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Uptake of dietary coenzyme Q supplement is limited in rats
Abstract
Coenzyme Q is an important mitochondrial redox component and the only endogenously produced lipid-soluble antioxidant. Its tissue concentration decreases with aging and in a number of diseases; dietary supplementation of this lipid would fulfill important functions by counteracting coenzyme Q depletion. To investigate possible uptake, rats were administered 12 mumol coenzyme Q10/100 g body wt once daily by gastric intubation. The appearance of coenzyme Q10 in various tissues and blood after 6 h, 4 d or 8 d was studied. The control group of rats received rapeseed-soybean oil (the vehicle in the experimental group). Lipids were extracted with petroleum ethermethanol, and the reduced and oxidized forms of coenzyme Q9 and Q10 were separated and quantified by reversed-phase HPLC. In the plasma, the total coenzyme Q concentration was doubled after 4 d of treatment. Coenzyme Q10 was also recovered in liver homogenates, where, as in the plasma, it was largely in the reduced form. Uptake into the spleen could be to a large extent accounted for by the blood content of this organ. No dietary coenzyme Q10 was recovered in the heart or kidney. The uptake in the whole body was 2-3% of the total dose. Coenzyme Q10 found in the liver was located mainly in the lysosomes. Dietary coenzyme Q10 did not influence the endogenous biosynthesis of coenzyme Q9. This is in contrast to dietary cholesterol, which down-regulates cholesterol biosynthesis. The dietary coenzyme Q10 level in the plasma decreased to approximately 50% after 4 d. These results suggest that dietary coenzyme Q10 may play a role primarily in the blood and that no appreciable uptake occurs into tissues.
... It is called coenzyme Q10 (CoQ10) in humans and a few other mammalian species because its side chain is comprised of 10 isoprene units. CoQ belongs to a homologous series of compounds that share a common benzoquinone ring structure but differ in the length of the isoprenoid side chain (Ernster and Dallner, 1995). ...
... In healthy individuals, normal serum/plasma CoQ10 concentrations usually range from 0.5 μg to 1.0 μg per mL and the total body pool of CoQ10 is estimated to be between 1.5 -2 gm in a healthy adult (Shults et al., 2004). Animal and human studies have demonstrated that approximately 2 to 10% of the dose administered is taken up into the blood (Zhang et al., 1995;Weber, 2001). ...
... It plays a central role in function and normal cell respiration therefore deficiency in CoQ10 availability or PDF created with pdfFactory Pro trial version www.pdffactory.com endogenous production disrupts normal cellular functions, and that may lead to abnormal patterns of cell division and may produce an oncogenic response (Ernster and Dallner, 1995;Crane, 2001). ...
This study was designed to assess the effect of different concentrations
of L-carnitine and Co enzyme Q10 (CoQ10) on the outcome of in vitro
human sperm activation and to find out if there are any side effects of Lcarnitine and CoQ10 on the sperm deoxyribonucleic acid (DNA) integrity
using DNA fragmentation index test. Eighty seven samples of semen of infertile and fertile men were randomly collected at the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies/Al- Nahrain University. The mean age of the men was (32.034 0.57) years with mean duration of infertility (4.644 0.25) years. Seminal fluid analyses were done involving macroscopic and microscopic examinations according to WHO criteria. Swim-up technique was dependent for in vitro sperm activation, the washed samples were divided before using centrifugation swim-up technique into 3 groups: control group
(G1) without L-carnitine and CoQ10. While, in G2 and G3 two
concentrations of L-carnitine (20μg, 40μg) and CoQ10 (20μg, 40μg) were
used respectively. Moreover, all groups within post-activation enriched with SMART- Pro media. The sperm parameters were evaluated after the addition of L-carnitine and CoQ10. Data were analyzed statistically using complete randomized design (CRD) (one way ANOVA).
Significant (P<0.05) differences were observed in the sperm parameters
of post-activation when compared with the pre-activation. In G2 and G3, at doses of ( 20μg and 40μg) of L-carnitine and CoQ10, the results showed a significant (P<0.05) increase in the percentages of sperm motility, progressive sperm motility and sperm morphology, in spite of the increase in the percentages of sperm motility, progressive sperm motility and sperm morphology was seen in G3 compared to G2. There were no significant (P>0.05) differences between G2 and G3. A significant (P<0.05) decrease in PDF created with pdfFactory Pro trial version www.pdffactory.com III fragmented sperm DNA percentage of post-activation was seen when compared with the pre-activation with non significant (P>0.05) differences between G2 and G3. Moreover, DNA fragmentation in the spermatozoa treated by 40μg L-carnitine and CoQ10 was the lowest among post-activation groups. From the results of this study, it can be concluded that the addition of 40 μg of L-carnitine and CoQ10 to washed sperms can improve sperm motility and sperm DNA integrity in vitro.
... Thus, the empirically derived regimen for oral administration of CoQ 10 takes advantage of its lipophilic solubility and recommends coadministration with lipid-rich foods (Zhou et al., 2014). Exogenous CoQ 10 is taken up from the intestine into chylomicrons and hence to the circulationsimilar to the uptake of a-tocopherolwith a range of between 2 and 4% of the total uptake (Zhang et al., 1995). In the plasma, CoQ 10 is mainly carried by lipoproteins, mostly in LDL particles where it is predominantly in its reduced form (Bhagavan et al., 2007;Zhang et al., 1995). ...
... Exogenous CoQ 10 is taken up from the intestine into chylomicrons and hence to the circulationsimilar to the uptake of a-tocopherolwith a range of between 2 and 4% of the total uptake (Zhang et al., 1995). In the plasma, CoQ 10 is mainly carried by lipoproteins, mostly in LDL particles where it is predominantly in its reduced form (Bhagavan et al., 2007;Zhang et al., 1995). The circulating concentrations of CoQ 10 may be useful for assessing its status in the body, and also for monitoring the response to CoQ 10 supplementation. ...
... Indeed, it is described that is threefold faster when CoQ 10 is administrated with food intake (Ochiai et al., 2007). CoQ 10 intestinal absorption follows the same process than lipids and it seems to be very limited (Zhang et al., 1995). ...
Coenzyme Q10 (CoQ10) is a ubiquitous molecule present in all eukaryotic organisms whose principal role in the cell is related to its participation in the electron transport chain in the inner mitochondrial membrane. CoQ10 plays a major role in the control of cell redox status, and both the amount and functionality of this molecule have been related to the regulation of reactive oxygen species generation. Numerous reports can be found discussing the implications of CoQ10 supplementation in human studies and clinical trials related to aging. However, few reviews have made an updating through the translational point of view to integrate both basic and clinical aspects. The aim of this paper is to review our current knowledge from CoQ10 implications at biochemical and physiological level, in order to unravel the molecular mechanisms involved in its application in clinical practice. Although the importance of CoQ10 has been mainly attributed to its role as an agent for energy transduction in mitochondria, new functions for CoQ10 have been described in the recent past years, including anti-inflammatory effects, gene expression regulation and lipid bilayer membranes stabilization, which explain its involvement in aging and age-related diseases such as cardiovascular diseases, renal failure and neurodegenerative diseases.
... CoQ is a molecule naturally found in different dietary sources, which can be taken up from intestinal lumen in a similar way to other lipids [83]. According to results from different studies in rats [96][97][98][99][100][101][102][103], it has been historically considered that approximately 6% of orally administered CoQ permeates the gastrointestinal tract into the blood and is transferred to liver and spleen. Consequently, uptake in the whole body ranged between 2% and 3% of the total dose. ...
... Consequently, uptake in the whole body ranged between 2% and 3% of the total dose. Moreover, CoQ 10 has been found in plasma, largely in the reduced form [100]. In vitro studies with CaCo-2 models of absorption have suggested that CoQ 10 is reduced to ubiquinol either during or following absorption [104]. ...
... In vitro studies with CaCo-2 models of absorption have suggested that CoQ 10 is reduced to ubiquinol either during or following absorption [104]. In turn, CoQ uptake by other tissues such as heart, kidney, brain and skeletal muscle was considered low or completely absent [100,102,103], unless endogenous levels fall below a critical threshold. ...
Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since then, more additional roles in cell physiology have been reported, including antioxidant, signaling, death prevention, and others. It is known that all cells are able to synthesize functionally sufficient amounts of CoQ under normal physiological conditions. However, CoQ is a molecule found in different dietary sources, which can be taken up and incorporated into biological membranes. It is known that mitochondria have a close relationship with the aging process. Additionally, delaying the aging process through diet has aroused the interest of scientists for many years. These observations have stimulated investigation of the anti-aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging. In this context, the present review focus on the current knowledge and evidence the roles of CoQ cells, its relationship with aging, and possible implications of dietary CoQ in relation to aging, lifespan or age-related diseases.
... Studies on animals have shown that the tissue uptake of CoQ 10 is limited in rats (19). In particular Zhang et al. (20) administrered 12 µmol CoQ 10 /100 g body weight by gastric intubation, daily up to 8 days. The amount of t-CoQ 10 rose significantly in the plasma and the liver, where it accumulated mainly in the lysosomes, but also in the other subcellular fractions prepared by differenzial centrifugation of the liver homogenate (20). ...
... In particular Zhang et al. (20) administrered 12 µmol CoQ 10 /100 g body weight by gastric intubation, daily up to 8 days. The amount of t-CoQ 10 rose significantly in the plasma and the liver, where it accumulated mainly in the lysosomes, but also in the other subcellular fractions prepared by differenzial centrifugation of the liver homogenate (20). In this study we have evaluated the plasma and tissue uptake of a prolonged (up to 60 days) dietary administration of CoQ 10 and ubiquinol diacetate (CoQ 10 DIA) in rats, having prevalently t-CoQ 9 as coenzyme Q, and in guinea pigs displaying exclusively t-CoQ 10 . ...
... After 60 days of treatment, guinea pig liver subfraction were prepared according to the scheme depicted in figure 2, as described by Zhang et al. (20). ...
In this study we have evaluated the uptake of a prolonged (up to 60 days) dietary administration of CoQ10 or ubiquinol diacetate (CoQ10 DIA) into the plasma and the tissues of rats having prevalently t-CoQ9 (CoQ9H2 + CoQ2) as coenzyme Q, and guinea pigs displaying exclusively t-CoQ10 (CoQ10H2 + CoQ10). In addition we have examined whether such administrations affected the plasma and the tissue levels of Vitamin E (Vit. E) and polyunsaturated fatty acids of phospholipid (PL-PUFA). Indipendently on the type of ubiquinone of the experimental animals (t-CoQ9 and/or t-CoQ10), the supplementation with CoQ10 led to a significant increase of t- CoQ10 in the plasma and in the liver of both rats and guinea pigs, but not in their heart, brain, pancreas, or kidney. In addition, the plasma and the tissue levels of membrane PL-PUFA and Vit. E, that works in sinergy with ubiquinol to protect PL-PUFA from oxidative injury, were not affected at all by the administration of ubiquinone. The results with CoQ10 DIA paralleled those with CoQ10 indicating that the diester, after its ingestion, is easily hydrolyzed to CoQ10H2 by esterase enzymes in the duodenum and small intestine and, under this form, absorbed, at the same way it occurs with α-tocopheryl acetate. In the guinea pig liver the increase of t-CoQ10 was mainly localized in the mitochondria and lysosomes.The plasma and the liver increases were transitory enough: in the guinea pigs the excess of t-CoQ10 taken up came back to normal levels of the controls within 3-5 days in the plasma and 6-8 days in the liver.
