Presence Of Coenzyme Q10 Research Articles

The effect of Coenzyme Q10 on mitochondrial biogenesis in mouse ovarian follicles during in vitro culture.

The aim of this research was to investigate the effect of Coenzyme Q10 (CoQ10) on the expression of the Transcription Factor A Mitochondrial (Tfam) gene and mtDNA copy number in preantral follicles (PFs) of mice during in vitro culture. To conduct this experimental study, PFs were isolated from 14-day-old National Medical Research Institute mice and cultured in the presence of 50 µm CoQ10 for 12 days. On the 12th day, human chorionic gonadotropin was added to stimulate ovulation. The fundamental parameters, including preantral follicle developmental rate and oocyte maturation, were evaluated. Additionally, the Tfam gene expression and mtDNA copy number of granulosa cells and oocytes were assessed using the real-time polymerase chain reaction. The results revealed that CoQ10 significantly increased the diameter of PFs, survival rate, antrum formation, and metaphase II (MII) oocytes (P < 0.05). Moreover, in the CoQ10-treated groups, the Tfam gene expression in granulosa cells and oocytes increased considerably compared with the control group. The mtDNA copy number of granulosa cells and oocytes cultured in the presence of CoQ10 was substantially higher compared with the control groups (P < 0.05). The addition of CoQ10 to the culture medium enhances the developmental competence of PFs during in vitro culture by upregulating Tfam gene expression and increasing mtDNA copy number in oocyte and granulosa cells.

Expression of Apoptosis-Related Genes in Cultured Ovarian Tissue of Mouse in Presence of Coenzyme Q10.

Oxidative stress affects the development of ovarian follicles during in vitro culture thus applying an antioxidant is necessary. The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10) on the expression of apoptosis-related genes of mouse ovaries during in vitro culture. The immature mouse ovaries were cultured in the presence of 50 μM CoQ10 for 7 days. Histological examinations were performed and the 17 beta-estradiol concentration was measured on the seventh day of culture. The relative expression of Caspase 3, Bax, Bad, and Bcl 2 genes were investigated by real-time RT-PCR. The rates of normal follicles in the presence of CoQ10 was significantly increased compared to the control group. Also, in CoQ10-trated group a significant increase in the level of 17 beta-estradiol was seen compared to the control group. The mRNA expression of anti-apoptotic gene Bcl2 was significantly increased while the expression of pro-apoptotic genes (Caspase3, Bax and Bad) significantly declined in CoQ10 treated group compared to those of control group. The supplementation of the ovarian culture media with CoQ10 improved the follicular development through alteration in expression of apoptosis-related genes and stimulated the production of estradiol.

Nippon Shokubai participates in COI-NEXT led by the University of Tokyo to jointly develop an integrated agro-industrial GX technologies to contribute to increase food production and green chemical manufacturing

Coenzyme-Q10 (Co-Q10) is an indigenous lipophilic provitamin synthesized from precursors, mevalonate, and phenylalanine, by all human cells. The level of Co-Q10 gradually decreases in human cells with aging so it can be obtained from exogenous sources like fishes, vegetables, and dairy products. Co-Q10 is available in the form of oral tablets, capsules, and toothpaste. The recommended oral dose is 30 to 60 mg/day to prevent deficiency. Co-Q10 is found in two chemical states, ubiquinones the oxidized form and ubiquinol the reduced form. It was first isolated in 1957 from beef mitochondria, while in 1958 it was revealed that its chemical structure was 2, 3-dimethoxy-5-methyl-6-decaprenyl benzoquinone. Co-Q10 serves as an essential carrier for the electron transfer in the mitochondrial respiratory chain for the synthesis of ATP. Co-Q10 has countless beneficial activities on human body, but antioxidant effect is one of the most important among all. The antioxidant activity of Co-Q10 is attributed to its benzoquinone ring. Co-Q10 can both accept and donate electrons which prove it to be a good antioxidant. The antioxidant properties of Co-Q10 minimizes the chances of neurodegenerative diseases like Friedrich’s ataxia, cardiovascular diseases, migraine, diabetes mellitus, cancer, and autoimmune diseases like Parkinson’s disease, Alzheimer’s disease, and ulcerative colitis. Co-Q10 is used as hepatoprotective and immune system enhancer. Co-Q10 prevents the oxidation of DNA, proteins, lipids and lipoproteins and protect sand enhances the antioxidant activity of vitamins (vitamin C and E) and enzymes like glutathione, superoxide dismutase and catalase. Co-Q10 is the only antioxidant which is endogenously synthesized and is lipid-soluble. The antioxidant and free radical scavenging properties of Co-Q10 have been proved by researchers both by animal and successful human studies. These studies suggest that the presence of Co-Q10 is very important for normal functioning of human body, and thus we must eat diet rich in Co-Q10 in order to protect our body from oxidative stress and diseases caused by free radicals.

