Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status.

The endogenous biosynthesis of the quinone nucleus of coenzyme Q10 (CoQ10) from tyrosine is dependent on adequate vitamin B6 nutriture. Lowered blood and tissue levels of CoQ10 have been observed in a number of clinical conditions. Many of these clinical conditions are most prevalent among the elderly. Kalen et al. have shown that blood levels of CoQ10 decline with age. Similarly, Kant et al. have shown that indicators of vitamin B6 status also decline with age. Blood samples were collected from 29 patients who were not currently being supplemented with either CoQ10 or vitamin B6. Mean CoQ10 concentrations was 1.1 +/- 0.3 micrograms/ml of blood. Mean specific activities of EGOT was 0.30 +/- 0.13 mumol pyruvate/hr/10(8) erythrocytes and the mean percent saturation of EGOT with PLP was 78.2 +/- 13.9%. Means for all parameters were within normal ranges. Strong positive correlation was found between CoQ10 and the specific activity of EGOT (r = 0.5787, p < 0.001) and between CoQ10 and the percent saturation of EGOT with PLP (r = 0.4174, p < 0.024). Studies are currently in progress to determine the effect of supplementation with vitamin B6 of blood CoQ10 levels. It appears prudent to recommend that patients receiving supplemental CoQ10 be concurrently supplemented with vitamin B6 to provide for better endogenous synthesis of CoQ10 along with the exogenous CoQ10.     

Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults

Oxidative modification of low-density lipoprotein (LDL) may cause arterial endothelial dysfunction in hyperlipidemic subjects. Antioxidants can protect LDL from oxidation and therefore improve endothelial function. Dietary supplementation with coenzyme Q (CoQ(10)) raises its level within LDL, which may subsequently become more resistant to oxidation. Therefore, the aim of this study was to assess whether oral supplementation of CoQ(10) (50 mg three times daily) is effective in reducing ex vivo LDL oxidizability and in improving vascular endothelial function. Twelve nonsmoking healthy adults with hypercholesterolemia (age 34+/-10 years, nine women and three men, total cholesterol 7.4+/-1.1 mmol/l) and endothelial dysfunction (below population mean) at baseline were randomized to receive CoQ(10) or matching placebo in a double-blind crossover study (active/placebo phase 4 weeks, washout 4 weeks). Flow-mediated (FMD, endothelium-dependent) and nitrate-mediated (NMD, smooth muscle-dependent) arterial dilatation were measured by high-resolution ultrasound. CoQ(10) treatment increased plasma CoQ(10) levels from 1.1 +/-0.5 to 5.0+/-2.8 micromol/l (p =.009) but had no significant effect on FMD (4.3+/-2.4 to 5.1+/-3.6 %, p =.99), NMD (21.6+/-6.1 to 20.7+/-7.8 %, p = .38) or serum LDL-cholesterol levels (p = .51). Four subjects were selected randomly for detailed analysis of LDL oxidizability using aqueous peroxyl radicals as the oxidant. In this subgroup, CoQ(10) supplementation significantly increased the time for CoQ(10)H(2) depletion upon oxidant exposure of LDL by 41+/-19 min (p = .04) and decreased the extent of lipid hydroperoxide accumulation after 2 hours by 50+/-37 micromol/l (p =.04). We conclude that dietary supplementation with CoQ(10) decreases ex-vivo LDL oxidizability but has no significant effect on arterial endothelial function in patients with moderate hypercholesterolemia.     

Coenzyme Q concentration and total antioxidant capacity of human milk at different stages of lactation in mothers of preterm and full-term infants

Coenzyme Q10(CoQ10) in human milk at different stages of maturity in mothers of preterm and full-term infants and its relation to the total antioxidant capacity of milk is described for the first time. Thirty healthy breastfeeding women provided colostrum, transition-milk and mature-milk samples. Coenzyme Q, alpha-, gamma- and delta-tocopherol, fatty acids and the total antioxidant capacity of the milk were analyzed. Coenzyme Q10 was found at higher concentrations for colostrum (0.81+/-0.06 vs. 0.50+/-0.05 micromol/l) and transition milk (0.75+/-0.06 vs. 0.45+/-0.05 micromol/l) in the full-term vs. the preterm group (similar results were found for total antioxidant capacity). Concentrations of alpha- and gamma-tocopherol were higher in the full-term group and decreased with time. In conclusion, CoQ10 is present in breast milk, with higher concentration in mothers of full-term infants. CoQ10 in breast milk decreases through lactation in mothers delivering full-term infants. Also, CoQ10, alpha- and gamma-tocopherol concentration in human milk directly correlates with the antioxidant capacity of the milk.     