... Despite statin side effects being rarely severe, at times it is necessary to stop the therapy, exposing the patient to an increased cardiac risk [118]. With this in mind, the administration of ubiquinone complements was first proposed as a strategy to ameliorate statin side effects [121,122]. However, these complements were not demonstrated to satisfactorily reduce those major side effects, and ubiquinone was poorly orally absorbed [121,122]. ...
... With this in mind, the administration of ubiquinone complements was first proposed as a strategy to ameliorate statin side effects [121,122]. However, these complements were not demonstrated to satisfactorily reduce those major side effects, and ubiquinone was poorly orally absorbed [121,122]. Recently, commercial GGOH rich extracts and preparations were launched that have shown promising effects of restoring protein prenylation in this context [94,119,120]. In particular, GGOH supplements supported a beneficial effect against statin-induced myopathy and in the prevention of skeletal muscle fatigue in preliminary studies [119,120]. ...
Isoprenoids are the output of the polymerization of five-carbon, branched isoprenic chains derived from isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Isoprene units are consecutively condensed to form longer structures such as farnesyl and geranyl-geranyl pyrophosphate (FPP and GGPP, respectively), necessary for the biosynthesis of several metabolites. Polyprenyl transferases and synthases use polyprenyl pyrophosphates as their natural substrates; however, it is known that free polyprenols, such as farnesol (FOH), and geranylgeran-iol (GGOH) can be incorporated into prenylated proteins, ubiquinone, cholesterol, and dolichols. Furthermore, FOH and GGOH have been shown to block the effects of isoprenoid biosynthesis inhibitors such as fosmidomycin, bisphosphonates, or statins in several organisms. This phenomenon is the consequence of a short pathway, which was observed for the first time more than 25 years ago: the polyprenol salvage pathway, which works via the phosphorylation of FOH and GGOH. Biochemical studies in bacteria, animals, and plants suggest that this pathway can be carried out by two enzymes: a polyprenol kinase and a polyprenyl-phosphate kinase. However, to date, only a few genes have been unequivocally identified to encode these enzymes in photosynthetic organisms. Nevertheless, pieces of evidence for the importance of this pathway abound in studies related to infectious diseases, cancer, dyslipidemias, and nutrition, and to the mitigation of the secondary effects of several drugs. Furthermore, nowadays it is known that both FOH and GGOH can be incorporated via dietary sources that produce various biological effects. This review presents, in a simplified but comprehensive manner, the most important data on the FOH and GGOH salvage pathway, stressing its biomedical importance The main objective of this review is to bring to light the need to discover and characterize the kinases associated with the isoprenoid salvage pathway in animals and pathogens.
... The length of the polyisoprenoid tail varies between speciesthe human isoform consists mostly of 10 isoprene residues (CoQ10), whereas the rodent isoform has 9 (CoQ9) and yeast has 6 residues (CoQ6). CoQ is synthesized de novo in each cell, and based on biochemical studies performed in rats, it is estimated that only~2-4% of the dietary CoQ10 is taken up by the body [28]. In the same study, it was also shown that CoQ10 supplementation did not affect the endogenous CoQ9 biosynthesis [28]. ...
... CoQ is synthesized de novo in each cell, and based on biochemical studies performed in rats, it is estimated that only~2-4% of the dietary CoQ10 is taken up by the body [28]. In the same study, it was also shown that CoQ10 supplementation did not affect the endogenous CoQ9 biosynthesis [28]. While there may exist species-specific and formulation-specific differences in CoQ10 absorption, it is generally accepted that CoQ10 has low bioavailability in human tissue [29,30]. ...
Steroid-resistant nephrotic syndrome (SRNS) is a genetically heterogeneous kidney disease that is the second most frequent cause of kidney failure in the first 2 decades of life. Despite the identification of mutations in more than 39 genes as causing SRNS, and the localization of its pathogenesis to glomerular podocytes, the disease mechanisms of SRNS remain poorly understood and no universally safe and effective therapy exists to treat patients with this condition. Recently, genetic research has identified a subgroup of SRNS patients whose kidney pathology is caused by primary coenzyme Q10 (CoQ10) deficiency due to recessive mutations in genes that encode proteins in the CoQ10 biosynthesis pathway. Clinical and preclinical studies show that primary CoQ10 deficiency may be responsive to treatment with CoQ10 supplements bypassing the biosynthesis defects. Coenzyme Q10 is an essential component of the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. Studies in yeast and mammalian model systems have recently identified the molecular functions of the individual CoQ10 biosynthesis complex proteins, validated these findings, and provided an impetus for developing therapeutic compounds to replenish CoQ10 levels in the tissues/organs and thus prevent the destruction of tissues due to mitochondrial OXPHOS deficiencies. In this review, we will summarize the clinical findings of the kidney pathophysiology of primary CoQ10 deficiencies and discuss recent advances in the development of therapies to counter CoQ10 deficiency in tissues.
... Furthermore, a previous study of rats administered with CoQ10 supplement by gastric intubation found that CoQ10 was absorbed into the spleen, liver and serum. The uptake of CoQ10 by the liver tissue was found to be dose dependent, 10 µmol mg/100 g of body weight, whereas the uptake by the spleen could be to a large extent be accounted by the blood CoQ10 content of this organ [25]. CoQ9 is a major form of ubiquinone in the rat. ...
... In the control group, the rats fed with Pak-wanban leaves and CoQ10 supplementation, a reduced form was the major form of CoQ10 in the serum and liver tissues. The results agreed with Aberg et al. [28] and Zhang et al. [25] who found that a major portion of CoQ10 in serum and tissues was in a reduced form as the hydroquinone or ubiquinol with the exception of the brain and lungs. Data from rat studies indicate that CoQ10 is reduced to ubiquinol either during or following absorption in the intestine [26]. ...
Pak-wanban (Sauropus androgynus L. Merr.), a popular Thai vegetable, has been found to have a high content of Coenzyme Q10 (CoQ10), which is a powerful antioxidant. This study investigated the quantitation, absorption and tissue distribution of CoQ10 from raw and stir-fried Pak-wanban and its antioxidant activities in rats. Male Wistar rats (seven weeks old) were randomly grouped as follows: (1) control, (2) raw Pak-wanban powder of 0.5 mg CoQ10/kg/day, (3) stir-fried Pak-wanban powder of 0.5 mg CoQ10/kg/day, (4) stir-fried Pak-wanban powder of 1.0 mg CoQ10/kg/day, and (5) commercially CoQ10 supplement groups of 0.5 mg CoQ10/kg/day. The results found that stir-fried cooking did not significantly reduce the content of CoQ10 in the Pak-wanban leaves. After 3 weeks of experimentation, the level of CoQ10 in the plasma, liver and spleen was increased in all Pak-wanban groups when compared to the control group. The level of CoQ10 in the stir-fried Pak-wanban group was significantly higher than the raw Pak-wanban group but slightly lower than the CoQ10 supplement group. Liver alpha-tocopherol concentrations were markedly increased in rats that consumed a high dose of CoQ10 from stir-fried Pak-wanban of 1 mg of CoQ10/kg/day when compared with the control group. Plasma antioxidant activities (ORAC: FRAP: DPPH) were significantly increased in both groups of stir-fried Pak-wanban when compared with the control group. We concluded that CoQ10 in Pak-wanban could be well absorbed and improved the plasma antioxidant activities. Furthermore, cooking oil may increase the bioavailability of CoQ10 from vegetables. Therefore, it would be useful for vegetarian people.
... Neuroprotection via Ca 2 + buffering and antioxidant activity [35, UVB radiation damage Treatment of damaged skin [66,[80][81][82][83][84][85] Heart failure Supplementation required for improving patient condition [82,[86][87][88][89][90][91][92][93] Barth syndrome and membrane instability-related diseases CoQ 10 -based treatment for Barth syndrome patients Development of cholesterol-free liposome-based drug delivery systems [94][95][96][97][98][99][100][101][102][103][104][105][106] Insulin resistance Increase in insulin sensitivity by scavenging mitochondrial oxidants [107][108][109][110][111][112][113][114][115] Fibromyalgia Pain alleviation [116][117][118][119][120][121] Familial hypercholesterolemia and atherosclerosis Supplementation required for improving patient condition [122][123][124][125][126] Coenzyme Q 10 has been extensively used in the clinic due to its potent antioxidant properties. However, less known CoQ 10 properties have gained importance in the medical field in the past few years. ...
... For the reasons that have previously been discussed, CoQ 10 has received considerable attention as a supplement to treat patients suffering from diabetes. However, low oral bioavailability of CoQ 10 represents a substantial limitation, especially in situations of CoQ 10 deficiency, where mitochondrial homeostasis needs to be restored in metabolic tissues [111]. Therefore, a pharmaceutical alternative to supplementation would be to target cellular processes that play a part in the regulation of the mitochondrial CoQ 10 content. ...
The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
... However, oral CoQ 10 supplementation has been shown to elevate CoQ 10 skeletal muscle mitochondrial content in rodents and humans (Cooke et al., 2008;Kamzalov et al., 2003;Kon et al., 2007;Linnane et al., 2002). Although plasma CoQ 10 concentrations can easily be measured, this only reflects the bioavailability of CoQ 10 after oral supplementation, and not indicative of uptake into skeletal muscle (Duncan et al., 2005;Zhang et al., 1995). CoQ 10 has not been extensively researched in horses, although a few studies demonstrated oral CoQ 10 supplementation increases plasma concentrations (Sinatra et al., 2013a;Sinatra et al., 2013b). ...
... Most researchers now believe that the formulation of oral CoQ 10 (e.g. delivery system) is of equal, if not more, importance to the dosage, since this highly lipophilic molecule is typically poorly absorbed, resulting in a low bioavailability despite the oral dose used, as observed in humans, rats and dogs (Bank et al., 2011;Zhang et al., 1995;Zhang et al., 1996). ...