The Effect of Coenzyme Q10/Collagen Hydrogel on Bone Regeneration in Extraction Socket Prior to Implant Placement in Type II Diabetic Patients: A Randomized Controlled Clinical Trial.

Background: The healing of an extraction socket leads to alveolar ridge resorption that can hinder future implant placement and further rehabilitation with special concerns in diabetes mellitus. Coenzyme Q10 (CoQ10) has been developed as a new material for alveolar socket augmentation. The aim of this study was to investigate the effect of CoQ10 hydrogel on bone regeneration after extraction of mandibular teeth in Type II diabetic patients. Methods: This trial was registered under the number NCT05122299 and included eighteen patients. The hydrogel was first prepared and characterized. After tooth extraction, the hydrogel was placed in the extraction sockets. Bone formation was evaluated three months after tooth extraction. Results: The bone density was significantly higher in the CoQ10 group than the other two groups measured on cone beam computed tomography (CBCT). The relative gene expression of Runt-related transcription factor 2 (RUNX2) and Osteopontin (OPN) showed significant increase in the presence of CoQ10. Histomorphometry revealed significantly less fibrous tissue in the CoQ10 group in comparison to the control or collagen group. Conclusion: The local application of CoQ10 after tooth extraction provided a simple, inexpensive, yet effective treatment facilitating bone formation and healing in the extraction sockets of diabetic patients.

Coenzyme Q10 effects in neurological diseases.

Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).

Coenzyme Q10 effects in neurological diseases

Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).

Coenzyme Q10 protects isolated human blood cells from TiO2 nanoparticles induced oxidative/antioxidative imbalance, hemolysis, cytotoxicity, DNA damage and mitochondrial impairment.

TiO2 NPs have been investigated for their toxic potential and studies have reported their toxicity is due to generation of oxidative stress. In the present study, we investigated the toxicity of TiO2 NPs and explored the potential of well-known antioxidant coenzyme Q10 (CoQ10) in counteracting the NP-induced toxicity in isolated human blood cells. When the isolated blood cells were treated with varying concentrations of TiO2 NPs (25-100μg/ml), only 50μg/ml dose induced statistically significant hemolysis in erythrocytes and cytotoxicity in lymphocytes (p < 0.05). None of the concentrations induced any significant increase in platelet aggregation. To investigate the protective effect of CoQ10, we incubated the isolated blood cells with 50μg/ml of TiO2 NPs in the presence and absence of 25μM of CoQ10 for 3h. Hemolysis, oxidative stress, LDH leakage and ATPase enzyme activity were studied in erythrocytes; cytotoxic and DNA damaging potential of NPs were determined in lymphocytes, along with mitochondrial membrane potential (MMP) and ADP/ATP ratio. Hemolysis, generation of oxidative stress, LDH leakage and reduced ATPase activity were observed in the erythrocytes treated with NPs alone (50μg/ml), the results were statistically significant at p < 0.05. Oxidative stress was evident by increased levels of malonaldehyde, indicating lipid peroxidation and generation of reactive oxygen species including hydrogen peroxide, together with statistically significant decrease in the activities of catalase and superoxide dismutase and reduced glutathione levels. In the lymphocytes treated with NPs alone (50μg/ml), cytotoxicity in MTT assay and DNA damage in comet assay were observed; in addition, mitochondrial membrane potential collapsed and ADP/ATP ratio increased indicating mitochondrial function impairment. However, in the presence of CoQ10, hemolysis, oxidative stress and LDH leakage in the erythrocytes and lymphocyte cytotoxicity and DNA damage were drastically reduced, enzyme activities, MMP and ADP/ATP ratio were restored towards normal levels. TiO2 NPs induce cytotoxicity, damage DNA in lymphocytes, and induce oxidative/anti-oxidative imbalance in erythrocytes. Antioxidant CoQ10 protects erythrocytes and lymphocytes from toxicity induced by TiO2 NPs.

