生物活性

Coenzyme Q10 is an electron transport chain component of the mitochondria, which assists proton and electron transfer across the inner mitochondrial membrane. Displays neuroprotective activity. Studies indicate that Coenzyme Q10 can protect human endothelial cells from oxidative damage by modulating the nitric oxide pathway. Component of the mitochondrial transporter chain that behaves as a powerful antioxidant. In addition, Coenzyme Q10 inhibits LDL oxidation, a major process in the development of atherosclerosis. Coenzyme Q10 is known to suppress the down regulation of NOS3 (endothelial nitric oxide synthase, eNOS) and up-regulation of NOS2 (inducible nitric oxide synthase, iNOS). As a result of its ability to bind Ca2+, Coenzyme Q10 can transport this cation across artificial biomimetic membranes.

体外研究

体内研究

激酶实验

细胞实验

Cell culture, transfection and drug treatment[1]

PC12 cells were grown in Dulbecco’smodified Eagle’s medium (DMEM) supplemented with 100μg/mL penicillin/streptomycin,2 mM L-glutamine, 10% fetal bovine serum and maintained at 37°C, 5% CO₂ in a humidified incubator.

The expression vector pcDNA encoding human full-lengthATX3 was used for transfection. Constructs of normal ATX3 (pcDNA3-myc-ATX3-Q28)and expanded ATX3 (pcDNA3-myc-ATX3-Q84).

For transient transfections, cells were seededon 6-well plates and grown to 60–80% confluence for 16 h. For each well, cellswere exposed for 5 h to a mixture of 10μLLipofectAMINE 2000 Reagentt and 2μg of plasmid DNA in OptiMEM. Then,the culture medium was replaced by complete medium containing distinct drugs.Cells were incubated for another 48 h and examined. Drug treatments included 2.5,5 or 7.5 mM lithium carbonate and 10, 30, or 90μM coenzymeQ10.

Cellviability and apoptosis

Cell viability was evaluated by the MTT,3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium assay. After 48 h of drugtreatment, the medium was replaced, MTT was added to the DMEM (0.3 mg/mL)followed by a 4-h incubation. Next, cells were washed with PBS, dye crystalswere dissolved in DMSO and the absorbance measured at 570 nm.

Apoptotic cells were detected using theApoTargett Annexin-V FITC Apoptosis Kit, which employs a fluorescein-labeledAnnexin-V in concert with propidium iodide (PI), following manufacturer’s recommendation.Samples were analyzed on a FACScalibur flow cytometer. For each sample, aminimum of 10,000 events were collected and analyzed using CELLQuest software. ThePI results were used to exclude necrotic cells from the evaluation ofapoptosis.

动物实验

Animails[2]

The study was performed on 84 С₅₇Вlmale mice weighting 22.4 ± 1.12 g bred in animal facility

Materialsand admonitions

Lewis lung carcinoma (LLC) was used as atumor model. LLC cells (5 x 10⁵ cells per animal) were transplantedsubcutaneously. The compounds (L-Arginine hydrocloride (L-Arg), CoQ10) wereadministered intraperitoneally daily for 10 days at low or high doses: LArg- 60and 360 mg/kg body weight; CoQ10- 0.2 and1.2 mg/kg body weight.

Experiments

The animals were distributed into 8experimental groups; І — intact animals (n = 10); ІІ — tumor control (n = 11);ІІІ and ІV — animals with tumors treated with high (n = 12) and low (n = 10) dosesof L-Arg, respectively; V та VІ — animals with tumors treated with high (n =10) and low (n = 10) doses of СоQ10, respectively; VІІ and VІІІ — animals withtumors treated with high (n = 10) and low (n = 10) doses of L-Arg and СоQ10, respectively. Animals of group II received dailyintraperitoneal injections of physiological saline at corresponding volume for10 days and served as a positive control.

The research of the electron transportchain in mitochondria, СоQ10 levels in mitochondria and free iron (FI) in tumorcells was performed by electron paramagnetic resonance (EPR) method withcomputerized spectrometer RE-1307 using the technology of low-temperature stabilizationof biological material (77 K). The rate of superoxide radical generation bymitochondria of cells was determined by EPR method using a spin trap(2,2,6,6,-tetrametyl-4-oxypiperidine) at the room temperature in a specialparamagnetic pure quartz cuvette. The level of NO in the tumor tissue wasinvestigated by EPR using the Spin Traps technology (spin trap-diethyldithiocarbamates) at the temperature of 77 K.

The activity of MMP-2 and -9 in tumortissue was determined by zymography method in polyacrylamide gel (with additionof gelatin as a substrate) based on SDS-electrophoresis of proteins. The tumorvolume was determined by the formula 1: V = (π/6) · D1 · D2 · D3, (1) where V —tumor volume (mm3); D1, D2, D3 — tumor length, width, and height. The number ofmetastases was counted, and their volume — by the formula 1. The antitumoractivity of the studied compounds was evaluated by tumor growth inhibition: G%= (vc−ve)/mk · 100%, (2) where G% — percentage of tumor growth inhibition byvolume; vc — average tumor volume in the control; ve — average tumor volume inthe study group.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Lopes-Ramos CM, Pereira TC, Dogini DB, Gilioli R, Lopes-Cendes I. Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease. Braz J Med Biol Res. 2016;49(12):e5805.
[2] Burlaka AP GI, Golotiuk VV, Vovk AV, Lukin SМ. Superoxide- and NO-dependent mechanisms of antitumor and antimetastatic effect of L-arginine hydrochloride and coenzyme Q10. Exp Oncol. 2016;38(1):31-35.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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