Coenzyme Q 10 (CoQ 10 ) is an essential component of the mitochondrial electron transport chain (ETC). Decreased skeletal muscle CoQ 10 content may result in decreased ETC activity and energy production. This study tested the hypotheses that supplementation with oral CoQ 10 will increase plasma CoQ 10 concentrations and that prolonged supplementation will increase skeletal muscle CoQ 10 content in young, healthy untrained Thoroughbreds. Nineteen Thoroughbreds (27.5±9.7 months old; 11 males, eight females) from one farm and maintained on a grass pasture with one grain meal per day were supplemented daily with 1.5 mg/kg body weight of an oral CoQ 10 -β-cyclodextrin inclusion complex. Whole-blood and skeletal muscle biopsies were collected before (T 0 ) and after (T 1 ) nine weeks of supplementation. Plasma CoQ 10 concentrations were determined via high-performance liquid chromatography. Skeletal muscle mitochondrial ETC combined complex I+III enzyme activity (indirect measurement of CoQ 10 content) was assessed spectrophotometrically and normalised to mitochondrial abundance. Horses accepted supplementation with no adverse effects. Plasma CoQ 10 concentration increased in all horses following supplementation, with mean plasma CoQ 10 concentration significantly increasing from T 0 to T 1 (0.13±0.02 vs 0.25±0.03 μg/ml; mean difference 0.12±0.03; P=0.004). However, variability in absorbance resulted in a 58% response rate (i.e. doubling of T 1 above T 0 values). The mean skeletal muscle complex I+III activity significantly increased from T 0 to T 1 (0.36±0.04 vs 0.59±0.05 pmol/min/mg of muscle, mean difference 0.23±0.05; P=0.0004), although T 1 values for three out of 19 horses decreased on average by 23% below T 0 values. In conclusion, oral supplementation with CoQ 10 in the diet of young, healthy untrained Thoroughbreds increased mean plasma CoQ 10 concentration by 99% with prolonged daily supplementation increasing mean skeletal muscle complex I+III activity by 65%. Additional research is warranted investigating training and exercise effects on skeletal muscle CoQ 10 content in CoQ 10 supplemented and un-supplemented Thoroughbreds.
... Thus, absorption of CoQ is enhanced in the presence of lipids. Following absorption, CoQ is incorporated into chylomicrons and is transported to the systemic circulation via the lymphatic system [100]. In plasma, CoQ is mainly carried by lipoproteins, mostly in LDL particles where it is predominantly found in its reduced form [100,101]. ...
... Following absorption, CoQ is incorporated into chylomicrons and is transported to the systemic circulation via the lymphatic system [100]. In plasma, CoQ is mainly carried by lipoproteins, mostly in LDL particles where it is predominantly found in its reduced form [100,101]. Determination of CoQ levels in the blood may be useful for assessing its content in the body and treatment adherence. ...
Atherosclerosis is the most common cause of cardiac deaths worldwide. Classically, atherosclerosis has been explained as a simple arterial lipid deposition with concomitant loss of vascular elasticity. Eventually, this condition can lead to consequent blood flow reduction through the affected vessel. However, numerous studies have demonstrated that more factors than lipid accumulation are involved in arterial damage at the cellular level such as inflammation, autophagy impairment, mitochondrial dysfunction, and/or free radical overproduction. In order to consider the correction of all of these pathological changes, new approaches in atherosclerosis treatment are necessary. Ubiquinone or coenzyme Q10 is a multifunctional molecule that could theoretically revert most of the cellular alterations found in atherosclerosis such as cholesterol biosynthesis dysregulation, impaired autophagy flux and mitochondrial dysfunction thanks to its redox and signaling properties. In this review, we will show the latest advances in the knowledge of the relationships between coenzyme Q10 and atherosclerosis. In addition, as atherosclerosis phenotype is closely related to aging, it is reasonable to believe that coenzyme Q10 supplementation could be beneficial for both conditions.
... En un estudio con ratas a las que se les administró oralmente coenzima Q10, se observó que ésta aparece en la circulación, hígado y bazo más no en el corazón o riñón, además, que la Q10 encontrada en el hígado resultó ser dosis dependiente sobre los 12mmol/100gr de peso corporal (Zhang Y, 1995). ...
... de la síntesis de novo(Zhang Y, 1995). Por lo que, el incremento de la concentración de esta coenzima en el plasma, puede incluso enmascarar la deficiencia de la misma en el tejido, siendo este lugar el que posee la concentración de interés, ya que es donde se produce una significativa disminución en pacientes con enfermedades mitocondriales, cardíacas y musculares.(Ghirlanda ...
The coenzyme Q10 is a fat soluble antioxidant essential for optimal functioning of all cell types. Currently, it is recommended for use as an adjunct in the treatment of mitochondrial, hypertensive and heart diseases, so, is necessary to establish analytical methods to objectively measure concentrations of this coenzyme in tissue of medical interest.
The objective of this thesis was to standardize and validate a measurement protocol of Coenzyme Q10 in platelets by the method of HPLC (high performance liquid chromatography), so, several tests such as composition mobile phase variation, flow rate variation, sample injection volume variation, among others, were realizated to optimize parameters of method. And other tests of: accuracy, precision, robustness, linearity, sensitivity, identity and uncertainty, to determine quality parameters of method.
The results of the validation of this method were satisfactory, and met international standards recognized at regulation of analytical methods such as those given by the Eurachem, ICH and USP.
... Under normal physiological conditions, endogenous CoQ 9 in rat liver tissue is predominantly located in the mitochondrial subcellular fraction [183]. After CoQ 10 supplementation, subcellular fractionation of hepatic tissue cells was investigated [191]. The pellet containing lysosomes and light mitochondria was especially enriched in CoQ 10 , with no change to the endogenous levels of CoQ 9 . ...
Coenzyme Q (CoQ) is an essential lipid with many cellular functions, such as electron transport for cellular respiration, antioxidant protection, redox homeostasis, and ferroptosis suppression. Deficiencies in CoQ due to aging, genetic disease, or medication can be ameliorated by high-dose supplementation. As such, an understanding of the uptake and transport of CoQ may inform methods of clinical use and identify how to better treat deficiency. Here, we review what is known about the cellular uptake and intracellular distribution of CoQ from yeast, mammalian cell culture, and rodent models, as well as its absorption at the organism level. We discuss the use of these model organisms to probe the mechanisms of uptake and distribution. The literature indicates that CoQ uptake and distribution are multifaceted processes likely to have redundancies in its transport, utilizing the endomembrane system and newly identified proteins that function as lipid transporters. Impairment of the trafficking of either endogenous or exogenous CoQ exerts profound effects on metabolism and stress response. This review also highlights significant gaps in our knowledge of how CoQ is distributed within the cell and suggests future directions of research to better understand this process.
... Moreover, CoQ in general shows limited gastrointestinal absorption and bioavailability due to its chemical-physical properties [17]. Dietary CoQ 10 distribution shows tissue specific differences in uptakewith plasma showing the most increases and muscle tissue showing the least [18,19]. This represents a unique feature of CoQ 10 that behaves differently from similar lipophilic molecules such as tocopherol that seem to be less tissue specific [20]. ...
Coenzyme Q10 (CoQ10) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ10 uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ10 content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ10 following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ10 for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ10 crystalline form. After supplementation, plasma was collected for CoQ10 determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ10 content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ10-enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ10 to skin and muscle tissues.
... However, its therapeutic applications are greatly limited because CoQ 10 is almost insoluble in water (due to its high hydrophobicity) and has relatively large molecular mass (863.34 g/mol). In rats, only about 2-4 % of orally administered CoQ 10 could be absorbed (Zhang et al. 1995). Divided dosages (2 x100 mg) produce a larger increase in plasma levels than a single peroral 200 mg dose (Singh et al. 2005). ...
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).
... Lipoproteins-mainly LDL particles-carry the bulk of coenzyme Q10 in plasma, which is primarily in its reduced form. CoQ10 levels in the blood can be used to assess CoQ10 concentration in the body and treatment compliance (Zhang et al., 1995). ...
This review paper aims to examine recent Randomized Clinical Trials (RCTs) and review articles evaluating the role of CoQ10 in the management of atherosclerosis, and coronary heart disease, with particular focus on Statin-Associated Muscle Symptoms (SAMS), chronic heart failure, and the effect on cardiovascular risk factor s. With an evaluation of its impacts on patients' well-being, it seeks to outline the existing opportunities for using CoQ10 in a multitude of cardiovascular, neurodegenerative, and metabolic disorders.
... Secondary deficiency of CoQ10 are well documented in ageing [46,47] and increased request due to intense physical exercise [48] or disease conditions associated with increased oxidative stress [49]. Nutritional supplementation might represent a useful strategy in the latter conditions however CoQ10 is characterized by a very low bioavailability with low levels of dietary CoQ10 being absorbed and as much as 95% being eliminated with feces [50]. Notably, beside general absorption issues in the digestive tract, selective absorption by different tissues and intracellular translocation remain poorly understood. ...
Myalgia and new-onset of type 2 diabetes have been associated with statin treatment, which both could be linked to reduces coenzyme Q10 (CoQ10) in skeletal muscle and impaired mitochondrial function. Supplementation with CoQ10 focusing on levels of CoQ10 in skeletal muscle and mitochondrial function has not been investigated in patients treated with statins. To investigate whether concomitant administration of CoQ10 with statins increases the muscle CoQ10 levels and improves the mitochondrial function, and if changes in muscle CoQ10 levels correlate with changes in the intensity of myalgia. 37 men and women in simvastatin therapy with and without myalgia were randomized to receive 400 mg CoQ10 daily or matched placebo tablets for eight weeks. Muscle CoQ10 levels, mitochondrial respiratory capacity, mitochondrial content (using citrate synthase activity as a biomarker), and production of reactive oxygen species were measured before and after CoQ10 supplementation, and intensity of myalgia was determined using the 10 cm visual analogue scale. Muscle CoQ10 content and mitochondrial function were unaltered by CoQ10 supplementation. Individual changes in muscle CoQ10 levels were not correlated with changes in intensity of myalgia. CoQ10 supplementation had no effect on muscle CoQ10 levels or mitochondrial function and did not affect symptoms of myalgia.
... The second limitation is the use of serum blood samples for biochemical analysis in order to demonstrate the long-term effect while tissue sample analysis could have served our purpose better. Third, only about 2-3% of orally-administered CoQ10 has been reported to be absorbed 44 . Therefore, studies are needed to evaluate the most effective daily dose and duration of use or the outcome of IV CoQ10 administration. ...
Purpose:
To evaluate the therapeutic effects of methylprednisolone, the CoenzymeQ10 (CoQ10) structural analogue idebenone, and both together on the optic nerve (ON) and retinal layers following methanol intoxication in rats with histopathological and biochemical methods.
Materials and methods:
This experimental study was conducted with 30 male Wistar rats. The rats were divided into five equal groups depending on the treatment protocol:healthy controls (HC), methanol (M), methanol + methylprednisolone (MM), methanol + idebenone (MI), and methanol + methylprednisolone + idebenone (MMI).Distilled water was provided orally to the HC group, while 20% methanol was administered orally at a dose of 3 g/kg with a nasogastric tube to all rats in groups except the HC group. Four hours later, group MM received 1 mg/kg of intraperitoneal methylprednisolone for 10 days using an insulin syringe, and group MI received 20 mg/kg idebenone by nasogastric catheter for 28 days. MMI group was administered oral idebenone and intraperitoneal methylprednisolone at the same dose. Serum samples were obtained on the 28th day for biochemical analysis and afterwards the rats were euthanized for histopathological examination and eyes were enucleated. ON was evaluated for circumference thickness, vascularization and number of astrocytes, also retinal layers were examined for structural changes by histopathological examination.
Results:
Comparison of the antioxidant and oxidative stress biomarkers between the groups revealed no statistically significant difference (p > 0.05). By histopathological evaluation the most marked results were obtained by MMI group with an improvement of all parameters mentioned. There was no statistically significant difference between MM group and M group for RD score (p = 0.123). In addition, ON vacuolization in MI group (p < 0.001) and ON astrocyte increase in both MI and MMI groups were statistically significantly lower than in M group (p = 0.001, p = 0.001, respectively).
