The effect of coenzyme Q10 on the action of phospholipase

Using dimyristoyl L-alpha-phosphatidylcholine as a substrate, the effect of coenzyme Q10 on phospholipid digestion by phospholipase A2 and phospholipase C was investigated. Free myristic acids released by phospholipase A2, and myristic acids of dimyristoyl glyceride released by phospholipase C were methylated and determined quantitatively by gas-chromatography. Phospholipase A2 or phospholipase C released myristic acids dose-dependently from the substrate. Coenzyme Q10 prevented dose-dependently the hydrolysis of the substrate caused by phospholipase. These results suggest that pharmacological action of coenzyme Q10 could be attributed to its protection of membrane phospholipids against the attack of phospholipases.     

Therapeutic effect of coenzyme Q10 against experimentally-induced hepatocellular carcinoma in rats

The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5 g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4 mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis.     

The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline

Interaction of a drug with other drugs and dietary supplements is becoming an emerging issue for patients and health insurance authorities due to awareness of adverse drug event. In this study, we examined the effects of coenzyme Q10 (CoQ10), one of the most popular dietary supplements, on the pharmacokinetic parameters of theophylline in rats. The pharmacokinetic parameters of theophylline changed significantly when the drug was administered after five consecutive days of pretreatment with CoQ10. Time to reach maximum plasma concentration of theophylline delayed when the drug was administered after the pretreatment with CoQ10. Maximum plasma concentration and area under the curve of theophylline were about two-fold increased and other pharmacokinetic parameters such as half-life and volume of distribution were also changed significantly. Therefore, although CoQ10 is generally considered a safe dietary supplement, it appears that patients on theophylline therapy should use caution when they take CoQ10.     

Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations

Importance of the field: Coenzyme Q₁₀ (CoQ₁₀) is found in blood and in all organs. CoQ₁₀ deficiencies are due to autosomal recessive mutations, ageing-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer and muscular and cardiovascular diseases have been associated with low CoQ₁₀ levels, as well as different ataxias and encephalomyopathies.

Areas covered in this review: We review the efficacy of a variety of commercial formulations which have been developed to solubilise CoQ₁₀ and promote its better absorption in vivo, and its use in the therapy of pathologies associated with low CoQ₁₀ levels, with emphasis in the results of the clinical trials. Also, we review the use of its analogues idebenone and MitoQ^®.

What the reader will gain: This review covers the most relevant aspects related with the therapeutic use of CoQ₁₀, including existing formulations and their effects on its bioavailability.

Take home message: CoQ₁₀ does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ₁₀ absorption. Oral CoQ₁₀ is a viable antioxidant strategy in many diseases, providing a significant to mild symptomatic benefit. Idebenone and MitoQ are promising substitutive CoQ₁₀-related drugs which are well tolerated and safe.     

Effective treatment with coenzyme Q10 of patients with chronic myocardial disease

Nineteen patients with chronic myocardial disease (NYHA Classes III and IV) were given Coenzyme Q10 in a controlled double-blind cross-over study. All had either low or borderline levels of CoQ10 in their blood, and showed a significant change into the normal range with oral CoQ10 replacement. Eighteen patients reported improvement in activity tolerance with replacement therapy. Combined clinical observations, stroke volume measured by impedance cardiography, and ejection fractions calculated from systolic time intervals, all showed significant improvement in parallel with CoQ10 administration. This application of the principles of bioenergetics introduces a promising new dimension to the study and treatment of the complex problem of myocardial failure.     

Hepatoprotective effect of coenzyme Q10 in rats with acetaminophen toxicity

The potential protective effect of coenzyme Q10 against acute liver injury induced by a single dose of acetaminophen (700 mg/kg, p.o.) was investigated in rats. Coenzyme Q10 treatment was given as two i.p. injections, 10 mg/kg each, at 1 and 12 h following acetaminophen administration. Coenzyme Q10 significantly reduced the levels of serum aminotransferases, suppressed lipid peroxidation, prevented the decreases of reduced glutathione and catalase activity, decreased the elevations of tumor necrosis factor-α and nitric oxide as well as attenuating the reductions of selenium and zinc ions in liver tissue resulting from acetaminophen administration. Histopathological liver tissue damage mediated by acetaminophen was ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the acetaminophen-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in liver tissue. It was concluded that coenzyme Q10 protects rat liver against acute acetaminophen hepatotoxicity, most probably through its antioxidant, anti-inflammatory and antiapoptotic effects.     

