels of neonates or children and adults, respectively. In contrast, the UN10/TQ10 ratio was substantially higher in cord (24%) than in peripheral plasma of children (3–4%) or adults (9%). Among the 5 ethnic groups in our cohort, no differences were observed in the levels of UN10, UL10, or TQ10. However, significant differences in many of the LPM were observed between ethnicities. More research is needed to explain these phenomena.     

Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases.

Coenzyme Q10 (CoQ10) is an essential cofactor of the electron transport chain as well as an important antioxidant. Previous studies have suggested that it may exert therapeutic effects in patients with known mitochondrial disorders. We investigated whether it can exert neuroprotective effects in a variety of animal models. We have demonstrated that CoQ10 can protect against striatal lesions produced by both malonate and 3-nitropropionic acid. It also protects against MPTP toxicity in mice. It extended survival in a transgenic mouse model of amyotrophic lateral sclerosis. We demonstrated that oral administration can increase plasma levels in patients with Parkinson's disease. Oral administration of CoQ10 significantly decreased elevated lactate levels in patients with Huntington's disease. These studies therefore raise the prospect that administration of CoQ10 may be useful for the treatment of neurodegenerative diseases.     

微生物法高产辅酶Q10的研究进展

辅酶Q10是呼吸链上的一种电子传递体,具有抗氧化功能.微生物法生产辅酶Q10具有产物活性高、原料成本低并可以通过规模放大提高生产能力等优点.综述了微生物法生产辅酶Q10的生产菌种,以及能够提高辅酶Q10产量的各种不同的方法策略.     

辅酶Q10的生物合成及其高表达研究进展

辅酶Q10(CoQ10)不仅是呼吸链上的电子传递体,同时也具有抗氧化功能。目前全球市场上的CoQ10正处于一种供不应求的状态。我们简要论述了CoQ10的结构、性质、功能及其生物合成过程,同时概括总结了现阶段为提高CoQ10产量而采用的新型技术手段。