Conclusions:
The early use (within hours) of idebenone and short-term methylprednisolone treatment together may protect against the retinal and ON damage developing after methanol ingestion in rats as guided by the histopathological data.
... Chemically, CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is syn-thesized endogenously in the body from tyrosine (benzoquinone ring) and mevalonic acid (isoprenoid side chain) [8]. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP) [9]. As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. ...
Introduction:
Diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) have become some of the most urgent and prevalent health problems in recent decades, side by side with the growing obesity crisis. The intimate relationship between T2DM and CVD has become clear: endothelial dysfunction caused by oxidative stress and inflammation resulting from hyperglycaemia is the key factor in the development of vascular complications of T2DM, leading to CVD. Coenzyme Q10 (CoQ10) is a great candidate for the treatment of these diseases, acting precisely at the intersection between T2DM and CVD: oxidative stress, due to its strong antioxidant activity and fundamental physiological role in mitochondrial bioenergetics. CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is synthesized endogenously in the body from tyrosine and mevalonic acid. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP). As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 supplementation has been used as an intensifier of mitochondrial function and an antioxidant with the aim of palliating or reducing oxidative damage that can worsen the physiological outcome of a wide range of diseases including T2DM and CVDs.
Conclusion:
Although there is not enough evidence to conclude it is effective for different therapeutic indications, CoQ10 supplementation is probably safe and well tolerated, with few drug interactions and minor side effects. Many valuable advances have been made on the use of CoQ10 in clinical practice for patients with T2DM and a high risk of CVD. However, further research is needed to assess the real safety and benefit to indicate CoQ10 supplementation in patients with T2DM.
... First, because of its relatively high molecular weight (863.34 g/mol) and insolubility in water, poor oral bioavailability has been a limitation for CoQ 10 supplementation, which may become more evident in large MI complicated by peripheral hypoperfusion (23,103). In rats, only a small part of orally supplemented CoQ 10 was found to reach the circulation, spleen, and liver with none reached the heart or kidney (104,105). However, CoQ 10 as a lipid microsphere given intravenously reached both the heart and kidney as well as other tissues in rats (104,106). ...
Objective
Effective interventions that might limit myocardial ischemia-reperfusion (I/R) injury are still lacking. Coenzyme Q 10 (CoQ 10 ) may exert cardioprotective actions that reduce myocardial I/R injury. We conducted this meta-analysis to assess the potential cardioprotective effect of CoQ 10 in animal models of myocardial I/R injury.
Methods
We searched PubMed and Embase databases from inception to February 2022 to identify animal studies that compared the effect of CoQ 10 with vehicle treatment or no treatment on myocardial infarct size in models of myocardial I/R injury. Means and standard deviations of the infarct size measurements were pooled as the weighted mean difference with 95% confidence interval (CI) using the random-effects model. Subgroup analyses were also conducted according to animals' species, models' type, and reperfusion time.
Results
Six animal studies (4 in vivo and 2 ex vivo ) with 116 animals were included. Pooled analysis suggested that CoQ 10 significantly reduced myocardial infarct size by −11.36% (95% CI: −16.82, −5.90, p < 0.0001, I ² = 94%) compared with the control group. The significance of the pooled effect estimate was maintained in rats, Hartley guinea pigs, and Yorkshire pigs. However, it became insignificant in the subgroup of rabbits −5.29% (95% CI: −27.83, 17.26; I ² = 87%). Furthermore, CoQ 10 significantly reduced the myocardial infarct size regardless of model type (either in vivo or ex vivo ) and reperfusion time (either ≤ 4 h or >4 h).
Conclusion
Coenzyme Q 10 significantly decreased myocardial infarct size by 11.36% compared with the control group in animal models of myocardial I/R injury. This beneficial action was retained regardless of model type and reperfusion time.
... However, its therapeutic applications are greatly limited because CoQ10 is almost insoluble in water (due to its high hydrophobicity) and has relatively large molecular mass (863.34 g/mol). In rats, only about 2-4 % of orally administered CoQ10 could be absorbed (Zhang et al. 1995). Divided dosages (2 x100 mg) produce a larger increase in plasma levels than a single peroral 200 mg dose (Singh et al. 2005). ...
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).
... CoQ10 is a higher molecular weight (863.34 g/mol) highly lipophilic compounds which come under Biopharmaceutical Classification System (BCS) class II [5] (fig. 1), practically insoluble in water [6] , dietary absorption of Q10 is very mild and confined [7] . CoQ10 has an outstanding safety profile, as proved by a large number of preclinical and clinical studies, in both adults and children [8][9][10] . ...
... Human blood vessels and microcirculation systems transform with rising BP. These changes are particularly clear for patients with serious hypertension (Zhang et al, 1995). In various stages, hypertension can prompt fluctuating levels of cardiovascular dispersal change; some changes are brief or reversible (unstable changes, for example, prehypertension or stage 1 hypertension), while others are irreversible (fatal changes, for example, stage 2 hypertension and serious hypertension, for which it is hard to restore the standard BP level). ...
This study has assessed the effect of coenzyme Q10 among patients with systolic and diastolic blood pressure of prehypertensive of 50 participants including 30 males and 20 females were selected for this research according to their clinical diagnosis of prehypertensive symptoms, the study was placed in were seen in Al-Sader Teaching Hospital, in Misan hospital, IRAQ. The patients were divided by half into the control group and the other group which received the Q10 within their diet and lifestyle for 12 weeks. The results showed that the daily consumption of coenzyme q10 (200mg) with significant improvements in both systolic and diastolic blood pressure in prehypertensive patients.
... Furthermore, CoQ10 can be derived from the diet (about 5 mg/day for a Mediterranean diet). In particular it is present in fatty fishes, soja, nuts, and spinach [11], however, its intake may not be sufficient to counteract physiological or pathological deficiencies [12]. For this reason, nutritional supplementation with this nutraceutical could help to maintain adequate levels within the body. ...
Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients’ health and quality of life.
... On the other hand, CoQ 10 can be derived from the diet; in particular, fatty fish (salmon, sardin, and tuna), soya, spinach, and nuts contain high levels of this cofactor. However, the intake from the diet is significant only in deficiency conditions [14]. Some factors may reduce plasma concentrations of CoQ 10 , such as aging, genetic factors, drugs (e.g., statins), certain diseases (e.g., cardiovascular disease and degenerative muscle disorders), and increased demand [15]. ...
Coenzyme Q10 (CoQ10) is a ubiquitous factor present in cell membranes and mitochondria, both in its reduced (ubiquinol) and oxidized (ubiquinone) forms. Its levels are high in organs with high metabolism such as the heart, kidneys, and liver because it acts as an energy transfer molecule but could be reduced by aging, genetic factors, drugs (e.g., statins), cardiovascular (CV) diseases, degenerative muscle disorders, and neurodegenerative diseases. As CoQ10 is endowed with significant antioxidant and anti-inflammatory features, useful to prevent free radical-induced damage and inflammatory signaling pathway activation, its depletion results in exacerbation of inflammatory processes. Therefore, exogenous CoQ10 supplementation might be useful as an adjuvant in the treatment of cardiovascular diseases such as heart failure, atrial fibrillation, and myocardial infarction and in associated risk factors such as hypertension, insulin resistance, dyslipidemias, and obesity. This review aims to summarize the current evidences on the use of CoQ10 supplementation as a therapeutic approach in cardiovascular diseases through the analysis of its clinical impact on patients’ health and quality of life. A substantial reduction of inflammatory and oxidative stress markers has been observed in several randomized clinical trials (RCTs) focused on several of the abovementioned diseases, even if more RCTs, involving a larger number of patients, will be necessary to strengthen these interesting findings.
... The levels of ROS, NO, H 2 O 2 , NADPH oxidase, TBARS, carbonylated proteins, GSH, GSSG, SOD, CAT, GPx, GR, and GST in the renal tissue homogenates were measured following the established protocols mentioned earlier. Co-enzymes Q9 and Q10 in the cell lysate were separated and quantified using reverse phase-high performance liquid chromatographic (RP-HPLC) (Dionex, Germany) methods as described by Zhang and co-workers [34]. DNA fragmentation in the renal cells was measured using the diphenylamine reagent [11]. ...
Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl2 (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling pathways, respectively. In contrast, CA treatment significantly attenuated Cd-provoked nephrotoxicity via inhibiting free radicals, endorsing redox defence, suppressing apoptosis, and inhibiting fibrosis in renal cells in both in vitro and in vivo systems. In addition, CA treatment significantly (p < 0.05–0.01) restored blood and urine parameters to near-normal levels in mice. Histological findings further confirmed the protective role of CA against Cd-mediated nephrotoxicity. Molecular docking predicted possible interactions between CA and Nrf2/TGF-β1/Smad/collagen IV. Hence, CA was found to be a potential therapeutic agent to treat Cd-mediated nephrotoxicity.
... In animal studies, CoQ 10 intake appeared to increase in antioxidative potential of tissues [10]. However, several studies insisted that the endogenous production level was enough to provide sufficient CoQ 10 to prevent deficiency in young healthy animals [11,12]. ...
A total of 24 SD rats were allotted to four treatment groups such as the control (CON), 1% of cholesterol diet (CHO), 0.5% of coenzyme Q10 (COQ) and 1% of cholesterol plus 0.5% of coenzyme Q10 (CHCQ) groups to determine the effects of coenzyme Q10 (CoQ10) on the antioxidant defense system in rats. The body weight, weight gain, liver weight and abdominal fat pads were unaffected by 0.5% of CoQ10 supplement in the rats. The level of triglyceride and HDL-cholesterol levels in the blood was significantly increased (p < 0.05) by the 1% of cholesterol supplement (CHO), whereas 0.5% of CoQ10 supplement (COQ) did not alter these blood lipid indices. In the mRNA expression, there was a significant effect (P < 0.05) of the CoQ10 supplement on the mRNA expression of superoxide dismutase (SOD), although the mRNA expression of glutathione peroxidase (GPX) and glutathione S-transferase (GST) was unaffected by cholesterol or the CoQ10 supplement. Similar to mRNA expression of SOD, its activity was also significantly increased (P < 0.05) by CoQ10, but not by the cholesterol supplement effect. The activities hepatic GPX and GST were unaffected by CoQ10 and cholesterol supplements in rats. Lipid peroxidation in the CHO group resulted in a significant (p < 0.05) increase compared with that in the other groups, indicating that the CoQ10 supplement to 1% of cholesterol-fed rats alleviated the production of lipid peroxidation in the liver. In conclusion, 0.5% of the CoQ10 supplement resulted in positive effects on the hepatic antioxidant defense system without affecting blood lipid indices in 1% of cholesterol fed rats.