Chronic administration of coenzyme Q<Subscript>10</Subscript> limits postinfarct myocardial remodeling in rats

The effect of chronic coronary artery occlusion on the content of rat myocardial coenzymes Q (CoQ) and evaluation of the applicability of CoQ(10) for limiting postinfarct remodeling have been investigated. Left ventricle myocardium hypertrophy was characterized by the decrease in CoQ(9) (-45%, p < 0.0001), CoQ(10) (-43%, p < 0.001), and alpha-tocopherol (-35%, p < 0.05). There were no differences between the parameters of postinfarction and sham-operated rats in plasma. Administration of CoQ(10) (10 mg/kg) via a gastric probe for 3 weeks before and 3 weeks after occlusion maintained higher levels of CoQ in the postinfarction myocardium: the decrease in CoQ(9) and CoQ(10) was 25% (p < 0.05) and 23% (p < 0.05), respectively (versus sham-operated animals). Plasma concentrations of CoQ(10) were more than 2 times higher (p < 0.05). In CoQ treated rats there was significant correlation between plasma levels of CoQ and the infarct size: r = -0.723 (p < 0.05) and r = -0.839 (p < 0.01) for CoQ(9) and CoQ(10). These animals were also characterized by earlier and more intensive scar tissue formation in the postinfarction myocardium and also by more pronounced cell regeneration processes. This resulted in the decrease in both the infarct size (16.2 +/- 8.1 vs. 27.8 +/- 12.1%) and also mass index of left ventricle (2.18 +/- 0.24 vs. 2.38 +/- 0.27 g/kg) versus untreated rats (p < 0.05). Thus, long-term treatment with ubiquinone increases plasma and myocardial CoQ content and this can improve the survival of myocardial cells during ischemia and limit postinfarct myocardial remodeling.     

A superior analysis of coenzyme Q10 in blood of humans, rabbits and rats for research

The quantitative analysis of coenzyme Q10 (CoQ10) in samples of whole human blood has been refined to allow a 2- to 3-fold increase in the number of analyses per day, and reduction of cost to approximately 15% of the previous cost. The method is simple yet maintains reliability. The standard error was 0.2% (n = 6). The variation in blood levels of CoQ10 for human subjects for each of three months was approximately 5% in comparison with the control value (n = 5). For 30 human males, of 18-50 years (26 +/- 6) in age, and for 30 human females, of 18-50 years (26 +/- 9), the mean blood level of CoQ10 was 0.71 +/- 0.13 microgram/ml and 0.70 +/- 0.18 microgram/ml respectively. The mean blood levels of CoQ10 of rabbits (n = 28) was 0.29 +/- 0.07 micrograms/ml, and that for rats (n = 29) was 0.23 +/- 0.03 micrograms/ml.     

A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies

Two situations required a modified determination of coenzyme Q10 (CoQ10) in human blood and organ tissue. Blood from patients with AIDS and cancer raised apprehensions about safety to an analyst, and the number of specimens for analysis is increasing enormously. A modified determination replaces silica gel-TLC with disposable Florisil columns, and steps were simplified to allow more analyses per unit time. Data from the modified determination are quantitatively compatible with data from older and tedious procedures. This determination was used for blood from 36 diverse patients with allergies. The mean CoQ10 blood level of these patients is not different from the mean level of so-called normal individuals, but approximately 40% (14/36) of these allergic patients had levels up to 0.65 micrograms/ml, which is the level of dying class IV cardiac patients. The biosynthesis of CoQ10 in human tissues is a complex process that requires several vitamins and micronutrients, so that countless vitamin-unsupplemented Americans may be deficient in CoQ10. The relationship of allergies to autoimmune mechanisms and immunity, and the established relationship of CoQ10 to immune states, may be a rationale for therapeutic trials of administering CoQ10 to patients with allergies who have low CoQ10 blood levels and are very likely deficient.     

