coenzyme-q10 and Leukemia

It was clinically evaluated by double blind method whether co-enzyme Q10 has protective effects on hair loss caused by anthracycline antibiotics. Six cases of acute leukemia, 2 blastic crisis of CML and 11 malignant lymphoma were entered to this study. DCMP regimen for acute leukemia for VEPA for lymphoma were performed. Coenzyme Q10 (or placebo) of 120 mg/day was orally administered. The grade of hair loss was classified into five groups. Five cases were only given to DM and 3 cases receiving DM and CoQ10. ADM was 6 cases and 5 were combined with CoQ10. No significant diffehence in effect of CoQ10 administration rence was recognized between two groups statistically. Elevations of GOT and GPT were less frequent in the group receiving CoQ10.

Topics: Adult; Aged; Alopecia; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Coenzymes; Double-Blind Method; Female; Humans; Leukemia; Male; Middle Aged; Naphthacenes; Ubiquinone

The effect of the alkyl side chain length of coenzyme Q10 on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained provide guidance for the design of CoQ10 analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent.

Topics: Animals; Cattle; Cell Line; Cell Line, Tumor; Cytoprotection; Electron Transport; Humans; Leukemia; Membrane Potential, Mitochondrial; Mitochondria; Oxygen Consumption; Reactive Oxygen Species; Retinal Ganglion Cells; Structure-Activity Relationship; Ubiquinone

UV-C radiation is able to impair cellular functions by directly damaging DNA, and by inducing an increased formation of reactive oxygen species that leads to a condition of oxidative stress. In this study we evaluated different responses to UV insult of two leukemia cell lines, HL-60 and Raji, and the relationship with their CoQ10 content. DNA damage was monitored by means of the alkaline single cell gel electrophoresis (Comet assay); intracellular levels of ROS, mitochondrial depolarization and cell viability was measured by flow cytometry. Raji cells appeared more resistant to the UV insult; moreover, they did not show any increase in ROS content and the extent of mitochondrial depolarisation was much lower than in HL 60 cell line. Raji cells also contained significantly higher levels of CoQ10 and their ability to incorporate and to reduce exogenous CoQ10 added to the culture medium was remarkably elevated compared with HL 60.

Topics: Cell Survival; Coenzymes; DNA Damage; Electrophoresis, Agar Gel; HL-60 Cells; Humans; Leukemia; Membrane Potentials; Mitochondria; Oxidation-Reduction; Oxidative Stress; Propidium; Reactive Oxygen Species; Tumor Cells, Cultured; Ubiquinone; Ultraviolet Rays

Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects cell membranes from oxidative damage and decreases apoptosis in leukemic cells cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2 (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum withdrawal induced an early increase of neutral-sphingomyelinase activity, release of ceramide, and activation of caspase-3 in both cell lines, but this effect was more pronounced in CEM cells. CoQ10 prevented activation of this cascade of events. Lipids extracted from serum-depleted cultures activated caspase-3 independently of the presence of mitochondria in cell-free in vitro assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by okadaic acid, indicating the implication of a phosphatase in this process. Our results support the hypothesis that plasma membrane CoQ10 regulate the initiation phase of serum withdrawal-induced apoptosis by preventing oxidative damage and thus avoiding activation of downstream effectors as neutral-sphingomyelinase and subsequent ceramide release and caspase activation pathways.

Topics: Apoptosis; Caspase 3; Caspase Inhibitors; Cell Membrane; Cell-Free System; Ceramides; Coenzymes; Culture Media, Serum-Free; Electron Transport Complex IV; Enzyme Activation; Humans; Leukemia; Lipid Metabolism; Mitochondria; Okadaic Acid; Oxidative Stress; Sphingomyelin Phosphodiesterase; Time Factors; Tumor Cells, Cultured; Ubiquinone

Adriamycin (ADR), one of the anthracycline derivatives, has the most strong cardiotoxicity. We studied the cardiotoxicity caused by ADR in New Zealand white rabbits and its protection by the medication of CoQ10. The findings of ECG and the myocardial tissue examined by the electron microscope showed the effectiveness of the injection of CoQ10 to prevent the cardiotoxicity caused by ADR. The concomitant injection of CoQ10 dissolved in saline was tried in patients with various kinds of neoplasm who were given more than 200 mg of ADR or DM. Only one patient showed the ST-T change. On the contrary, 3 of patients given more than 200 mg ADR or DM alone showed abnormal change of ECG.