... La coenzima Q10 se determina frecuentemente en plasma o suero sanguíneo, sin embargo existen algunos estudios que cuestionan el valor de estas mediciones, puesto que no reflejarían exactamente la concentración intracelular de la misma (Zhang Y, 1995) (Niklowitz, 2004) y por lo tanto su relación con patologías tales como Isquemia miocárdica, hipertensión, Alzheimer, Huntington, entre otras (Beal, 1999) (Munkholm, 1999) (Langsjoen, 1999), podría ser discutida. Es por ello que recientemente para la investigación clínica del rol de la CoQ10 en las patologías antes mencionadas, se está poniendo atención a su determinación en células sanguíneas, siendo las células predilectas las plaquetas, debido a que son ricas en mitocondrias, se pueden aislar fácilmente de pequeños volúmenes de sangre y presentan varias semejanzas con las neuronas, lo que posibilita el estudio de los mecanismos metabólicos y bioquímicos de varios desórdenes de tipo neurológico (Contin, 2011) (Bhagavan, 2006). ...
... The protein carbonylation was determined in accordance with the standard protocol [59]. The levels of co-enzymes Q9 and Q10 within the cell lysate were separated and quantified by RP-HPLC (Dionex, Germany) analyses as described earlier by Zhang and co-workers [60]. The levels of the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR) were measured following methods described elsewhere [61]. ...
The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.
... Nephrotic syndrome (NS), either in isolation or as part of an infantile multi-systemic disease, is the most common manifestation associated with CoQ 10 deficiency due to mutations in genes encoding for proteins involved in CoQ 10 biosynthesis (primary CoQ 10 deficiency), and is the most responsive to CoQ 10 supplementation [1]. However, the mechanism of the selective responsiveness of NS is not clear, because, paradoxically, kidney is one of the organs with the poorest uptake of exogenous CoQ 10 [2,3]. ...
Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q10 (CoQ10) deficiency and is very responsive to CoQ10 supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ10 supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ10 supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ10 antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.
... Our study provides a reasonable rationale for targeting the CoQ biosynthesis pathway as a potential therapeutic target. Overall low bioavailability of orally administered CoQ 10 or CoQ 10 H 2 represents a substantial limitation, particularly in situations of modest CoQ deficiency such as those shown here to be sufficient to initiate insulin resistance, and where mitochondrial CoQ homeostasis needs to be restored in metabolic tissues such as adipose and muscle (Zhang et al., 1995). We overcame this limitation in mice by intra-peritoneal administration of CoQ to provide proof-of-principle that restoration of mitochondrial CoQ improves insulin action and whole body glucose tolerance (Figure 4). ...
Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.
... Even though the absorption levels of CoQ 10 are increased in the presence of lipids, temporarily boosting the blood concentration, no overall uptake into tissues could be observed. 11) Due to the hydrophobic nature of CoQ 10 , the use of a liposomal carrier for the delivery might be possible. Since CoQ 10 is largely located in the inner mitochondrial membrane, a mitochondrial-targeted delivery system will be needed. ...
While Coenzyme Q10 (CoQ10) is thought to be effective for the treatment of a variety of diseases, it limits its cellular uptake. Because of the hydrophobic nature of CoQ10, it is reasonable to assume that it could be encapsulated within a liposomal carrier. Several reports regarding the packaging of CoQ10 in liposomes have appeared, but detailed investigations of the preparation of CoQ10 encapsulated liposomes have not been reported. As a result, information regarding the optimal method of packaging CoQ10 in liposomes is not available. In this study, several types of liposomes were prepared using different methods and their characteristics were compared. Since CoQ10 is mainly located in the inner mitochondrial membrane, a liposome that targets mitochondria, a MITO-Porter, was used as a model liposome. It was possible to incorporate high levels of CoQ10 into the carrier. Transmission electron microscopy analyses showed that an empty MITO-Porter and the CoQ10-MITO-Porter were structurally different from one another. Even though significant structural differences were observed, mitochondrial delivery was not affected in mitochondrial disease fibroblast cells, as evidenced by confocal laser scanning microscopy observations. The results reported herein suggest that the CoQ10-MITO-Porter might be a suitable candidate for the potential medical therapy of mitochondria-related diseases.
Graphical Abstract Fullsize Image
... The carbonylation of proteins was measured as per the method described by Uchida and Stadtman (1993). Co-enzymes Q 9 and Q 10 were appraised employing RP-HPLC as per standard protocol (Zhang et al., 1995). The level of reduced glutathione (GSH) was assayed by the method described by Hissin and Hilf (1973). ...
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera of T2D rats revealed the occurrence of hyperlipidemia and diabetic pathophysiology. A significantly (p < 0.01) high levels of serum C-reactive protein and pro-inflammatory mediators revealed the establishment of inflammatory occurrence in T2D rats. Besides, significantly high levels of troponins in the sera revealed the establishment of cardiac dysfunctions in T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly reverse the changes in serum biochemical parameters related to cardiac dysfunctions. Molecular mechanism studies demonstrated impairment of signaling cascade, IRS1/PI3K/Akt/AMPK/p 38/GLUT4, in glucose metabolism in the skeletal muscle of T2D rats. Significant (p < 0.01) activation of polyol pathway, enhanced production of AGEs, oxidative stress and up-regulation of inflammatory signaling cascades (PKC/NF-κB/PARP) were observed in the myocardial tissue of T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly (p < 0.05–0.01) stimulate glucose metabolism in skeletal muscle, regulated glycemic and lipid status, reduced the secretion of pro-inflammatory cytokines, and restored the myocardial physiology in T2D rats near to normalcy. Histological assessments were also in agreement with the above findings. In silico molecular docking study again supported the interactions of protocatechuic acid with Frontiers in Pharmacology | www.frontiersin.org 1 May 2017 | Volume 8 | Article 251 Bhattacharjee et al. Protocatechuic Acid Suppresses Diabetic Cardiomyopathy different signaling molecules, PI3K, IRS, Akt, AMPK PKC, NF-κB and PARP, involved in glucose utilization and inflammatory pathophysiology. In silico ADME study predicted that protocatechuic acid would support the drug-likeness character. Combining all, results would suggest a possibility of protocatechuic acid to be a new therapeutic agent for DC in future.
... Assessment of antioxidant markers related to organ dysfunction The intercellular ROS, TBARS level, protein carbonylation, antioxidant enzymes, non-enzymatic antioxidant were assayed following standard assay protocols as mentioned above. The levels of Co-enzymes Q 9 and Q 10 within the tissue extract were measured by the method as described earlier (Zhang et al., 1995). ...
Ipomoea aquatica Forssk. (Convolvulaceae) is an aquatic vegetable traditionally employed against toxic effects of xenobiotics. The present study has been designed to investigate the molecular mechanism underlying the beneficial role of the edible (aqueous) leaf extract of I. aquatica (AEIA) against doxorubicin (Dox)-induced liver injury. AEIA exhibited a dose-dependent (∼400 μg/ml) increase in cell viability against Dox (1 μM) in isolated rodent hepatocytes. AEIA (400 μg/ml) prevented the Dox-induced increase in ROS, redox imbalance, and activation of mitogen activated protein kinases (MAPK) and intrinsic pathway of apoptosis in hepatocytes. In the in vivo assay, administration of AEIA (100 mg/kg, p.o.) against Dox (3 mg/kg, i.p.) also reduced the oxidative impairment, DNA fragmentation, ATP formation, and up-regulated the mitochondrial co-enzymes Qs in the liver tissues of Wister rats. Histological assessments were in agreement with the biochemical findings. Substantial quantities of phyto-antioxidants in AEIA may mediate itsbeneficial function against Dox-induced liver injury.
... Coenzyme Q, also known as ubiquinone, is a hydrophobic lipophilic molecule synthesized by all animal tissues. It is an important component of the mitochondrial electron transport system and its reduced form (ubiquinol) works as an antioxidant [1]. The major coenzyme Q in higher plants and mammals is coenzyme Q10 (CoQ10), which contains 10 isoprenoid units [2]. ...
Objective:
To examine the effects of Rhaodobacter sphaeroides supplementation as a direct-fed microbial (DFM) on rumen fermentation in dairy cows and on CoQ10 transition into milk, an in vitro rumen simulation batch culture and an in vivo dairy cow experiments were conducted.
Methods:
The characteristics of in vitro ruminal fermentation were investigated using rumen fluids from six cannulated Holstein dairy cows at 2 h post-afternoon feeding. A control treatment was included in the experiments based on a typified total mixed ration (TMR) for lactating dairy cows, which was identical to the one used in the in vivo study, plus R. sphaeroides at 0.1, 0.3, and 0.5% TMR dry matter. The in vivo study employed six ruminally cannulated Holstein lactating cows randomly allotted to either the control TMR (C-TMR) treatment or to a diet supplemented with a 0.5% R. sphaeroides culture (S-TMR, dry matter basis) ad libitum. The presence of R. sphaeroides was verified using denaturing gradient gel electrophoresis (DGGE) applied to the bacterial samples obtained from the in vivo study. The concentration of CoQ10 in milk and in the supernatant from the in vitro study was determined using high performance liquid chromatography.
Results:
The results of the in vitro batch culture and DGGE showed that the concentration of CoQ10 significantly increased after 2 h of R. sphaeroides supplementation above 0.1%. When supplemented to the diet of lactating cows at the level of 0.5%, R. sphaeroides did not present any adverse effect on dry matter intake and milk yield. However, the concentration of CoQ10 in milk dramatically increased, with treated cows producing 70.9% more CoQ10 than control cows.
Conclusion:
The CoQ10 concentration in milk increased via the use of a novel DFM, and R. sphaeroides might be used for producing value-added milk and dairy products in the future.
... CoQ10 is a lipophilic, high molecular weight, antioxidant molecule which plays an essential role in the mitochondrial electron transport chain; its depletion is described as potentially leading to neu- romuscular and/or neurodegenerative disorders (16) and fibromyalgia (17). CoQ10, because of its chemical and physical features, is characterised by low oral bioavailability, which was re- ported in the rat to be only about 2-3% of the orally administered coenzyme (18). In the case of supplementation with finished dosage forms of CoQ10, absorption is likely also dependent on the chemical characteristics of the for- mulation, with water-soluble CoQ10 in particular shown to have enhanced bioavailability compared to oily and powder forms (19)(20)(21). ...
Decreased antioxidant capacity and increased oxidative stress have been observed in fibromyalgia patients. Some trials have also shown that CoQ10 levels are reduced in these patients but that supplementation can restore levels and reduce fibromyalgia symptoms, including pain and fatigue. We evaluated the effect of administration of a finished form of CoQ10 (DDM Chinone®) at a dose of 200 mg×2/day in 22 female subjects with a diagnosis of fibromyalgia in a randomized, open-label, cross-over study. Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue (by ~22%) and sleep disturbance (by ~33%). These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia.
... Supplementation of CoQ10 for a period of 29 days showed reduction in EOF% but thereafter fragility increased which credited as an age related effect in broilers 2 . However, the increased fragility at 40 mg/kg might be due to auto-oxidation of CoQ10 which would have resulted in mitochondrial ROS production or might be due to the influence of age of the birds on the absorption of CoQ10 30,31 . Hence, CoQ10 at 20 mg/kg could be considered as an option for the treatment for ascites mortality 32 . ...
