Rat Plasma Proteins Research Articles

Molecular property–binding affinity relationship of flavonoids for common rat plasma proteins in vitro

The structural difference of flavonoids strongly affects the binding process with plasma proteins. This work in here mainly concerns about the molecular property–binding affinity relationship of dietary flavonoids for common rat plasma proteins (CRPP). The magnitudes of binding constants between flavonoids and CRPP were within the range of 10 4–10 5 L/mol and the number of binding sites ( n) was determined as 1.02 ± 0.19. These data were much smaller than the affinities between flavonoids and purified bovine and human serum albumins. The hydroxylation on rings A, B and C of flavonoids significantly affected the binding affinity. The glycosylation of dietary flavonoids decreased the binding affinity and the C2 C3 double bond hardly affected it. The galloylated catechins have higher binding affinities for CRPP than non-galloylated catechins. Flavonoids played as a hydrogen bond acceptor when bound to CRPP. The flavonoids with high topological polar surface areas (TPSA) are bound tightly while those with low TPSA are not.

Plasma and liver proteomic analysis of 3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one-induced hepatotoxicity in Wistar rats

3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24), a synthetic anti-angiogenic compound, inhibits the growth and metastasis of certain tumors. Previous works have shown that Z24 induces hepatotoxicity in rodents. We examined the hepatotoxic mechanism of Z24 at the protein level and looked for potential biomarkers. We used 2-DE and MALDI-TOF/TOF MS to analyze alternatively expressed proteins in rat liver and plasma after Z24 administration. We also examined apoptosis in rat liver and measured levels of intramitochondrial ROS and NAD(P)H redox in liver cells. We found that 22 nonredundant proteins in the liver and 11 in the plasma were differentially expressed. These proteins were involved in several important metabolic pathways, including carbohydrate, lipid, amino acid, and energy metabolism, biotransformation, apoptosis, etc. Apoptosis in rat liver was confirmed with the terminal deoxynucleotidyl transferase dUTP-nick end labeling assay. In mitochondria, Z24 increased the ROS and decreased the NAD(P)H levels. Thus, inhibition of carbohydrate aerobic oxidation, fatty acid beta-oxidation, and oxidative phosphorylation is a potential mechanism of Z24-induced hepatotoxicity, resulting in mitochondrial dysfunction and apoptosis-mediated cell death. In addition, fetub protein and argininosuccinate synthase in plasma may be potential biomarkers of Z24-induced hepatotoxicity.

Pharmacokinetics of magnolin in rats

This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the V ( ss ) after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3-76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3-80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were dose-independent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed.

LC-ESI-MS-MS Determination of Rat Plasma Protein Binding of Major Flavonoids of Flos Lonicerae Japonicae by Centrifugal Ultrafiltration

Centrifugal ultrafiltration (CU) and a fast liquid chromatography with electrospray ionization tandem mass spectrometric (LC-ESI-MS-MS) method have been developed for drug-protein binding analysis of four flavonoids of Flos Lonicerae Japonicae (FLJ). A rapid separation of free drug from the plasma was achieved by CU and the simultaneous analysis of four flavonoids of FLJ in rat plasma was by fast LC-ESI-MS-MS. The chromatographic analytical time decreased to 6.5 min without sacrificing resolution using a 4.6 mm × 50 mm, 1.8 μm particle size reverse phase column and MS–MS mode performed for multiple reaction monitoring (MRM). The protein binding rates of four flavonoids were in the range of 66.8 ± 7.4 to 81.3 ± 5.1% after oral administration of the flavonoid fraction of FLJ. All values were almost similar to 70.0% at 30, 45 and 80 min. Its result suggests that these flavonoids in rat plasma perform high protein binding rates and present a stable binding in a longer time. Meanwhile, it reveals that the elimination of these flavonoids may be relatively moderate in the body, the performance of a certain degree of accumulation may be speculated and make further impacts on the pharmacokinetic parameters.