Survival effect of coenzyme Q10 and naloxone on experimental stroke gerbils

Coenzyme Q10 (CoQ10) and the opiate antagonist naloxone were compared as to their effect on the survival of mongolian gerbils with unilateral carotid ligation-induced stroke. Without medication all of the stroke gerbils died within 28 hours, but with a subcutaneous implantation of a 10 mg pellet of naloxone, 20% of the gerbils lived for 4 weeks. When a 250 mg pellet of CoQ10 was implanted subcutaneously, a definite effect on survival was observed, with 45% of the stroke gerbils living for 4 weeks. Considering that the action mechanisms of CoQ10 and naloxone are different, the combined use of these drugs in the treatment of stroke needs to be investigated.     

Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure

Coenzyme Q10 (CoQ10) treatment, orally administered as 100 mg daily dose, was initiated in a series of patients with advanced heart failure in an open, controlled design. They were all showing an insufficient response to classical therapy with diuretics and digitalis. Twelve patients with various causes of heart failure, classified clinically by echocardiography (ECHO), (12/12), and heart catheterization with endomyocardial biopsy, (10/12), were followed prospectively for a mean period of seven months. Serial assessments: Clinical examination (with questionnaire), ECG, chest X-ray, ECHO, systolic time intervals (STI) and blood levels of CoQ10 were performed. With a mean latency period of 30 days, eight out of 12 patients (67%) showed definite clinical improvement. Subjectively, the patients felt less tired, their general activity tolerance increased and dyspnoea at rest disappeared. There were obvious signs of decreased right-sided stasis (hepatic congestion). The heart rate fell significantly, and the heart volume (chest X-ray) decreased in the eight responders (although n.s.). A significant reduction in the left atrial size (ECHO) was registered, suggesting a reduced preload of the left ventricle, Furthermore, a significant decline in the PEP/LVET ratio (STI) was indicative of an improved myocardial performance. Preliminary CoQ10 withdrawal results showed severe clinical relapse with subsequent improvement on CoQ10 reinstatement, supporting the interpretation that treatment of these patients corrected a myocardial deficiency of CoQ10 and increased contractility. Hence CoQ10 appears to be an effective therapeutic agent in advanced cases of heart failure. This is an attractive circumvention of the traditional principles of therapy: supporting the myocardium directly by ameliorating a supposed underlying mitochondrial dysfunction (exhausted bioenergetics).     

Effect of coenzyme Q10 on hemodynamic response to ocular timolol

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial membrane and plays an important role in the maintenance of normal cardiac function. To evaluate the effects of ocular timolol on the cardiovascular system and determine the protective effect of CoQ10, 16 patients with glaucoma were studied using impedance cardiography. Following instillation of 1 mg timolol maleate in each eye, heart rate (HR) and stroke index (SI) decreased, and total peripheral resistance index (TPRI) increased significantly. Reexamination was performed after 6 weeks of 90 mg oral CoQ10. Despite decreases in HR, percent changes in HR were significantly less after CoQ10 at 120 min. Stroke index showed an initial increase which was not observed without CoQ10. These data suggest that CoQ10 delayed the appearance of inotropic blockade of timolol and hastened the disappearance of chronotropic blockade. Additional study of six normal volunteers with 6 weeks of oral CoQ10 showed a similar decrease of intraocular pressure after timolol instillation as compared to those without CoQ10. Thus, administration of oral CoQ10 in patients receiving ocular timolol may be useful in mitigating cardiovascular side effects without affecting intraocular pressure in the treatment of glaucoma.     

辅酶Q10对他汀类药物引起肌病的影响

羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶抑制剂即他汀类药物,目前临床广泛用于高血脂症的治疗.他汀类药物引起的不良反应肌病越来越受到关注.辅酶Q10(CoQ10)的缺乏则是引起肌病的重要原因,而他汀药物可能通过抑制CoQ10的合成及转运,减少血液循环中的CoQ10,对肌肉组织和线粒体中CoQ10的水平也有一定影响.试验证明,CoQ10和他汀类药物联合使用可以缓解他汀类药物引起的肌痛症状.文中综述了他汀类药物对血液循环和肌肉组织中CoQ10影响、他汀类药物对线粒体损伤及联用CoQ10后缓解他汀类药物引起的肌痛的研究进展.     

Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis

Purpose

Given the increased incidence of ulcerative colitis worldwide, the current study was designed to investigate the coloprotective potential of CoQ10 against experimentally induced ulcerative colitis (UC) and specify the implicated mechanisms.

Methods

Ulcerative colitis was induced by intracolonic instillation of [2 ml, 3% v/v acetic acid (AA)]. Rats in the different experimental groups received CoQ10 (10 or 30 and 100 mg/kg, orally) for eight consecutive days, either in a protective or curative regimen.