Coenzyme Q10 improves the in vitro maturation of oocytes exposed to the intrafollicular environment of patients on fertility treatment.

Objective:To evaluate the impact of patient follicular environment with oxidative stress on oocyte quality.Methods:Patients on fertility treatment with either advanced maternal age or endometriosis were asked to donate follicular fluid collected during ovum pick-up. Follicular fluid (FF) was added (20%, 10% and 5%; %V/V) to in vitro maturation (IVM) medium with mouse oocytes. Following maturation culture, the oocytes were assessed for meiosis reinitiation. In a second setup, coenzyme Q10 was added to culture medium with FF. In addition to assessing meiotic maturation, a subset of oocytes was assessed for spindle structure and chromosome alignment.Results:Supplementation of IVM medium with FF of patients of advanced maternal age (with or without antioxidants) did not have an effect on the maturation capacity of mouse oocytes. However, the addition of FF of individuals with endometriosis (without antioxidants) in the two highest concentrations affected oocyte maturation (61.5% & 57.0% maturation) compared with the lowest concentration (89.2% maturation) (p<0.05). Supplementation of medium with coenzyme Q10 did not improve the maturation rate of oocytes exposed to the FF of individuals with endometriosis (28.5±13.7%) (p<0.05). Nevertheless, preliminary analysis of spindle abnormality and chromosome alignment revealed that oocytes resuming meiosis in the presence of FF of patients with endometriosis displayed aberrant spindle morphology and chromosomal misalignment.Conclusion:The follicular environment of patients with endometriosis severely affected oocyte (nuclear) maturation. In vitro maturation in the presence of coenzyme Q10 appears to be a tool for rescuing oocytes exposed to such follicular environment.

Mechanistic Approach for Thioridazine-Induced Hepatotoxicity and Potential Benefits of Melatonin and/or Coenzyme Q10 on Freshly Isolated Rat Hepatocytes.

Thioridazine (TZ) is used mainly in the treatment of schizophrenia. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. In this context, we examined the cytotoxic mechanisms of TZ on freshly isolated rat hepatocytes to better understanding of the pathogenesis of TZ-induced hepatotoxicity. Hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein. The level of parameters such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosomal membrane integrity and cellular glutathione (GSH) content in TZ-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Coenzyme Q10 and/or melatonin. Results showed that TZ caused an increase in ROS formation as well as induction of LPO and GSH depletion. Moreover, mitochondria and lysosomes seem to be targets of TZ-induced toxicity. The administration of Coenzyme Q10 and/or melatonin efficiently decreased the rate of ROS formation, LPO and improved cell viability, MMP, GSH level and lysosome membrane integrity. This study proposes the possible protective role of Coenzyme Q10 and/or melatonin against TZ-induced cellular injury probably through their radical scavenging properties and their effects on mitochondria and lysosomes.

Mitochondrial dysfunction on sinoatrial node and pulmonary vein electrophysiological activities.