Topics: Acute Disease; Adult; Aged; Animals; Arrhythmias, Cardiac; Cardiomyopathies; Coenzymes; Doxorubicin; Electrocardiography; Female; Heart; Humans; Leukemia; Lymphoma; Male; Middle Aged; Rabbits; Ubiquinone

Cardiotoxicity induced by adriamycin and protective effect by coenzyme Q10 were studied in 80 closely-followed patients receiving chemotherapy with adriamycin. Serial electrocardiograms were recorded immediately before and after the administration of adriamycin each times. The electrocardiographic parameters (heart rate, P-Q duration, QRS-duration, QRS voltage and QTc-duration) were analyzed. In patients treated with adriamycin alone, QTc-duration was prolonged significantly. On the other hand, in patients treated with adriamycin plus coenzyme Q10, QTc-duration was not significantly prolonged. This Suggests that coenzyme Q10 may reduce negative inotropic action induced by adriamycin. Further, the QRS voltage was also significantly decreased in patients treated with adriamycin alone, but was not decreased in patients treated with adriamycin plus coenzyme Q10. These findings suggest that some electrocardiographic changes due to adriamycin may be prevented by coenzyme Q10.

Topics: Coenzymes; Doxorubicin; Electrocardiography; Female; Gastrointestinal Neoplasms; Heart; Heart Rate; Humans; Leukemia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Time Factors; Ubiquinone

This study was designed to evaluate the usefulness of Coenzyme Q10 (CoQ10) in the prevention of side effects due to anthracycline agents-Adriamycin (ADM) and Daunorubicin (DNR)-by comparing the preventive effect between CoQ10-treated and non-treated groups. The subjects were 79 patients, 55 of whom had malignant lymphoma. The age range was from 16 to 77 years with a mean age of 45.4 years. CoQ10 was administered by intravenous drip at 1 mg/kg/day the day before ADM or DNR administration, on the day and for a further 2 days after administration. In mean total dose, complete remission rate and mortality, no significant differences were observed between the 2 groups. Although there were also no significant differences in the degree of alopecia, fever, nausea and vomiting, the incidences of diarrhea and stomatitis were significantly (p less than 0.10 and p less than 0.05, respectively) reduced in the CoQ10-treated group. Depression of ST waves (more than 0.05 mV) and changes in T waves (R/10 greater than T, flat, inversion) on ECG were regarded as a parameter of aggravation. Such ECG aggravation was found in 20 of 40 patients given CoQ10 (50.0%) and in 18 of 25 receiving none (72.0%); a cardiotoxicity-inhibiting tendency was thus evident (p less than 0.10). In heart rate, tachycardia was noted in the nontreated group when the period of use of anthracycline agents exceeded 8 weeks. Twenty nine patients received ADM or DNR for 8 weeks or more, and, of them, 17 were treated with CoQ10; 11 of the 17 (64.7%) showed ECG aggravation, while 11 of 12 patients (91.7%) not treated with CoQ10 showed ECG aggravation. A tendency to depress ECG aggravation was thus observed in the treated group (p less than 0.10).

Topics: Adolescent; Adult; Aged; Alopecia; Anorexia; Coenzymes; Daunorubicin; Diarrhea; Doxorubicin; Drug Therapy, Combination; Electrocardiography; Female; Fever; Heart Rate; Humans; Leukemia; Male; Middle Aged; Nausea; Stomatitis; Ubiquinone