In poultry, coenzyme Q10 (CoQ10) is widely used as a feed additive to control mortality due to ascites in broilers. Apart from its use the treatment of a variety of disorders viz., ischemic heart disease, diabetes mellitus, Parkinson's disease, muscle fatigue and muscle weakness, its supplementation has been reported to be beneficial for cardiovascular disease, chronic heart failure, cancer, migraine, asthma and hypertension. In this study, we investigated the effect of CoQ10 supplementation on serum protein, serum minerals, blood parameters, ascites susceptibility and humoral immune status in broilers fed with different energy levels which influence their productivity, biochemical profile and ascites incidences. The treatment had three levels of CoQ10, namely 0, 20 and 40 mg/kg at normal (NE), low (LE) and high (HE) energy levels in which 2X3 factorial design was followed. The haemoglobin and packed cell volume were not affected (P >0.05) by either energy or CoQ10 levels but the erythrocyte osmotic fragility per cent (EOF %) and blood glucose levels were decreased by CoQ10 supplementation at both 20 and 40 mg/kg. The serum calcium level had significantly (P <0.01) increased with CoQ10 at 40 mg/kg (12.70 vs. 11.58 and 11.98 mg/dL) in NE diet group over the unsupplemented and 20 mg/kg supplemented birds. Compared to the respective unsupplemented groups, CoQ10 @40 mg/kg reduced (P <0.01) the serum total protein (4.69 vs. 5.23 g/dL) and serum albumin (2.46 vs. 2.78 g/dL) in NE group but increased (P <0.01) (4.70 vs. 4.08 g/dL) and (2.59 vs. 2.04 g/dL), respectively in LE group. High energy birds showed significantly (P <0.01) increased serum albumin (2.74 vs. 2.24 g/dL). The humoral immunity against Newcastle Disease (ND titre) was significantly (P <0.01) higher in 21 days of growth period at both the levels of supplementation but on 42 days no significant difference among the groups were observed. It can be concluded that CoQ10 supplementation at 20 mg/kg decreased blood glucose level and increased erythrocytes osmotic stability and hence, could reduce bird's susceptibility to ascites.
... The carbonylation of proteins was measured as per the method described by Uchida & Stadtman [35]. Co-enzymes Q 9 and Q 10 were appraised employing HPLC as per standard protocol [36]. The level of reduced glutathione (GSH) was assayed by the method described by Hissin & Hilf [37]. ...
Background
Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats.
Methods
SR was chemically characterized by GC-MS analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg, intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level was measured at specific intermissions. Serum biochemical and inflammatory markers were estimated after sacrificing the animals. Besides, myocardial redox status, expressions of signal proteins (NF-κB and PKCs), histological and ultrastructural studies of heart were performed in the controls and SR treated T2D rats.
Results
Phytochemical screening of the crude extract revealed the presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated fatty acids within SR. T2D rats exhibited significantly (p < 0.01) higher fasting blood glucose level with respect to control. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera revealed the occurrence of hyperlipidemia and cell destruction in T2D rats. T2DM caused significant (p < 0.05–0.01) alteration in the biochemical markers in the sera. T2DM altered the redox status (p < 0.05–0.01), decreased (p < 0.01) the intracellular NAD and ATP concentrations in the myocardial tissues of experimental rats. While investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation in nuclear NF-κB (p65) in the cardiac tissues. So, oral administration of SR (50 and 500 mg/kg) could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological and ultra-structural studies of cardiac tissues supported the protective characteristics of SR.
Conclusions
From the present findings it can be concluded that, SR could offer protection against T2DM and its associated cardio-toxicity via multiple mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.
... However, it has to be highlighted that the predominant form of coenzyme Q in rats is CoQ 9 (Gueven et al., 2015). Studies investigating uptake of ingested CoQ 10 in different rat tissues reported that it does not reach the central nervous system (Bentinger et al., 2003;Turunen et al., 1999;Zhang et al., 1995). Although it has been suggested that higher dietary doses can significantly increase CoQ 10 levels in the rat brain (Matthews et al., 1998), it has been shown that even if absorbed, very little CoQ 10 reaches mitochondria (Bentinger et al., 2003). ...
Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron—the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated.
Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.
... Intracellular ATP concentrations were assessed following protocol mentioned in the kit (Abcam, Cambridge, USA). The levels of Co-enzymes Q 9 and Q 10 within the tissue extract were measured by the method of Zhang et al [27]. ...
Background:
Enhydra fluctuans Lour. (Asteraceae), an edible aquatic herb, is traditionally employed against toxic effects of heavy metals in India. The present study was planned to discover the protective effect of edible extract of E. fluctuans (AEEF) against Pb toxicity.
Methods:
The cytoprotective role of AEEF was determined on murine hepatocytes employing MTT assay and Hoechst staining. The effects on lipid peroxidation, protein carbonylation, endogenous redox systems and the transcription levels of apoptotic proteins were studied after incubating the hepatocytes with AEEF (400 μg/ml) + Pb-acetate (6.8 μM). The defensive role of AEEF (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication was measured in mice by in vivo assays. Biochemical, haematological and histological parameters, intracellular Pb burden and redox status were measured.
Results:
AEEF exhibited a concentration dependent cytoprotective effect against Pb-induced cytotoxicity in vitro. Pb-acetate incubation significantly (p < 0.01) altered the extents of ROS production ↑, protein carbonylation ↑, lipid peroxidation ↑, endogenous antioxidant enzymes ↓ and GSH ↓ in vitro. Besides, Pb-acetate significantly (p < 0.01) induced apoptosis in the hepatocytes apparent from the altered expressions of apoptotic proteins viz. Apaf-1 ↑, Bad ↑, Bcl-2 ↓, Cyt C ↑, cleaved caspases↑, Bid ↑ and Fas ↑. However, AEEF (400 μg/ml) could significantly (p < 0.05-0.01) attenuate the Pb-acetate mediated toxic manifestation in vitro. In in vivo assay, Pb-acetate (5 mg/kg) treated mice exhibited significantly (p < 0.01) high intracellular Pb content. A high Pb-burden within the tissues caused significant (p < 0.05-0.01) patho-physiological alterations viz. ROS production ↑, protein carbonylation↑, lipid peroxidation ↑, DNA fragmentation ↑, ATP formation ↑, mitochondrial co-enzymes Q ↓, endogenous antioxidant enzymes ↓ and GSH ↓ within the selected tissues. The haematological and serum biochemical parameters were significantly (p < 0.05-0.01) different in the Pb-acetate treated mice. Finally, histological assessment imposed significant toxic occurrence within the organs of Pb-intoxicated animals. However, concurrent administration of AEEF (100 mg/kg) could significantly (p < 0.05-0.01) reinstate the Pb-acetate mediated toxicity.
Conclusion:
Presence of metal chelators and phyto-antioxidants within AEEF would offer overall protection through promoting Pb clearance coupled with restoring redox balance.
... While tissue CoQ10 levels mainly depend on de novo synthesis, (19) plasma CoQ10 concentrations are significantly influenced by dietary uptake. (20) However, serum or plasma CoQ10 concentrations are frequently used clinically as a raw proxy for the functional CoQ10 status in humans. CoQ10 is considered the main antioxidant in low-density lipoproteins (LDLs). ...
Coenzyme Q10 (CoQ10) is synthesized in almost all human tissues and presumably involved in age-related alterations and diseases. Here, we examined the impact of aging and sex on the serum CoQ10 status in 860 European adults ranging in age from 18 to 82 years. We identified an inverse U-shaped relationship between CoQ10 concentration and age. Women showed lower cholesterol-adjusted CoQ10 levels than men, irrespective of age. As observed in both sexes, the decrease in CoQ10 concentration in older subjects was accompanied by a shift in the redox status in favour of the oxidized form. A strong positive correlation was found for total CoQ10 and cholesterol concentrations (Spearman’s, p≤1E-74). We found strong negative correlations between total (Spearman’s, p≤1E-07) and between cholesterol-adjusted CoQ10 concentration (Spearman’s, p≤1E-14) and the proportion of the oxidized form of CoQ10. These correlations were not dependent on age and sex and were attenuated by supplementation with 150 mg/day reduced CoQ10 for 14 days. Overall, our results are useful to define risk groups with critical CoQ10 status in humans. In particular, older subjects were characterized by impaired CoQ10 status due to their lowered serum CoQ10 concentration and concomitant decrease of CoQ10 redox capacity.
Coenzyme Q10 (CoQ10) is a fat-soluble vitamin analog found in the cells of many organisms, especially in the inner membrane of the mitochondria. Poor bioavailability is one of the limiting factors in the clinical use of CoQ10, which is mainly due to its very low solubility in water. In this regard, in the present study, the micelle nanostructures of CoQ10 and the related parameters were studied with the aim of providing a nanotechnology-based solution to resolve the limitations of CoQ10 and improve physicochemical properties. For this purpose, the glycerol-based Organic phase/Water (O/W) system via bath ultrasonic were used to synthesize CoQ10 nanostructures whereby solubilization descriptors including Micelle-water partition coefficient and free energy of solubilization were calculated. To determine the characteristics of the synthesized nanostructures, UV–Vis, Dynamic light scattering (DLS), Differential Scanning Calorimetry and Thermogravimetric Analysis (DSC-TGA), and SEM electron microscope were used. The results revealed that based on the DLS data, the mean number nanoparticle size was 233 nm and the Poly Dispersity Index was 0.3, which indicates the homogeneity of the Nanostructures. Moreover, the TGA–DSC thermograms demonstrated Nano Micelle Formation. Results proved the glycerol-based CoQ10 Nano micellar system was significantly effective in terms of pharmaco-physical parameters and this nano-based formation can be considered to promote and facilitate the production of Nano Co Q10 as a therapeutical supplement in pharmaceutical industries.
Due to large increases in the elderly populations across the world, age-related diseases are expected to increase dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the properties of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington’s disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.
Coenzyme Q (CoQ, ubiquinone/ubiquinol) is a ubiquitous and unique molecule that drives electrons in mitochondrial respiratory chain and an obligatory step for multiple metabolic pathways in aerobic metabolism. Alteration of CoQ biosynthesis or its redox stage are causing mitochondrial dysfunctions as hallmark of heterogeneous disorders as mitochondrial/metabolic, cardiovascular, and age-associated diseases. Regulation of CoQ biosynthesis pathway is demonstrated to affect all steps of proteins production of this pathway, posttranslational modifications and protein-protein-lipid interactions inside mitochondria. There is a bi-directional relationship between CoQ and the epigenome in which not only the CoQ status determines the epigenetic regulation of many genes, but CoQ biosynthesis is also a target for epigenetic regulation, which adds another layer of complexity to the many pathways by which CoQ levels are regulated by environmental and developmental signals to fulfill its functions in eukaryotic aerobic metabolism.
Coenzyme Q (CoQ) is required for normal metabolic functions in all tissues. In humans, the amount of this lipid increases in all organs during adolescence and reaches its highest peak during the first 2–3 decades of life. At 80 years of age, the amount is decreased to around half. This development is also observed in different regions of the brain. In rodents, a number of physical and chemical factors are known to increase CoQ in various organs. Depending on the type, duration and doses of the treatments applied, the amount of the lipid increased in different organs to variable extents. Vitamin E plays a regulatory role in CoQ synthesis. Low amount of vitamin E in the diet results in lower amount of CoQ in liver and blood, while high amount of this vitamin increase the amount. Several nuclear receptors are involved in the synthesis of the lipid. Mice knockout models of PPARα, RXRα, TRα, and LXRα receptors exhibit significantly reduced amounts of this lipid in the liver and spleen. The amount of CoQ increases in a number of rodent and human pathological conditions, while it decreases in human liver cancer and cardiomyopathy.