Atrial fibrillation (AF) is associated with mitochondrial dysfunction. Sinoatrial node (SAN) dysfunction increases arrhythmogenesis of pulmonary veins (PVs), which is the most important trigger of AF; however, it is not clear whether mitochondrial dysfunction differentially regulates electrical activity of SANs and PVs. In the present study, conventional microelectrodes were used to record the action potentials (APs) in isolated rabbit PVs, SANs, left atrium (LA) and right atrium (RA) before and after application of trifluorocarbonylcyanide phenylhydrazone (FCCP; a mitochondrial uncoupling agent) at 10, 100 and 300 nM. FCCP application at 100 and 300 nM decreased spontaneous rates in PVs and in SANs at 10, 100 and 300 nM. FCCP shortened the 20, 50 and 90% AP durations in the LA, and shortened only the 20% AP duration in the RA. FCCP caused a greater rate reduction in SANs than in PVs; however, in the presence of coenzyme-Q10 (10 µM), FCCP reduced the beating rate in PVs and SANs to a similar extent. In SAN-PV preparations with intact electrical connections, FCCP (100 nM) application shifted the SAN-PV electrical conduction into PV-SAN conduction in 5 (62.5%) of 8 preparations. In conclusion, mitochondrial dysfunction modulates PV and SAN electrical activities, which may contribute to atrial arrhythmogenesis.

Study of the Interaction Between Coenzyme Q10 and Human Serum Albumin: Spectroscopic Approach

UV–vis absorption, fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopic methods were employed to reveal the mechanism of the binding between coenzyme Q10 (CoQ10) and human serum albumin (HSA) under simulated physiological conditions (pH = 7.4). The binding parameters were calculated by the fluorescence quenching method. The results demonstrate that the fluorescence quenching of HSA by CoQ10 is mainly static quenching due to the formation of HSA–CoQ10 complexes, and the number of binding sites (n) is equal to 1. The thermodynamic parameters (ΔH 0 = −43.18 kJ·mol−1, ΔS 0 = −47.05 J·mol−1·K−1, ΔG 0 = −29.15 kJ·mol−1) indicate that the enthalpy-driven binding process is favorable, and the main binding forces between CoQ10 and HSA are hydrogen bonds and van der Waals forces. The competitive experiments using different site markers indicate that subdomain IIA (site I) of HSA is the primary binding site for CoQ10. The average binding distance (r) between HSA and CoQ10 is 4.29 nm, which was estimated according to the Forster’s theory of non-radiation energy transfer. In addition, the UV–vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid fluorescence, CD spectra, and FT-IR spectroscopy data show slight conformational changes of HSA in the presence of CoQ10. These findings provide valuable binding information between HSA and CoQ10, which may be beneficial to pharmacokinetics research and could be used to design the dosage form of CoQ10.

Encapsulation of coenzyme Q10 in a simple emulsion-based nutraceutical formulation and application in cheese manufacturing

Coenzyme Q10 (CoQ10) was encapsulated successfully in a nutraceutical formulation composed of calcium caseinate, flaxseed oil and lecithin. The effect of CoQ10 on the physico-chemical stability of emulsions was compared to emulsions without CoQ10. According to ATR-FTIR analysis, emulsions were found to be more stable in the presence of CoQ10. The emulsion with CoQ10 was used as a functional cream in the cheese making process. The retention rate of CoQ10, composition and cheese yield were also determined. Quantification of CoQ10 by HPLC showed that the retention of this lipophilic agent into cheese matrix was 93% and equivalent to the total lipid retention. Protein retention and cheese yield were not affected by the addition of the functional cream. For the first time, CoQ10 has been encapsulated in a cheese matrix, hence demonstrating that CoQ10 could be used in the development of functional cheeses.

Pharmacokinetic Interaction between Nifedipine and Coenzyme Q10 in Rats: A New Type of Drug-Supplement Interaction