Significance of biological parameters of human blood levels of CoQ10

Ninety-one men and 143 women who were so-called normal subjects were tested for cardiac performance at rest and their blood levels of co-enzyme Q10 (CoQ10) were determined. In males, a negative relationship between progression of age and cardiac performance, and a positive relationship between progression of age and blood levels of CoQ10 were revealed. In females, a positive relationship between age and blood levels of CoQ10 was found. The mean CoQ10 blood level for both sexes was the same (0.79 +/- 0.20 micrograms/ml for males and 0.79 +/- 0.23 for females). Cardiac performance declines with age in the male population. A decreased biosynthesis and/or incorporation of CoQ10 into mitochondrial structures of muscle cells may occur with age in a normal population.     

Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure

BACKGROUND: There is evidence that plasma CoQ(10) levels decrease in patients with advanced chronic heart failure (CHF). OBJECTIVE: To investigate whether oral CoQ(10) supplementation could improve cardiocirculatory efficiency in patients with CHF. METHODS: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 +/- 9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 +/- 7%), using a double-blind, placebo-controlled cross-over design. Patients were assigned to oral CoQ(10) (100 mg tid) and to placebo for 4 weeks, respectively. RESULTS: CoQ(10) supplementation resulted in a threefold increase in plasma CoQ(10) level (P < 0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ(10) supplementation (+12.1 and 15.6%, respectively, P < 0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P < 0.0001) in relation to a decrease in LV end-systolic volume index (from 57 +/- 7 mL/m(2) to 45 mL/m(2), P < 0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ(10) levels (r = -0.52, P < 0.005). Peak VO(2) was also improved after CoQ(10) as compared with placebo (+13%, <0.005). No side effects were reported with CoQ(10). CONCLUSIONS: Oral CoQ(10) improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity.     

Effects of the anaesthetic/tranquillizer treatments on selected plasma biochemical parameters in NZW rabbits

In order to assess the response of plasma biochemical parameters to anaesthesia, 40 New Zealand White (NZW) rabbits were assigned to four treatment groups (n = 10): control (1 ml i.v. saline solution), fentanyl-droperidol (FD) (0.4 ml/kg s.c. of 'thalamonal' solution; 2.5 mg/ml droperidol, 0.05 mg/ml fentanyl), ketamine (K) (10 mg/kg i.v.) with either xylazine (X) (3 mg/kg i.v.) or diazepam (D) (2 mg/kg i.v.). Blood samples were obtained from the central ear artery at six time points: before injection, and at 10, 30, 60, 120 min and 24 h after injection of the anaesthetics/saline. Plasma ALT, AST, ALP, GGT, BUN, creatinine, phosphate and potassium levels were measured by the Hitachi 747 autoanalyser. The administration of K-X increased (P < 0.05) plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.7 IU/l, at 10 min), AST (from 10.5 +/- 3.3 to 34 +/- 2.1 IU/l, at 120 min), BUN (from 17.2 +/- 0.9 to 25.8 +/- 1.8 mg/dl, at 60 min) and creatinine concentrations (from 1 +/- 0.1 to 1.6 +/- 0.2 mg/dl, at 10 min). After K-D administration, we observed an increase (P < 0.05) in plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.1 IU/l, at 10 min), AST (from 11.4 +/- 1.6 to 28 +/- 3.7 IU/l, at 10 min), BUN (from 15.8 +/- 0.8 to 30 +/- 1.5 mg/dl, at 10 min) and creatinine levels (from 1 +/- 0.08 to 2.2 +/- 0.2 mg/dl, at 120 min). No significant changes were seen in the FD group. We conclude that K-X and K-D may affect plasma concentration of select serum enzymes and biochemical parameters. These results should be taken into account when blood samples are evaluated in treated rabbits.     

Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore

Coenzyme Q10 (CoQ10) is an essential biological cofactor which increases brain mitochondrial concentration and exerts neuroprotective effects. In the present study, we exposed SHSY5Y neuroblastoma cells to neurotoxic beta amyloid peptides (Abeta) and oxygen glucose deprivation (OGD) to investigate the neuroprotective effect of 10 microM CoQ10 by measuring (i) cell viability by the MTT assay, (ii) opening of the mitochondrial permeability transition pore via the fluorescence intensity of calcein-AM, and (iii) superoxide anion concentration by hydroethidine. Cell viability (mean +/- S.E.M.) was 55.5 +/- 0.8% in the group exposed to Abeta + OGD, a value lower than that in the Abeta or OGD group alone (P < 0.01). CoQ10 had no neuroprotective effect on cell death induced by either Abeta or OGD, but increased cell survival in the Abeta + OGD group to 57.3 +/- 1.7%, which was higher than in the group treated with vehicle (P < 0.05). The neuroprotective effect of CoQ10 was blocked by administration of 20 microM atractyloside. Pore opening and superoxide anion concentration were increased in the Abeta + OGD group relative to sham control (P < 0.01), and were attenuated to the sham level (P > 0.05) when CoQ10 was administered. Our results demonstrate that CoQ10 protects neuronal cells against Abeta neurotoxicity together with OGD by inhibiting the opening of the pore and reducing the concentration of superoxide anion.     

Serum 5-androstene-3 beta,17 beta-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche

Serum sex hormone binding globulin (SHBG), testosterone (T), DHEA sulphate (DHEA-S), androstenedione (AD) and delta 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S) levels were measured by specific radioimmunoassay in 16 girls presenting with premature adrenarche (PA) and in 14 normal girls. Mean levels of steroids measured were elevated, and SHBG significantly depressed, in the girls with PA, with values (mean +/- SE) for DHEA-S (1.73 +/- 0.17 vs 0.25 +/- 0.06 mumol/l), 5-ADIOL-S (104 +/- 8 vs 31 +/- 4 nmol/l), AD (0.89 +/- 0.06 vs 0.62 +/- 0.04 nmol/l), and T (0.49 +/- 0.03 vs 0.23 +/- 0.06 nmol/l). SHBG levels were 68 +/- 6 vs 108 +/- 5 nmol/l, and the free androgen index [100 x T (nmol/l) divided by SHBG (nmol/l)] was 0.89 +/- 0.17 vs 0.22 +/- 0.01. These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue. This may be compounded by the elevated levels of 5-ADIOL-S in girls with PA since its role may be as a prohormone for more potent androgens (testosterone, 5 alpha-dihydrotestosterone) in target tissues such as pubic skin.     

Coenzyme Q(10) in submicron-sized dispersion improves development, hatching, cell proliferation, and adenosine triphosphate content of in vitro-produced bovine embryos.