Protective role of L-ascorbic acid against cypermethrin-induced oxidative stress and lipid peroxidation in Wistar rats

Cypermethrin is a synthetic pyrethroid insecticide used for pest control in agriculture and as an acaricide in man and animals. This study was undertaken with the objective to investigate the propensity of cypermethrin to induce oxidative stress in rats following repetitive dermal exposure and its possible attenuation by L-ascorbic acid. Results obtained showed that cypermethrin significantly (p < 0.05) increased malonaldehyde levels, activity of catalase in rat erythrocytes and plasma protein levels. Whereas, activities of glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were significantly (p < 0.05) reduced in the cypermethrin exposed rats as compared to the control. Supplementation of L-ascorbic acid in cypermethrin-exposed rats decreased lipid peroxidation of erythrocytes, total plasma protein and catalase activity significantly (p < 0.05) compared to non-cypermethrin-exposed group. However, L-ascorbic acid did not alleviate the negative effects of cypermethrin on the activities of SOD and GSH. This study revealed that the presence of L-ascorbic acid diminishes the adverse effects of cypermethrin on some oxidative stress parameters.

Effect of soya bean diet preparations on some haematological and biochemical indices in the rat

Effects of Soya bean diet preparations on the hematocrit, hemoglobin concentration, total plasma protein, plasma albumin, sodium, potassium and chloride concentrations were studied in male albino rats. The animals were fed diets containing 75%, 50% and 25% Soya bean in groups II, III and IV respectively. Group I rats served as the control and were fed normal mouse cubes. There were steady but significant increases in the concentrations of hematocrit, hemoglobin, total plasma protein and plasma albumin in rats fed 25% to 75% concentration of Soya bean in the diets .Although there were significant increases in the electrolytes concentrations between the Soya bean diets and rats fed normal diet, there was no significant difference in the electrolytes concentrations of rats fed different concentrations of Soya bean. This study therefore seems to confirm the nutritional value of Soya bean in alleviating malnutrition

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor.

To better develop N-[4-(benzoylamino)phenylsulfonyl]glycine (BAPSG), a potent and selective aldose reductase inhibitor capable of delaying the progression of ocular diabetic complications, the objective of this study was to assess its pharmacokinetics. The plasma pharmacokinetics of BASPG was assessed in male Sprague-Dawley rats following intravenous, intraperitoneal and oral routes of administration and its distribution to various tissues including those of the eye was studied following intraperitoneal administration. In addition, rat plasma protein binding of BAPSG was studied using ultracentrifugation method and its ocular tissue disposition was assessed following topical administration in rabbits. Plasma and tissue levels of BAPSG were analysed using an HPLC assay. BAPSG exhibited dose-proportionate AUC0 --> infinity (area under the plasma concentration-time curve) following both intravenous and intraperitoneal administration over the dose range (5-50 mg kg(-1)) studied and an erratic oral absorption profile with low oral bioavailability. The fraction bioavailability following oral and intraperitoneal administration was 0.06 and 0.7-1, respectively. BAPSG exhibited short plasma elimination half-lives in the range 0.5-1.5 h. BAPSG was bound to rat plasma proteins and the percent protein binding ranged from 83 to 99.8%. BAPSG was better distributed to cornea, lens and retina than to brain, following intraperitoneal administration in rats. However, the distribution was lower compared with kidney and liver. Following topical administration in rabbits, BAPSG delivery to the surface ocular tissues, cornea and conjunctiva was higher compared with intraocular tissues, aqueous humour, iris-ciliary body and lens. Thus, BAPSG was distributed to ocular tissues following systemic and topical modes of administration.

Sex-specific concentrations of plasma proteins in rats determined by sex hormones in perinatal life.

The present investigation examined the relationship between concentrations of plasma proteins in oestrogen-primed adult rats and sex hormone concentrations in neonatal life. alpha 2-acute phase globulin (alpha 2-AP) and female specific protein (FP) were found to be higher in adult females than in adult males. Androgen administration in females on the first day of life declined permanently these protein concentrations, while neonatal castration in males on the first or third day of life resulted in a permanent increase in FP concentration. Both the alpha 2-AP and FP response in adulthood to hormonal stimulation is dependent on the androgen level during a critical neonatal organization period.

Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor α agonist in preclinical species and human