We examined pharmacokinetic (PK) and pharmacodynamic (PD) interactions between coenzyme Q10 (CoQ10) and nifedipine (NFP), which is a popular medicine for treating hypertension, and elucidated possible mechanisms for the interaction between CoQ10 and NFP in rats. The mean plasma concentrations of NFP in rats after the oral administration of NFP (1 mg/kg) with CoQ10 (75 mg/kg) were increased over the study period and the area under the plasma concentration-time curve (AUC), showed a 1.47-fold increase compared with that of the control. Rats that received NFP with CoQ10 showed a continuous decrease in the mean blood pressure over the study period compared with the control. There were no significant changes in the PK parameters of NFP after intravenous administration (1 mg/kg) between with and without oral CoQ10 pretreatment, and also no significant changes in the intestinal excretion of rhodamine 123 (Rho123) or NFP between with and without CoQ10 were found. In contrast, the portal plasma concentration of NFP after intra loop administration in the presence of CoQ10 (75 mg/kg) showed a 1.6-fold increase in the AUC value compared with that of the control. As for physicochemical properties, the partition coefficient of NFP showed a marked increase in the presence of CoQ10 over 10 mg/ml in the organic phase (n-hexane). From on an analysis of the absorbance spectrum, CoQ10 showed a shift towards a longer wavelength in hydrophobic environments with NFP, suggesting that CoQ10 reacts with NFP to form a charge-transfer complex due to a pi-cloud between them. In conclusion, it was found that CoQ10 increases the oral bioavailability of NFP and that this interaction between NFP and CoQ10 is not caused by metabolism via cycochrome P450 (CYP) 3A in the liver or intestine or by the inhibition of P-glycoprotein function, by the physicochemical interaction between them. Therefore, the solubility of NFP in a hydrophobic environment could be enhanced by forming a chargetransfer complex with CoQ10, and it is considered that NFP deviating from a charge-transfer complex may migrate to the blood circulation from the intestinal tract. This mechanism of interaction is considered a new type of drugsupplement interaction.

Mechanisms of inhibitory effects of CoQ10 on UVB‐induced wrinkle formation in vitro and in vivo

Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species (ROS). ROS are thought to be a major factor to initiate the up-regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation. Coenzyme Q10 (CoQ10) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA-induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation-induced cytokine production in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB-induced IL-6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ10. Furthermore, MMP-1 production of fibroblasts cultured with the medium containing CoQ10 collected from UVB-irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ10 may inhibit the production of IL-6 which stimulate fibroblasts in dermis by paracrine manner to up-regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin.

Effect of analogs with modified prenyl side chains on growth of serum deficient HL60 cells.

This study was organized by Professor Karl Folkers with the objective of finding derivatives of coenzyme Q which could be more effectively absorbed and would give better biomedical effects. In this series all the compounds are 2,3 dimethoxy, 5 methyl p benzoquinone with modified side chains in the 6 position. The modifications are primarily changes in chain length, unsaturation, methyl groups and addition of terminal phenyl groups. The test system evaluates the growth of serum deficient HL60, 3T3 and HeLa cells in the presence of coenzyme Q10 or coenzyme Q analogs. Short chain coenzyme Q homologues such as coenzyme Q2 give poor growth but compounds with saturated short aliphatic side chains from C10 to C18 produce good growth. Introduction of a single double bond at the 2' or 8' position in the aliphatic chain retains growth stimulation at low concentration but introduces inhibition at higher concentration. Introduction of a 3' methyl group in addition to the 2' enyl site in the side chain decreases the growth response and maintains inhibition. Addition of a terminal phenyl group to the side chain from C5 to C10 can produce analogs which give strong stimulation or strong inhibition of growth. The action of the analogs is in addition to the natural coenzyme Q in the cell and is not based on restoration of activity after depletion of normal coenzyme Q. The effects may be based on any of the sites in the cell where coenzyme Q functions. For example, coenzyme Q2 is known to decrease mitochondrial membrane potential whereas the analog with a 10C aliphatic side chain increases potential. Both of these compounds stimulate plasma membrane electron transport. Inhibition of apoptosis by coenzyme Q may also increase net cell proliferation and the 10C analog inhibits the permeability transition pore.