Results

Intracolonic AA instillation significantly increased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein and decreased the serum total antioxidant capacity. Colon MDA, TNF-α and calcium content significantly increased as well, with concomitant reduction in colon GSH, SOD, CAT, Nrf2 and HO-1 contents. Moreover, immunohistochemical staining of colon specimen revealed increased expression of caspase-3 with significant histopathological changes. Coenzyme Q10 suppressed the release of inflammatory biomarkers and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, CoQ10 significantly decreased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein, colon MDA, TNF-α, caspase-3 expression and increased the serum total antioxidant capacity. Colon GSH, SOD, CAT, Nrf2 and HO-1 contents significantly increased. Moreover, coenzyme Q10 significantly preserved tissue histopathological architecture. It appears that the coloprotective effect of CoQ10 was calcium-independent.

Conclusion

Coenzyme Q10 dose-dependently protects against AA-induced UC mainly via modulation of Nrf2/HO-1 and caspase-3 pathways. Antioxidant, anti-inflammatory and anti-apoptotic properties of CoQ10 are implicated in its observed therapeutic benefit.

     

辅酶Q_(10)微生物发酵生产的研究进展

利用微生物发酵生产的辅酶Q10(CoQ10)产物活性好,并可通过诱变育种和优化工艺大幅度提高生产能力。文章综述菌种的突变育种、发酵工艺的优化。     

206例胸闷患者病因分析及辅酶Q10治疗效果评价

目的：探讨胸闷患者的常见病因,并评价辅酶Q10对缓解胸闷症状治疗效果。方法选择2010年9月～2013年1月间住院的无心肺病史胸闷患者206例,随机分为治疗组和对照组,在常规治疗基础上,对照组患者口服维生素C片、治疗组口服辅酶Q10治疗。对患者临床表现及检查结果进行分析。结果胸闷患者的病因主要有：冠脉慢血流现象、慢性阻塞性肺疾病、支气管哮喘、冠心病、气胸、急性上呼吸道感染、胸腔积液、肺炎、心律失常、肺癌、心肌炎等。治疗组胸闷症状明显改善（Z＝2.197,P＝0.028）。结论无心肺病史胸闷患者发病主要原因为冠脉慢血流现象及慢性阻塞性肺疾病,在诊断明确前辅酶Q10有助于安全缓解症状。     

Isotachophoretic evidence for energy-preservating effect of coenzyme Q10 on isolated guinea-pig cardiac muscle

Effects of coenzyme Q10 (CoQ10) on hypoxia-induced changes in ATP, NAD and NADH levels were studied in the isolated atrial and ventricular muscles of guinea-pigs. Guinea-pigs were pretreated with CoQ10 (60 mg/kg/day, i.p.) or the solvent for 3 consecutive days before initiation of study. The concentrations of ATP, NAD and NADH were determined by isotachophoresis. The concentrations of ATP and NAD contained in the atrial or ventricular muscle decreased with increasing incubation time with hypoxic Tyrode's solution (pO2 not equal to 160 mmHG), but that of NADH increased. However, the ATP and NAD concentrations of atrial and ventricular muscles from CoQ10-pretreated animals tended to be higher than those from solvent-pretreated ones. Moreover, the increase in NADH concentration during hypoxia tended to be less in the CoQ10-pretreated preparation than in the solvent-pretreated one. These results suggest that the pretreatment with CoQ10 leads to the increase in CoQ10 content in mitochondria of heart muscle, thereby permitting the improvement of oxidative phosphorylation in the mitochondria during hypoxia.     

Protective effect of coenzyme Q10 on erythrolysis induced by octoxinol or hypotonic salines

Using dog erythrocytes, the effect of coenzyme Q10 (CoQ10) on the resistance of the erythrocyte membrane was investigated. Hemolysis was induced either by Octoxinol (Triton X-100) a well-known detergent, or by hypotonic salines. Although no detectable CoQ10 was observed in erythrocyte without CoQ10 addition, the increment in CoQ10 content in erythrocyte was found to be proportional to the doses of CoQ10 added to the erythrocyte samples. Administration of CoQ10 inhibited significantly the hemolysis induced either by octoxinol or hypotonic salines by a dose-dependent manner. These results suggest that CoQ10 incorporated into the erythrocyte increased the resistance of erythrocyte membrane by a direct structural effect on the membrane.     