5-{2-[4-(3,4-Difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid (1) is a novel, potent, and selective agonist of the peroxisome proliferator-activated receptor alpha (PPAR-α).In preclinical species, compound 1 demonstrated generally favourable pharmacokinetic properties. Systemic plasma clearance (CLp) after intravenous administration was low in Sprague–Dawley rats (3.2 ± 1.4 ml min−1 kg−1) and cynomolgus monkeys (6.1 ± 1.6 ml min−1 kg−1) resulting in plasma half-lives of 7.1 ± 0.7 h and 9.4 ± 0.8 h, respectively. Moderate bioavailability in rats (64%) and monkeys (55%) was observed after oral dosing. In rats, oral pharmacokinetics were dose-dependent over the dose range examined (10 and 50 mg kg−1).In vitro metabolism studies on 1 in cryopreserved rat, monkey, and human hepatocytes revealed that 1 was metabolized via oxidation and phase II glucuronidation pathways. In rats, a percentage of the dose (approximately 19%) was eliminated via biliary excretion in the unchanged form.Studies using recombinant human CYP isozymes established that the rate-limiting step in the oxidative metabolism of 1 to the major primary alcohol metabolite M1 was catalysed by CYP3A4.Compound 1 was greater than 99% bound to plasma proteins in rat, monkey, mouse, and human.No competitive inhibition of the five major cytochrome P450 enzymes, namely CYP1A2, P4502C9, P4502C19, P4502D6 and P4503A4 (IC50’s > 30 μM) was discerned with 1.Because of insignificant turnover of 1 in human liver microsomes and hepatocytes, human clearance was predicted using rat single-species allometric scaling from in vivo data. The steady-state volume was also scaled from rat volume after normalization for protein-binding differences. As such, these estimates were used to predict an efficacious human dose required for 30% lowering of triglycerides.In order to aid human dose projections, pharmacokinetic/pharmacodynamic relationships for triglyceride lowering by 1 were first established in mice, which allowed an insight into the efficacious concentrations required for maximal triglyceride lowering. Assuming that the pharmacology translated in a quantitative fashion from mouse to human, dose projections were made for humans using mouse pharmacodynamic parameters and the predicted human pharmacokinetic estimates.First-in-human clinical studies on 1 following oral administration suggested that the human pharmacokinetics/dose predictions were in the range that yielded a favourable pharmacodynamic response.

Pharmacokinetics, tissue distribution and mass balance of radiolabeled dihydroartemisinin in male rats

BackgroundDihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans.MethodsPharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples.ResultsDrug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [14C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h).ConclusionIn rat brain, the total concentration of [14C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion and multiple concentration peaks of DHA have been demonstrated with high urinary excretion due to a most likely drug re-absorption in the intestines (enterohepatic circulation). The long lasting metabolites of DHA (> 192 hr) in the rats may be also related to the enterohepatic circulation.

Analysis of plasma protein in newborn rats treated with diethylstilbestrol by using rapid micro two-dimensional electrophoresis

We examined the effect of diethylstilbestrol(DES) administration on newborn male rats by rapid micro two-dimensional polyacrylamide gel electrophoresis (RM2D-PAGE) under non-denaturing/denaturing conditions and a 10-17% second-dimensional gel. We began by visually analyzing the changes at each week over time (weeks 1-9) in plasma protein spots from the same individual DES-administered male rats. We found the tendency for mercaptoalbumin (reduced form) spots to increase in week 1 in DES-administered rats. We also analyzed the quantitative alterations in α2u-globulin (AUG), a biomarker of endocrine disruptors, and found a two-week delay in expression in DES-administered rats in comparison to those not given DES (control rats). We then investigated the reproducibility of these results by using samples taken from multiple male rats in weeks 5, 7 and 9 to perform electrophoretic analysis three times for each individual, and observed the changes in AUG. AUG production was not seen in week 5 in the control rats, but was present at weeks 7 and 9. In DES-administered rats, expression was not observed at week 5 or 7, but was present at week 9. In addition, we identified the spots of AUG by Western blotting after electrophoresis. We consequently confirmed that AUG production delayed by two weeks in DES-administered rats, in comparison with control rats, which suggests that the effect of either a decline in AUG synthesis function or its depletion results in stunting of the reproductive organs, which was confirmed through autopsy.

Stereoselective plasma protein binding and target tissue distribution of clausenamide enantiomers in rats