Coenzyme Q(10) (CoQ(10)) is an essential component of the plasma membrane ion transporter (PMIT) system and of the electron transport chain in the inner mitochondrial membrane. Because of its intrinsic functions in cell growth and energy metabolism (ATP synthesis), and its protective effects against oxidative stress, CoQ(10) is a good candidate for supporting growth of cells in culture. However, because of its quinone structure, CoQ(10) is extremely lipophilic and practically insoluble in water. We used a specific technology to prepare a submicron-sized dispersion of CoQ(10), inhibiting re-crystallization by a stabilizer. This dispersion, which exhibits a very large specific surface area for drug dissolution, was tested as a supplement for the in vitro culture of bovine embryos in a chemically defined system. The rate of early cleavage of embryos (5- to 8-cell stages) was evaluated 66 h postinsemination (hpi) and was highest in medium supplemented with 30 or 100 microM CoQ(10) (66.5 +/- 0.8% and 68.7 +/- 1.1%, respectively) and lowest in 10 microM CoQ(10) (55.3 +/- 0.8%). The proportions of oocytes developing to blastocysts by 186 hpi were 19.0 +/- 0.6% and 25.2 +/- 0.3% in medium supplemented with 10 microM and 30 microM CoQ(10), respectively, and were significantly (p < 0.001) higher than those obtained with the equivalent amounts of stabilizer (9.9 +/- 0.4% and 11.3 +/- 0.4%). In the presence of 30 microM CoQ(10), significantly (p < 0.001) more blastocysts hatched by 210 hpi than in the equivalent amount of stabilizer (31.8 +/- 1.3 vs. 8.4 +/- 2.2). Expanded blastocysts produced in the presence of 30 microM CoQ(10) had significantly (p < 0.01) more inner cell mass cells and trophectoderm cells, and a significantly (p < 0.001) increased ATP content as compared to expanded blastocysts produced in the presence of the corresponding amount of stabilizer. Our results show that noncrystalline CoQ(10) in submicron-sized dispersion supports the development and viability of bovine embryos produced in a chemically defined culture system.     

Effect of naturally occurring isothiocyanates in the inhibition of cyclophosphamide-induced urotoxicity.

Cyclophosphamide-induced urotoxiciy was reduced in Swiss albino mice by the treatment of naturally occurring isothiocyanates such as AITC or PITC (25 microg/dose/animal, i.p.) for 5 days along with CTX (1.5 mmol/kg body wt.; i.p.). Severely inflamed and dark coloured urinary bladders of the CTX alone treated animals were found to be normalized on morphological analysis by the treatment of AITC or PITC. Urine protein levels were reduced by the treatment with AITC (6.2 +/- 0.37 g/l) and PITC (6.56 +/- 1.56 g/l), which was elevated by CTX administration (8.66 +/- 0.47 g/l). Urine urea N2 that was enhanced significantly by CTX administration (26.87 +/- 1.86 g/l) was reduced by treatment with both AITC (17.38 +/- 0.06 g/l) and PITC (15.85 +/- 1.56 g/l). GSH content, which was drastically reduced by CTX administration in both bladder (0.87 +/- 0.1 nmol/mg protein) and liver (2.47 +/- 0.6 nmol/mg protein) was enhanced by treatment with AITC and PITC both in bladder (AITC- 3.65 +/- 0.18 nmol/mg protein; PITC- 2.8 +/- 0.15 nmol/mg protein) and in liver (AITC- 4.10 +/- 0.81 nmol/mg protein; PITC- 4.70 +/- 0.44 nmol/mg protein). Histopathology of the bladders of CTX alone treated group showed severe necrosis of the tissue whereas AITC and PITC treated group showed normal bladder pathology.     

Serum FSH levels during estrus and a 4-week period following mating in Murrah buffaloes (Bubalus bubalis )

Circulating FSH levels of 13 Murrah buffaloes were investigated by a double-antibody radioimmunoassay using a homologous bovine system. The mean (+/- s.e.m.) peak FSH level on the day of estrus was if57.94 +/- 12.84 ng/ml of blood serum during hotter months (June-August) and 65.23+/-10.54 ng/ml during cooler months (October-December). These were much higher than the FSH concentrations recorded during the rest of the cycle post-mating. There were sizable fluctuations in FSH levels on different days of the estrous cycle within animals. However, the mean values did not exhibit much variation. The occurrence of the FSH peak and the LH peak coincided during the cycle.     

