Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

Background: Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.Methodology/Principal Findings: To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 mu M of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.Conclusions/Significance: These results indicate that: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present

Chronic kidney disease and coenzyme Q10 supplementation

Among the potential causes of chronic kidney disease (CKD), mitochondrial respiratory chain (MRC) dysfunction, oxidative stress and inflammation have been implicated as contributor factors to the pathogenesis of this disorder. It is thought that CoQ10 supplementation may offer some therapeutic potential in the treatment of patients with CKD, since CoQ10 has a key role in normal MRC function, as well as having antioxidant and anti-inflammatory action. This article will outline the current knowledge on the use of CoQ10 in the treatment of CK

Evaluation of quick disintegrating calcium carbonate tablets

The purpose of this investigation was to develop a rapidly disintegrating calcium carbonate (CC) tablet by direct compression and compare it with commercially available calcium tablets. CC tablets were formulated on a Carver press using 3 different forms of CC direct compressed granules (Cal-Carb 4450®, Cal-Carb 4457®, and Cal-Carb 4462®). The breaking strength was measured using a Stokes-Monsanto hardness tester. The disintegration and dissolution properties of the tablets were studied using USP methodology. The calcium concentration was determined by an atomic absorption spectrophotometer. Scanning electron microscopy was used to evaluate the surface topography of the granules and tablets. Breaking strength of Cal-Carb 4450®, Cal-Carb 4457®, and Cal-Carb 4462® tablets was in the range of 7.2 to 7.7 kg, as compared with a hardness of 6.2 kg and 10 kg for the commercially available calcium tablets Citracal® and Tums®, respectively. The disintegration time for the tablets presented in the order earlier was 4.1, 2.1, 1.9, 2.9, and 9.7 minutes, respectively. The dissolution studies showed that all formulations released 100% of the elemental calcium in simulated gastric fluid in less than 20 minutes. In summary, this study clearly demonstrated that quick disintegrating CC tablets can be formulated without expensive effervescence technology