The relationship between diet, longevity and health is complex, considering that nutritional components affect several physiologic processes and play a regulatory role in metabolic pathways crucial for the survival of cells. Caloric restriction is well known to extend healthy, average, and maximum life span in an evolutionary conserved way, acting through effector molecules which reprogram energy metabolism in response to reduced energy availability. As a central component in energy metabolism, alterations in coenzyme Q biosynthesis and its cellular balance may participate in adaptive responses to physiological, experimental, or pathological conditions. In fact, coenzyme Q levels, expression of COQ genes and activity of coenzyme Q-dependent antioxidant systems are targets of caloric restriction in a tissue-specific way, with skeletal muscle exhibiting an early response to this intervention. In mammal models, maximal longevity is not affected by life-long administration of coenzyme Q10 when animals are fed normal diets, but dietary coenzyme Q10 supplementation can ameliorate deleterious alterations associated with aging and even extends lifespan of rats fed a potentially prooxidant diet. The role of additional factors, as duration of caloric restriction intervention, caloric restriction protocol, or the predominant fat source present in the experimental diets, among others, is still to be fully determined to understand the actual role of coenzyme Q alterations and their impact on this dietary intervention in relation with the physiology of aging.
Coenzyme Q10 (CoQ10) is an essential component of the electron transport system and the only lipid-soluble compound synthesized endogenously present in all cell membranes with bioenergetics and antioxidant properties. AgingAging, neurodegenerative disorders, cardiovascular disease and other aged-related diseases, as well as genetic mutations, have been associated with CoQ10 deficiency. Since both limited uptake and low bioavailability of dietary CoQ10 might influence in this deficiency, supplementation with CoQ10 must be considered in those cases as therapeutic solution. However, more research is needed in order to identify the appropriate dose, the effectiveness and the bioavailability of orally-administered CoQ10. Furthermore research must be developed in order to design therapeutic agents to induce the endogenous synthesis CoQ10 specially in elderly people. This review will focus in the most relevant biochemical characteristics of this important antioxidantAntioxidants, including its main functions, levels and distribution in human organism and the therapeutic potential of CoQ10, especially, during agingAging and the associated diseases.
A review of the currently available results of experimental and clinical studies of the effectiveness of ubiquinol (a reduced form of coenzyme Q10) under various pathological conditions is presented. First results are indicative of good prospects of the use of ubiquinol as an independent pharmacological agent under pathological conditions associated with oxidative stress.
CoQ10 may assist in managing patients with statin-induced myopathy, in which mitochondrial mechanisms play a significant role, and low CoQ10 levels resulting from inhibition of the mevalonate pathway by statin drugs are reliably raised by CoQ10 administration. CoQ10 may afford partial relief of myalgia in some, but not all, cases. In patients with heart failure, low CoQ10 status predicts a poor outcome, and replacement may improve left ventricular function and lower risk of mortality. CoQ10 replacement is specific therapy for the inherited CoQ10 deficiencies. Large randomized controlled studies of CoQ10 use in heart failure and neurodegenerative diseases are in progress. Many neurological clinics in tertiary hospitals now include CoQ10 in their protocols. In other applications, it is likely the necessary studies to demonstrate efficacy will never take place because CoQ10 is not patentable. A virtual absence of side effects makes CoQ10 use tempting in the many conditions listed in Table 5. For the same reason, a few cardiologists maintain that statins should never be prescribed without also using CoQ10. While CoQ10 is a pedigreed endogenous
Oxidative damage to mitochondria is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic
anti-oxidant, XJB-5-131, which directly targets mitochondria, the primary site and primary target of oxidative damage. XJB-5-131
prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington Disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses
disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes
weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or
improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.
Coenzyme Q10, present in all cells and membranes, is essential for electron transport in the mitochondrial respiratory chain, antioxidant defence, and other functions of great importance for cellular metabolism. The essential advantages of CoQ10, combined with its poor and slow absorption, generated the need to develop new technologies for delivery. Therefore, much effort has been expended to design delivery vehicles that can improve its aqueous solubility and overall bioavailability for oral and topical administration. This chapter summarizes the findings available today concerning CoQ10 chemical characteristics, human functionalities, its impact on human diseases, and new techniques developed to enhance its delivery.
The temporal disappearance of natural antioxidants associated with human low density lipoprotein (LDL) in relation to the appearance of various classes of lipid hydroperoxides was investigated under three types of oxidizing conditions. Freshly isolated LDL from plasma of healthy subjects was free of detectable amounts of lipid hydroperoxides as measured by HPLC postcolumn chemiluminescence detection. Exposure of such LDL to a mild, constant flux of aqueous peroxyl radicals led to rapid and complete oxidation of ubiquinol-10, followed by slower partial depletion of lycopene, beta-carotene, and alpha-tocopherol. After an initial lag period of complete inhibition of detectable lipid peroxidation, formation of hydroperoxides of cholesterol esters, triglycerides, and phospholipids was observed. The onset of detectable lipid peroxidation corresponded closely with the completion of ubiquinol-10 consumption. However, small amounts of ascorbate, present as a contaminant in the LDL preparation, rather than ubiquinol-10 itself were responsible for the initial lag period. Thus, complete consumption of ubiquinol-10 was preceded by that of ascorbate, and exposure of ascorbate-free LDL to aqueous peroxyl radicals resulted in immediate formation of detectable amounts of lipid hydroperoxides. The rate of radical-mediated formation of lipid hydroperoxides in ascorbate-free LDL was low as long as ubiquinol-10 was present, but increased rapidly after its consumption, even though more than 80% and 95% of endogenous carotenoids and alpha-tocopherol, respectively, were still present. Qualitatively similar results were obtained when peroxyl radicals were generated within LDL or when the lipoprotein was exposed to oxidants produced by activated human polymorphonuclear leukocytes. LDL oxidation was reduced significantly by supplementing the lipoprotein preparation with physiological amounts of either ascorbate or ubiquinol-10. Our data show that ubiquinol-10 is much more efficient in inhibiting LDL oxidation than either lycopene, beta-carotene, or alpha-tocopherol.
Just as garlic has long been known to have effective therapeutic and life-prolonging properties, so has exercise. And just as aliin, the active principle of garlic, has resisted discovery until recent times, the scientific basis for the effects of exercise on the human condition is only now in the process of being elucidated. Studies recently published strongly suggest that regular endurance exercise in humans leads to significant improvements in cardiovascular health, resulting in an increase in longevity (1,2). The imminence of the “elderly” catagory by the second author has prompted us to investigate some of the molecular aspects of the effects of endurance exercise in hearts, and other muscles, of aged animals.
The relative rate of biosynthesis of dolichol from [3H]mevalonate in nine rat organs was studied in slices and in the whole animal. This biosynthesis was also compared to that of cholesterol and ubiquinone. All tissues examined are able to synthesize dolichol, as well as ubiquinone and cholesterol. Comparison of the data from slices in vitro with the in vivo studies demonstrated relatively good agreement for dolichol and ubiquinone synthesis. Although dolichol of high specific radioactivity was recovered in the blood, redistribution between organs, such as occurs with cholesterol, appears to be insignificant. The highest rates of dolichol biosynthesis were found in kidney, spleen and liver. On the other hand, muscle makes the largest contribution to total body dolichol synthesis. Newly synthesized dolichol also appears in the bile, but excretion by this route is far from sufficient to account for dolichol turnover.
Incorporation of mevalonate into the final products is mainly dependent on biosynthetic activity. For comparison of the biosynthetic rates in different organs, possible sources of errors (such as variations in the size of the precursor pool, limitation by the rate of precursor uptake or non-linear incorporation) were investigated and corrected for. An isotope-dilution technique was developed and used to demonstrate a sixfold variation in the size of the mevalonate pool in various organs. Equilibration of this pool with exogenous mevalonate is a rapid and passive process. The size of the mevalonate pool does not determine the rates of cholesterol and dolichol biosynthesis, indicating the presence of regulatory steps in the terminal portion of these biosynthetic pathways.
An assay for the separation and detection of lipid hydroperoxides and hydrogen peroxide in biological samples using HPLC and isoluminol chemiluminescence was recently described (Y. Yamamoto, M. H. Brodsky, J. C. Baker, and B. N. Ames (1987)Anal. Biochem.160, 7–13; Y. Yamamoto and B. N. Ames (1987)Free Rad. Biol. Med.3, 359–361). In this paper the application of this assay to the analysis of human blood plasma is described in detail, and three compounds producing chemiluminescence that were observed in the initial studies in plasma extracted with methanol and hexane are further characterized. It is shown that various lipid hydroperoxides added to plasma are detected by the assay. In contrast, hydrogen peroxide added to plasma is rapidly degraded by endogenous catalase. Hydrogen peroxide and a second, minor compound producing chemiluminescence, which appear in the assay of the methanol and the hexane extract of plasma, respectively, appear to be generated during analysis and are not likely to be present in plasma. The third compound yielding a chemiluminescence peak, which is extracted into the hexane phase of plasma and was earlier assigned to cholesterol ester hydroperoxide, is shown to be neither a cholesterol ester nor a hydroperoxide, but the hydroquinone ubiquinol-10. As the chemiluminescence response of hydroperoxides, but not of hydroquinones, is eliminated by reducing reagents such as sodium borohydride or triphenylphosphine, such reduction should be used to confirm that any chemiluminescence producing lipid observed in the assay is a hydroperoxide, not a hydroquinone. We conclude that isolated human plasma from healthy subjects is very unlikely to contain hydrogen peroxide in concentrations greater than about 0.25 μm and does not contain lipid hydroperoxides in concentrations greater than 0.03 μm. The method described, when used with appropriate precautions, is a convenient and very sensitive assay for lipid hydroperoxides in biological tissues.
The half-life of ubiquinone-9 in various rat tissues was determined. Rats were injected intraperitoneally with [3H]mevalonate and the decay of radioactivity incorporated into ubiquinone-9 was followed using reverse-phase HPLC. The half-life varied between 49 h (testis) and 125 h (kidney).