CoQ10 supplementation elevates the epidermal CoQ10 level in adult hairless mice

We have already shown that prolonged supplementation of CoQ(10) in humans reduces the wrinkle area rate and wrinkle volume per unit area in the corner of the eye. CoQ(10) supplementation is known to increase the CoQ(10) level in serum and in many organs; however, the level of CoQ(10) in skin has not yet been fully investigated yet. We examined whether CoQ(10) intake elevates the CoQ(10) and CoQ(9) levels in epidermis, dermis, serum and other organs (kidney, heart, brain, muscle and crystalline lens) in 43-week-old hairless male mice. We also established a method using a high performance liquid chromatograph equipped with an electrochemical detector (HPLC-ECD) to simultaneously quantify CoQ(9) and CoQ(10) in the tissues. CoQ(10) (0, 1, 100 mg/kg p.o.) was administered daily for 2 weeks. CoQ(10) supplementation of 100 mg/kg increased the serum and epidermal CoQ(10) levels significantly, but did not increase the CoQ(10) levels in either dermis or other organs. In conclusion, we showed that CoQ(10) intake elevates the epidermal CoQ(10) level, which may be a prerequisite to the reduction of wrinkles and other benefits related to the potent antioxidant and energizing effects of CoQ(10) in skin.     

Coenzyme Q10 evaluation in pituitary-adrenal axis disease: preliminary data

In previous works we have demonstrated plasma CoQ10 alterations in pituitary diseases, such as acromegaly or secondary hypothyroidism. However, pituitary lesions can induce complex clinical pictures due to alterations of different endocrine axes controlled by pituitary itself. A further rationale for studying CoQ10 in pituitary-adrenal diseases is related to the common biosynthetic pathway of cholesterol and ubiquinone. We have therefore assayed plasma CoQ10 levels in different conditions with increased or defective activity of pituitary-adrenal axis (3 subjects with ACTH-dependent adrenal hyperplasia, 2 cases of Cushing's disease and 1 case of 17-alpha-hydroxylase deficiency; 10 subjects with secondary hypoadrenalism, including three subjects with also secondary hypothyroidism). CoQ10 levels were significantly lower in isolated hypoadrenalism than in patients with adrenal hyperplasia and multiple pituitary deficiencies (mean +/- SEM: 0.57 +/- 0.04 vs 1.08 +/- 0.08 and 1.10 +/- 0.11 microg/ml, respectively); when corrected for cholesterol levels, the same trend was observed, but did not reach statistical significance. These preliminary data indicate that secretion of adrenal hormones is in some way related to CoQ10 levels, both in augmented and reduced conditions. However, since thyroid hormones have an important role in modulating CoQ10 levels and metabolism, when coexistent, thyroid deficiency seems to play a prevalent role in comparison with adrenal deficiency.     

Estimation of plasma and saliva levels of coenzyme Q10 and influence of oral supplementation

Coenzyme Q10 (CoQ(10)) levels in human saliva were measured by HPLC with a highly sensitive electrochemical detector (ECD) and a special concentration column. This HPLC system showed satisfactory analytical results within the standard range of 0.78-50 ng/ml. We also found a significant correlation between CoQ(10) levels in plasma and in saliva from parotid glands, while this correlation was lacking between plasma CoQ10 and CoQ10 in whole saliva. Unlike in plasma, there are some fluctuations of saliva CoQ(10) levels throughout the day. A good correlation was obtained by collecting parotid gland saliva at times between meals. The mean saliva CoQ(10) level for 55 healthy volunteers was 17.0 ng/ml (S.D. 6.8 ng/ml); approximately one fiftieth of that in plasma. Regarding the influence of oral supplementation, CoQ(10) was analyzed in plasma and parotid gland saliva from 20 healthy volunteers supplemented daily with 100 mg of CoQ(10) for the first week and 200 mg for the second. The plasma CoQ(10) levels of all volunteers increased to different extents in accordance with the CoQ(10) daily intake and the corresponding change in saliva showed almost the same trend.     

Determination of carotenoid and vitamin A concentrations in everted salmonid intestine following exposure to solutions of carotenoid in vitro