Synthesis of deuterium‐labelled coenzyme Q10

Deuterium‐labelled coenzyme Q₁₀ ([2‐CD₃‐1′‐CD₂]coenzyme Q₁₀, coenzyme Q₁₀‐d₅ ) was synthesized by condensation of 2,3‐dimethoxy‐[5‐CD₃]methyl‐1, 4‐hydroquinone with [1‐CD₂]decaprenol. Five positions were selected for deuteration as replacement at these positions allowed examination of every step of the synthesis. This examination was carried out by a combination of ¹H‐ and ¹³C‐nuclear magnetic spectrometry and mass spectrometry. Further, these positions have been proved to be metabolically stable. This reagent makes simultaneous quantification of the source of coenzyme Q₁₀ (exogenously supplied or endogenously supplied) possible in biological samples by measurements on gas chromatography–mass spectrometry. Copyright © 2002 John Wiley & Sons, Ltd.     

The effect of HMG-CoA reductase inhibitors on coenzyme Q10: possible biochemical/clinical implications.

The HMG-CoA reductase inhibitors, also known as statins, have an enviable safety profile; however, myotoxicity and to a lesser extent hepatotoxicity have been noted in some patients following treatment. Statins target several tissues, depending upon their lipophilicity, where they competitively inhibit HMG-CoA reductase, the rate-limiting enzyme for mevalonic acid synthesis and subsequently cholesterol biosynthesis. HMG-CoA reductase is also the first committed rate-limiting step for the synthesis of a range of other compounds including steroid hormones and ubidecarenone (ubiquinone), otherwise known as coenzyme Q(10) (CoQ(10)). Recent interest has focused on the possible role CoQ(10) deficiency may have in the pathophysiology of the rare adverse effects of statin treatment. Currently, there is insufficient evidence from human studies to link statin therapy unequivocally to pathologically significantly decreased tissue CoQ(10) levels. Although statin treatment has been reported to lower plasma/serum CoQ(10) status, few human studies have assessed tissue CoQ(10) status. The plasma/serum CoQ(10) level is influenced by a number of physiological factors and, therefore, has limited value as a means of assessing intracellular CoQ(10) status. In those limited studies that have assessed the effect of statin treatment upon tissue CoQ(10) levels, none have shown evidence of a fall in CoQ(10) levels. This may reflect the doses of statins used, since many appear to have been used at doses below those recommended for their maximum therapeutic effects. Moreover, the poor bioavailability in those peripheral tissues tested may not reflect the effects the agents are having in liver and muscle, the tissues commonly affected in those patients who do not tolerate statins. This article reviews the biochemistry of CoQ(10), its role in cellular metabolism and the available evidence linking possible CoQ(10) deficiency to statin therapy.     

辅酶Q_(10)的生物合成途径及发酵工艺优化

辅酶Q10作为生物体有氧呼吸链中不可缺少的电子递氢体,广泛应用于生物医药、化妆品和保健品等领域。微生物发酵法生产辅酶Q10具有产物活性高、原料成本低等优点。此文对辅酶Q10的生物合成途径和发酵工艺优化进行了综述。     

HPLC测定辅酶Q_(10)软胶囊中的主药并检查有关物质

目的建立测定软胶囊中辅酶Q10的含量及有关物质检查的方法。方法采用硅胶吸附HPLC法,色谱柱为TianheKromasil Silica(250 mm×4.6 mm,5μm),流动相为正己烷-正丁醇(99.2:0.8),柱温为35℃。结果辅酶Q10进样量1.320~6.032μg与峰面积的线性关系良好(r=0.9993),分析方法精密度的RSD=0.42%;辅酶Q10的最低检出限为0.57 ng(S/N=3)。结论所建方法简便、灵敏、准确,可用于辅酶Q10的含量测定及有关物质的检查。     

L-carnitine and coenzyme Q10 protective action against ischaemia and reperfusion of working rat heart.

The protective effect of L-carnitine, coenzyme Q10 and their combination on haemodynamic and metabolic variables has been investigated in isolated perfused working rat hearts after 10 min of global normothermic ischaemia followed by 60 min of reperfusion. In untreated rats or in rats treated only with L-carnitine or with coenzyme Q10, this experimental condition did not induce any irreversible myocardial injury as measured by leakage of cardiac enzymes; however, it decreased some haemodynamic parameters such as cardiac output and minute work, as well as the ATP concentration and the total adenine nucleotide pool. No variations in haemodynamic and metabolic parameters were observed in the rats treated with L-carnitine plus coenzyme Q10. In the perfusate of the hearts of the rats treated with both compounds, a lower purine release (a good index of myocardial energy balance) was also obtained. Although the molecular mechanisms remain to be defined, it appears that the association of L-carnitine and coenzyme Q10 is more effective than using these compounds separately. The complementary and synergic actions of L-carnitine and coenzyme Q10 on metabolism and against peroxidation by oxygen reaction species may explain the efficacy of their association.