Stereoselective differences in pharmacokinetics between clausenamide (CLA) enantiomers have been found after intravenous and oral administration of each enantiomer to rats. The differences could be associated with protein binding of CLA enantiomers. By equilibrium dialysis methods, the binding of CLA enantiomers to rat plasma protein was investigated. The results showed that mean percentages of (-) and (+)CLA in the bound form were 28.5% and 38.0%, respectively, indicating that the unbound fraction of (-)CLA was higher than that of (+)CLA, which provided an explanation for stereoselective pharmacokinetics of CLA enantiomers in rats. The results also showed that there were species differences in plasma protein binding of (-)-isomer between rats (28.5%) and rabbits (47.2%). Furthermore, effects of plasma protein binding on the distribution of CLA enantiomers to their possible target tissues were observed. The amount of (-)CLA in brain was greater than that of (+)CLA 15 min after administration of each enantiomer to rats. But the results were reverse at 4 h postdose. Further studies in distributional kinetics showed that (-)CLA had a more rapid absorption and distribution to hippocampus, cortex, and cerebellum than (+) CLA. (+)CLA had greater values for T(max), t(1/2) (beta), and AUC(0) (-->infinity), and smaller ones for CL/F and V(d)/F than its antipode. The data indicated that the distribution of (-) and (+)CLA in their target tissues was stereoselective. The stereoselective distribution might be involved in the metabolism and transport of two enantiomers in the central nerve system.

Identification of oxidized proteins in rat plasma using avidin chromatography and tandem mass spectrometry

Identification of oxidized proteins in rat plasma using avidin chromatography and tandem mass spectrometry

Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts Scientific Opinion of the Panel on Contaminants in the Food chain.

Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts Scientific Opinion of the Panel on Contaminants in the Food chain.

Identification of oxidized proteins in rat plasma using avidin chromatography and tandem mass spectrometry

The objective in much of the proteomics literature today is to establish the difference between healthy and disease states at the protein level using blood plasma. A critical component in this endeavor is to establish what is normal. The focus of the work reported here was to do this with oxidized proteins that might relate to oxidative stress and oxidative stress-related diseases. Oxidative stress is known to increase markedly in cancer, diabetes, heart disease, and neurodegenerative diseases. Since proteins are one of the targets of ROS, generated by oxidative stress, oxidized proteins are excellent biomarker candidates for these diseases. But first it is necessary to identify oxidized proteins that occur in the healthy state. Healthy rat plasma was used in this study as a source for the identification of naturally oxidized proteins. Freshly drawn blood was treated with biotin hydrazide to selectively derivatize carbonyl groups in oxidized proteins. Oxidized proteins thus biotinylated were separated from the other plasma proteins using avidin affinity chromatography. Affinity selected proteins were further fractionated on a C(8) RP column and fractions collected. The collected fractions were then tryptic digested and the peptides identified using a combination of LC/MS/MS and database searches. One hundred forty-six proteins were identified using 700 signature peptides from the tryptic digested chromatographic fractions. The most frequently encountered proteins in the samples were keratins. Brain and liver were among the organs contributing the most oxidized proteins to plasma followed by heart and kidney.

Pharmacokinetics of salvianolic acids after intravenous injection, with and without Panax quinquefolium protopanaxadiol saponins, in rats

Aim The purpose of the present study was to examine the effects of Panax quinquefolium protopanaxadiol saponins (PQDS) extracts on the plasma protein binding and pharmacokinetic of salvianolic acids extracts extracted from the traditional Chinese medical Salvia miltiorrhiza,. Salvianolic acids are used to treat myocardial ischemia, and PQDS has similar functions. It is expected to achieve a better therapeutic efficacy if the two extracts are developed as a compound prescription for injection. Materials and methods An established high-performance liquid chromatographic technique coupled with microdialysis was used. Male Sprague–Dawley rats were given salvianolic acids extracts and a compound of the two extracts via femoral vein. Results It was found that there were significant differences in the percentage protein binding as well as the pharmacokinetic parameters. The rat plasma protein binding of the four salvianolic acids increased by different degrees at three dose levels (25, 50, 100mg/kg of salvianolic acid B) when the two extracts were administered together. Also, their elimination half-life was prolonged, and their plasma concentrations remained stable longer after administration of a dose of 50mg/kg (salvianolic acid B). Conclusions The results indicated that the PQDS extracts could delay the excretion of salvianolic acids as well as maintain the blood concentration higher than salvianolic acids extracts administered alone.