The effects of ubiquinol and vitamin E on ascorbate- and ADP-Fe3+-induced lipid peroxidation were investigated by measuring oxygen consumption and malondialdehyde formation in beef heart submitochondrial particles. In the native particles, lipid peroxidation showed an initial lag phase, which was prolonged by increasing concentrations of ascorbate. Lipid peroxidation in these particles was almost completely inhibited by conditions leading to a reduction of endogenous ubiquinone, such as the addition of succinate or NADH in the presence of antimycin. Lyophilization of the particles followed by three or four consecutive extractions with pentane resulted in a complete removal of vitamin E and a virtually complete removal of ubiquinone, as revealed by reversed-phase high pressure liquid chromatography. In these particles, lipid peroxidation showed no significant lag phase and was not inhibited by either increasing concentrations of ascorbate or conditions leading to ubiquinone reduction. Treatment of the particles with a pentane solution of vitamin E (alpha-tocopherol) restored the lag phase and its prolongation by increasing ascorbate concentrations. Treatment of the extracted particles with pentane containing ubiquinone-10 resulted in a restoration of the inhibition of lipid peroxidation by succinate or NADH in the presence of antimycin, but not the initial lag phase or its prolongation by increasing concentrations of ascorbate. Malonate and rotenone, which prevent the reduction of ubiquinone by succinate and NADH, respectively, abolished, as expected, the inhibition of the initiation of lipid peroxidation in both native and ubiquinone-10-supplemented particles. Reincorporation of both vitamin E and ubiquinone-10 restored both effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Ubiquinones and tocopherols (vitamin E) are intrinsic lipid components which have a stabilizing function in many membranes attributed to their antioxidant activity. The antioxidant effects of tocopherols are due to direct radical scavenging. Although ubiquinones also exert antioxidant properties the specific molecular mechanisms of their antioxidant activity may be due to: (i) direct reaction with lipid radicals or (ii) interaction with chromanoxyl radicals resulting in regeneration of vitamin E. Lipid peroxidation results have now shown that tocopherols are much stronger membrane antioxidants than naturally occurring ubiquinols (ubiquinones). Thus direct radical scavenging effects of ubiquinols (ubiquinones) might be negligible in the presence of comparable or higher concentrations of tocopherols. In support of this our ESR findings show that ubiquinones synergistically enhance enzymic NADH- and NADPH-dependent recycling of tocopherols by electron transport in mitochondria and microsomes. If ubiquinols were direct radical scavengers their consumption would be expected. Further proving our conclusion HPLC measurements demonstrated that ubiquinone-dependent sparing of tocopherols was not accompanied by ubiquinone consumption.
1. The biosynthesis of ubiquinone (UQ) in isolated rat heart under ischemic and hypoxic conditions was investigated. 2. Under ischemic perfusion, a greater amount of biosynthetic intermediates, 3-nonaprenyl and 3-decaprenyl-4-hydroxybenzoate (PPHBs) was accumulated and a smaller amount of UQ-9 and -10 was synthesized when compared with normal conditions. 3. The accumulation of PPHBs was observed without forming UQs during anaerobic perfusion. 4. Hydroxylation which is the following reaction of PPHBs for the biosynthesis of UQ in rat heart, was proceeded by the monooxygenase(s) depending upon the oxygen concentrations.
There is no longer any doubt that high plasma levels of LDL are atherogenic and that lowering them can reduce the risk of coronary heart disease, but the specific events induced by high levels of LDL in the artery wall are only now being elucidated. Once these processes are understood, we may find that there are ways to intervene at the level. Recent advances have brought us closer to being able to do this with regard to the uptake of LDL by macrophages and the development of the fattty streak, the earliest lesion in atherogenesis. Studies both in vitro and in vivo support the hypothesis that LDL undergoes an oxidative modification that targets it for uptake by the macrophage through a specific receptor - the acetyl LDL or scavenger receptor. Intervention studies in the LDL receptor-deficient animal model for atherosclerosis (the WHHL rabbit), using probucol as an antioxidant, show that the progression of the fatty streak can be slowed under conditions that do not lower plasma cholesterol levels. Much more remains to be done to establish the clinical relevance of these findings. Nevertheless, the experimental data available to date encourage aggressive additional research on the oxidative modification of LDL. This review has emphasized the oxidative modification of LDL because the evidence for its occurrence in vivo and for its role in atherogenesis is already persuasive. However, we recognize that with further study additional modifications may prove to be equally important or even more important. For example, the glycation of LDL may help explain the increased susceptibility of diabetic subjects to atherosclerotic complications. If so, rigid control of hyperglycemia may reduce such complications. As we learn more about these and other postsecretory modifications of LDL, we can hope to find ways of preventing them. To the extent that modifications of these kinds play an important part in atherogenesis, we may be able to intervene and obtain protection beyond that obtained by lowering plasma LDL levels.
The levels of cholesterol, ubiquinone, dolichol, dolichyl-P, and total phospholipids in human lung, heart, spleen, liver, kidney, pancreas, and adrenal from individuals from one-day-old to 81 years of age were investigated and compared with the corresponding organs from 2 to 300 day-old rats. The amount of cholesterol in human tissues did not change significantly during aging, but the level of this lipid in the rat was moderately elevated in the organs of the oldest animals. In human pancreas and adrenal the ubiquinone content was highest at one year of age, whereas in other organs the corresponding peak value was at 20 years of age, and was followed by a continuous decrease upon further aging. A similar pattern was observed in the rats, with the highest concentration of ubiquinone being observed at 30 days of age. Dolichol levels in human tissues increase with aging, but they increase to very different extents. In the lungs this increase is seven-fold, and in the pancreas it is 150-fold. The elevation in the dolichol contents of rat tissues ranges from 20 to 30-fold in our material. In contrast, the levels of the phosphorylated derivative of dolichol increased to a more limited extent, i.e., 2 to 6-fold in human tissues and even less in the rat. These results demonstrate that the levels of a number of lipids in human and rat organs are modified in a characteristic manner during the life-span. This is in contrast to phospholipids, which constitute the bulk of the cellular lipid mass.
Rat liver slices were pulse labeled for 6 min with [3H]mevalonolactone and then chased for 90 min with unlabeled mevalonolactone in order to study the mechanism of dolichyl phosphate biosynthesis. The cholesterol pathway was also monitored and served to verify the pulse-chase. Under conditions in which radioactivity in the methyl sterol fraction chased to cholesterol, radioactivity in alpha-unsaturated polyprenyl (pyro)-phosphate chased almost exclusively into dolichyl (pyro)phosphate. Lesser amounts of radioactivity appeared in alpha-unsaturated polyprenol and dolichol, and neither exhibited significant decline after 90 min of incubation. The relative rates of cholesterol versus dolichyl phosphate biosynthesis were studied in rat liver under four different nutritional conditions using labeled acetate, while the absolute rates of cholesterol synthesis were determined using 3H2O. From these determinations, the absolute rates of dolichyl phosphate synthesis were calculated. The absolute rates of cholesterol synthesis were found to vary 42-fold while the absolute rates of dolichyl phosphate synthesis were unchanged. To determine the basis for this effect, the rates of synthesis of cholesterol and dolichyl phosphate were quantitated as a function of [3H]mevalonolactone concentration. Plots of nanomoles incorporated into the two lipids were nearly parallel, yielding Km values on the order of 1 mM. In addition, increasing concentrations of mevinolin yielded parallel inhibition of incorporation of [3H]acetate into cholesterol and dolichyl phosphate. The specific activity of squalene synthase in liver microsomes from rats having the highest rate of cholesterol synthesis was only 2-fold greater than in microsomes from rats having the lowest rate. Taken together, the results suggest that the maintenance of constant dolichyl phosphate synthesis under conditions of enhanced cholesterogenesis is not due to saturation of the dolichyl phosphate pathway by either farnesyl pyrophosphate or isopentenyl pyrophosphate but coordinate regulation of hydroxymethylglutaryl-CoA reductase and a reaction on the pathway from farnesyl pyrophosphate to cholesterol.
Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.
Coenzyme Q (ubiquinone) levels have been determined in rat liver, skeletal muscle, heart muscle, kidney, and brain after various periods of exposure to 0–2 °C. Coenzyme Q is unaffected in brain, but is elevated in other tissues by 2 weeks of cold exposure, reaches a peak at 1 month, and remains elevated for at least 6 months. These results are discussed in relation to the possible role of coenzyme Q in calorigenesis.
Myocardial tissue level of coenzyme QIQ in patients with cardiac failure
- N Kitamura
- A Yamaguchi
- M Otaki
- O Sawatani
- T Minoji
- H Tamuta
- M Atobe
Kitamura, N., Yamaguchi, A., Otaki, M., Sawatani, O., Minoji, T.,
Tamuta, H. & Atobe, M. (1984) Myocardial tissue level of
coenzyme QIQ in patients with cardiac failure. In: Biochemical
and Clinical Aspects of Coenzyme Q (Folkers, K. & Yamamura,
Y., eds.), vol. 4, pp. 243-256. Elsevier, Amsterdam, The Nether
lands.
Regulation of the mevalonate pathway Intracellular distribution of coenzyme Q in rat liver
- J L Goldstein
- M S Brown
Goldstein, J. L. & Brown, M. S. (1990) Regulation of the mevalonate
pathway. Nature (Lond.) 343: 425-430.
fayaraman, J. & Ramasarma, T. (1963) Intracellular distribution of
coenzyme Q in rat liver. Arch. Biochem. Biophys. 103: 258-266.
Cholesierol meiabolism and excrelion. In: The Liver: Biology and Palhobiology
- S D Turley
- J M Dietschy
Turley, S. D. & Dietschy, J. M. (1982) Cholesierol meiabolism and
excrelion. In: The Liver: Biology and Palhobiology (Arias, I.,
Popper, H., Schachter, D. & Shafritz, D. A., eds.), pp. 467-492.
Raven Press, New York, NY.
Clinical perspec tives in treatment of cardiovascular diseases with coenzyme Q
- S A Mortensen
- P Heidt
- J Sehested
Mortensen, S. A., Heidt, P. & Sehested, J. (1990) Clinical perspec
tives in treatment of cardiovascular diseases with coenzyme
Q. In: Highlights in Ubiquinone Research (Lenaz, G., Barnabei, O., Rabbi, A. &. Ballino, M., eds.), pp. 226-227. Taylor &
Francis, London, England.
Tissue concentration of coenzyme QIQ in the rat following ils oral adminisiraiion
- S Reahal
- J Wrigglesworth
Reahal, S. & Wrigglesworth, J. (1992) Tissue concentration
of
coenzyme QIQ in the rat following ils oral adminisiraiion. Drug.
Melab. Disp. 20: 423-427.
Restoration of impaired cardiac function of palienls with muscular dystrophies and neurogenic atrophies by therapy with coenzyme Q\Q-In: Biomédical and Clinical Aspects
- R Simonsen
- K Folkers
- J Komorowski
- A Komorowska
- T Lyson
Simonsen, R., Folkers, K., Komorowski, J., Komorowska, A. &
Lyson, T. (1991) Restoration of impaired cardiac function of
palienls with muscular dystrophies and neurogenic atrophies by
therapy with coenzyme Q\Q-In: Biomédical and Clinical
Aspects of Coenzyme Q (Folkers, K., Litiarru, G. P. &
Yamagami, T., eds.), vol. 6, pp. 363-373. Elsevier, Amsterdam,
The Netherlands.
Dis charge of newly-synthesized dolichol, dolichyl phosphate and ubiquinone with lipoproteins to rat liver perfusate and to the bile
- P G Elmberger
- A Kaien
- U Brunk
- G Dallner
Elmberger, P. G., Kaien, A., Brunk, U. & Dallner, G. (1989) Dis
charge of newly-synthesized
dolichol, dolichyl phosphate and
ubiquinone with lipoproteins to rat liver perfusate and to the
bile. Lipids 24: 919-930.