Carotenoid (astaxanthin and canthaxanthin) concentrations in everted intestine from rainbow trout (Oncorhynchus mykiss, Walbaum) and Atlantic salmon (Salmo salar, L.) exposed to micelle solubilised carotenoid, have been determined. Following exposure (1 h) to astaxanthin solution (5 mg l(-1)), trout pyloric caeca and mid intestine had higher (P<0.05) mean tissue astaxanthin concentrations (0.50+/-0.08 microg g(-1) and 0.54+/-0.09 microg g(-1), respectively) compared to hind intestine (0.04+/-0.01 microg g(-1); n=11+/-S.E.). Furthermore, the astaxanthin concentration in pyloric caeca (0.50+/-0.08 microg g(-1)) was greater (P<0.05) than that of canthaxanthin (0.11+/-0.01 microg g(-1); n=11, +/-S.E.) when exposed to solutions of similar carotenoid concentration (5.11+/-0.16 mg l(-1) and 5.35+/-0.16 mg l(-1), respectively; n=3+/-S.E.). However, no differences (P>0.05) were recorded between trout and salmon intestinal tissue in terms of astaxanthin concentration following exposure. Trout caeca exposed to astaxanthin solution had significantly (P<0.05) more vitamin A (514.1+/-36.4 microg g(-1)) compared to control tissues (316.5+/-61.7 microg g(-1); n=8+/-S.E.). Vitamin A(1) concentrations in caeca (287.7+/-11.0 microg g(-1)) exposed to astaxanthin solution were significantly higher (P<0.05) compared to controls (174.9+/-26.9 microg g(-1)). However, vitamin A(2) concentrations were not significantly (P>0.05) different (226.3+/-28.2 microg g(-1) and 141.6+/-35.2 microg g(-1), respectively).     

A sensitive liquid chromatographic method for the spectrophotometric determination of urinary trans,trans-muconic acid

Benzene is a human carcinogen and its metabolite, urinary trans,trans-muconic acid (ttMA), is a biomarker for risk assessment. However, most of the existing methods were not sensitive enough for monitoring of low level exposure. This paper describes a HPLC-UV method for ttMA determination with enhanced selectivity and sensitivity. A 30 mg OasisMAX cartridge was used to clean-up 50 microl of urine sample and gradient elution was performed on a Zorbax SB-C(18) column (30 degrees C). ttMA was detected at wavelength 263 nm using a UV diode array detector (DAD). The two mobile phases used were (A) 150 mM ortho-phosphoric acid containing of 9% (v/v) methanol; and (B) 125 mM ortho-phosphoric acid containing 30% (v/v) acetonitrile. The method was validated with 61 urine samples collected from non-occupationally benzene exposed individuals and 14 quality control specimens from an international quality assessment scheme. The urinary ttMA concentrations (mean+/-S.D.microg/g creatinine) were 90+/-34 for smokers (n=26), 49+/-39 for non-smokers (n=21) and 23+/-18 for non-smoking hospital staff (n=14). A correlation coefficient, r=0.99 was found with 14 external quality specimens for ttMA ranged from 0.4 to 6.8 mg/l. The recovery and reproducibility were generally over 90% and the detection limit was 5 microg/l.     

Bioenergetic effect of liposomal coenzyme Q10 on myocardial ischemia reperfusion injury.

The antioxidant and bioenergetic effects of CoQ10 are well known but its clinical utility is limited by the requirement for enteral administration. A newly developed liposomal CoQ10 (CoQ) is water soluble and capable of intravenous administration. The purpose of this study is to determine the mechanism by which acute administration CoQ protects myocardium from reperfusion (Rp) injury. Rats were pretreated with CoQ 10 mg/kg i.v. 30 min prior to the experiment. Control rats were pretreated with liposome only. Hearts were excised and subjected to equilibration, 25 min of normothermic ischemia and 40 min of Rp on a Langendorff apparatus. At end Rp, CoQ hearts recovered 74 +/- 5% of their DP vs. 50 +/- 9% in control (p < 0.05). Aerobic efficiency was maintained (0.66 +/- 0.02 vs. control, 0.5 +/- 0.04, p < 0.003) and CoQ hearts lost less CK activity vs. control (p < 0.02). PCr and ATP were higher than control (p < 0.05, 0.02, respectively). Results show that i.v. CoQ improves recovery of function, aerobic efficiency, CK activity, and recovery of PCr and ATP after Rp. This suggests that acute administration of liposomal CoQ improves myocardial tolerance to I/R via its role as an antioxidant as well as improving oxygen utilization and high energy phosphate production.