Electron transport chain of Zymomonas mobilis

The interaction of the membrane-bound glucose dehydrogenase from the anaerobic but aerotolerant bacterium Zymomonas mobilis with components of the electron transport chain has been studied. Cytoplasmic membranes showed reduction of oxygen to water with the substrates glucose or NADH. The effects of the respiratory chain inhibitors piericidin, capsaicin, rotenone, antimycin, myxothiazol, HQNO, and stigmatellin on the oxygen comsumption rates in the presence of NADH or glucose as substrates indicated that a complete and in the most parts identical respiratory chain is participating in the glucose as well as in the NADH oxidation. Furthermore, the presence of coenzyme Q10 (ubiquinone 10) in Z. mobilis was demonstrated. Extraction from and reincorporation of the quinone into the membranes revealed that ubiquinone is essential for the respiratory activity with glucose and NADH. In addition, a membrane-associated tetramethyl-p-phenylene-diamine-oxidase activity could be detected in Z. mobilis.

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It is said that Coenzyme Q10 augments the inhibition of DNA synthesis of cultured mouse sarcoma cells (Meth A cell) produced by Adriamycin in a dose dependent manner.To elucidate this enhancing mechanism, we analyzed the intracellular concentrations of Adriamycin in Meth A cells and Swiss albino 3T6 immortalized cells by flowcytometry techniques. In Meth A cells, a large part of Adriamycin's action is due to an active transport system, especially in influx. The intracellular concentration of Adriamycin rises with increasing doses of Coenzyme Q10. Thus, the augmenting antitumor effect of Coenzyme Q10 depends on its rapid increase and on the maintenance of a high intracellular concentration of Adriamycin. On the contrary in 3T6 cells, the level of Adriamycin decreases with increasing doses of Coenzyme Q10, because active efflux is more enhanced by the presence of Coenzyme Q10 than active influx, while passive influx and active efflux are the main actions of Adriamycin in the usual state without Coenzyme Q10.It is concluded that Coenzyme Q10 plays an opposite role in tumor cells and normal cells by the different way and it affects the transport mechanism of Adriamycin. These findings suggest that combination chemotherapy with Coenzyme Q10 and Adriamycin is more effective, not only because it prevents adverse reactions such as cardiopathy, but also because it augments the anticancer effect of Adriamycin.

Effects of coenzyme Q10 and menadione on succinic dehydrogenase activity as measured by tetrazolium salt reduction.

Coenzyme Q10 and menadione have been shown to enhance the succinic dehydrogenase activity of rat liver homogenates and frozen sections as measured quantitatively by the reduction of INT. Increased formazan deposition as estimated by visual examination was also found in sections of liver and other tissues in comparable experiments with the two quinones in which the tetrazolium salt Nitro-BT was employed. Extraction of sections with acetone decreased the succinic dehydrogenase activity of liver sections by approximately two-thirds of that present in nonextracted sections as measured by INT reduction. The addition of coenzyme Q10 or menadione restored the activity to essentially that present in nonextracted sections incubated in the presence of the same constituents. These data suggest that a quinone, presumably coenzyme Q10, acts as an intermediate electron transport agent between succinic dehydrogenase and INT or Nitro-BT. The effects of coenzyme Q10 and menadione on the activities of diphosphopyridine nucleotide (DPNH) diaphorase, triphosphopyridine nucleotide (TPNH) diaphorase, α-glycerophosphate dehydrogenase and monoamine oxidase, all of which are demonstrable by tetrazolium salt reduction procedures, have been studied. Two of these enzymes, TPNH diaphorase and monoamine oxidase, show no significant enhancement of activity in the presence of coenzyme Q10, and a relatively slight enhancement in the presence of menadione. α-Glycerophosphate dehydrogenase shows a pattern of enhancement comparable to that of succinic dehydrogenase. DPNH diaphorase activity, while enhanced by both of the quinones, shows a lesser degree than is found with the succinic dehydrogenase and α-glycerophosphate dehydrogenase systems. The diverse effects of coenzyme Q10 and menadione on the five enzyme systems investigated in the present work indicate that the two quinones do not simply act as nonspecific intermediate electron carriers between dehydrogenase system and tetrazolium salt, but that they enhance enzyme activity by a more specific interaction with some component of the enzyme system.