Identification of the Major Arsenic-Binding Protein in Rat Plasma As the Ternary Dimethylarsinous−Hemoglobin−Haptoglobin Complex

Chronic exposure to arsenic causes a wide range of diseases such as hyperkeratosis, cardiovascular diseases, and skin, lung, and bladder cancers, and millions of people are chronically exposed to arsenic worldwide. However, little is known about the mechanisms underlying these toxic actions. The metabolism of arsenic is essential for understanding the toxic actions. Here, we identified the major arsenic-binding protein (As-BP) in the plasma of rats after oral administration of arsenite by the use of two different HPLC columns, gel filtration and anion exchange ones, coupled with an inductively coupled argon plasma mass spectrometer (ICP MS). The molecular mass of the As-BP was estimated to be 90 kDa based on results using the former column, and arsenic bound to this protein only in the form of dimethylarsinous acid (DMA (III)) in the plasma in vivo. In addition, the purified As-BP was shown to consist of two different proteins, haptoglobin (Hp) of 37 kDa (three bands) and the hemoglobin (Hb) alpha chain of 14 kDa (single band), using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), respectively, suggesting that the As-BP was the ternary DMA (III)-Hb-Hp complex. To confirm the present observations, an arsenic-binding assay was carried out in vitro . Although DMA (III) bound directly to fresh rat plasma proteins, they were different from that identified in vivo. However, when a DMA (III)-exposed rat RBC lysate (DMA (III) binds to Hb in rat RBCs) was added to control rat plasma, a new arsenic peak increased at the expense of the arsenic-Hb one. Furthermore, this new arsenic peak was consistent with the As-BP identified in the plasma in vivo, suggesting that arsenic bound to Hb further binds to haptoglobin (Hp), forming the ternary As-Hb-Hp complex.

Effects of Oral Administration of Aspirin and Paracetamol on Plasma and Brain Protein, Tryptophan Levels and Monoamine Oxidase Activity in Rats

Effects of Oral Administration of Aspirin and Paracetamol on Plasma and Brain Protein, Tryptophan Levels and Monoamine Oxidase Activity in Rats

Analysis of plasma protein adsorption onto PEGylated nanoparticles by complementary methods: 2‐DE, CE and Protein Lab‐on‐chip® system

The biodistribution of colloidal carriers after their administration in vivo depends on the adsorption of some plasma proteins and apolipoproteins on their surface. Poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to cross the blood-brain barrier (BBB) by a mechanism of endocytosis. In order to clarify this mechanism at the molecular level, proteins and especially apolipoproteins adsorbed at the surface of PEG-PHDCA nanoparticles were analyzed by complementary methods such as CE and Protein Lab-on-chip in comparison with 2-D PAGE as a method of reference. Thus, the ability of those methodologies to identify and quantify human and rat plasma protein adsorption onto PEG-PHDCA nanoparticles and conventional PHDCA nanoparticles was evaluated. The lower adsorption of proteins onto PEG-PHDCA nanoparticles comparatively to PHDCA nanoparticles was evidenced by 2-D PAGE and Protein Lab-on-chip methods. CE allowed the quantification of adsorbed proteins without the requirement of a desorption procedure but failed, in this context, to analyze complex mixtures of proteins. The Protein Lab-on-chip method appeared to be very useful to follow the kinetic of protein adsorption from serum onto nanoparticles; it was complementary to 2-D PAGE which allowed the identification (with a relative quantification) of the adsorbed proteins. The overall results suggest the implication of the apolipoprotein E in the mechanism of passage of PEG-PHDCA nanoparticles through the BBB.

Modifications of plasma proteome in long-lived rats fed on a coenzyme Q 10-supplemented diet

Dietary coenzyme Q 10 prolongs life span of rats fed on a PUFA n-6-enriched diet. Our aim was to analyze changes in the levels of plasma proteins of rats fed on a PUFA n-6 plus coenzyme Q 10-based diet. This approach could give novel insights into the mechanisms of life span extension by dietary coenzyme Q 10 in the rat. Serum albumin, which decreases with aging in the rat, was significantly increased by coenzyme Q 10 supplementation both at 6 and 24 months. After depletion of the most abundant proteins by affinity chromatography, levels of less abundant plasma proteins were also studied by using 2D-electrophoresis and MALDI-TOF mass fingerprinting analysis. Our results have shown that lifelong dietary supplementation with coenzyme Q 10 induced significant decreases of plasma hemopexin, apolipoprotein H and inter-α-inhibitor H4P heavy chain (at both 6 and 24 months), preprohaptoglobin, fibrinogen γ-chain precursor, and fetuin-like protein (at 6 months), and α-1-antitrypsin precursor and type II peroxiredoxin (at 24 months). On the other hand, coenzyme Q 10 supplementation resulted in significant increases of serine protease inhibitor 3, vitamin D-binding protein (at 6 months), and Apo A–I (at 24 months). Our results support a beneficial role of dietary coenzyme Q 10 decreasing oxidative stress and cardiovascular risk, and modulating inflammation during aging.