Biomedical subjects

R Stocker

Publications and source records attributed to R Stocker.

At least 163 records · Page 9Linked to original sources

PubMed1994

[Patient management in polytrauma with injuries of the cervical spine].

Complex unstable cervical spine injuries in polytraumatized patients are stabilized ventro-dorsally in a two-stage procedure. The ventral stabilization is a day-one surgery with the goal to get primary stability for intensive care, early spinal decompression and protection against secondary damage of the spinal cord. The additional dorsal stabilization allows early functional treatment or in case of spinal cord lesions early neurorehabilitation. The combination of severe brain injury and unstable cervical spine injury is especially demanding concerning diagnostic and therapeutic procedures.

Adolescent↗

PubMed1993

Bilirubin attenuates radical-mediated damage to serum albumin.

Oxidative damage to biological macromolecules has been implicated in a number of diseases. Much interest has focused on how non-proteinaceous, low-molecular weight antioxidants prevent oxidative damage to lipids, while comparatively little is known about protein antioxidation. Here we show that bilirubin (BR), the end-product of heme catabolism, when bound to bovine serum albumin (BSA), is oxidised by hydroxyl (.OH), hydroperoxyl (HO2.), and superoxide anion (O2-.) radicals to so far mostly uncharacterised products. The initial oxidation rates of BSA-bound BR decreased in the order OH > HO2. > O2-.. BR protected its carrier protein from oxidative damage inflicted by .OH radicals. This protective action included a reduction in the .OH-mediated cleavage of BSA, conversion of Trp into kynurenine and formation of 'bityrosine-specific' fluorescence. BR also strongly inhibited .OH-mediated formation of protein carbonyls, whereas ascorbate and Trolox (a water-soluble analogue of vitamin E) were much less effective. These results support an antioxidant-protective function of BR and point towards significant differences in the efficacies of various antioxidants in the prevention of oxidative damage to lipids and proteins.

Antioxidants↗

PubMed1993

Greater selective uptake by Hep G2 cells of high-density lipoprotein cholesteryl ester hydroperoxides than of unoxidized cholesteryl esters.

We have observed recently that high-density lipoproteins (HDL) are the predominant carriers of cholesteryl ester hydroperoxides (CEOOH), the major class of lipid hydroperoxides detectable at nanomolar concentrations in the plasma of healthy fasting humans. The present study investigates the effect of such very low levels of CEOOH in apolipoprotein E-free HDL3 on lipoprotein particle metabolism and 'selective uptake' of its CE by human Hep G2 cells. Minimal oxidation with aqueous peroxyl radicals had a negligible effect on the binding, internalization and degradation of 125I-labelled HDL3. In contrast, with an increasing degree of radical-mediated oxidation of labelled HDL3, [3H]cholesteryl linoleate ([3H]Ch18:2) was taken up at an increasingly greater rate than were 125I-apoproteins. When [3H]cholesteryl linoleate hydroperoxide ([3H]Ch18:2-OOH was incorporated into unoxidized HDL3 by exchange from donor liposomes, it was taken up at a more than 8-fold higher rate than was incorporated [3H]Ch18:2. The same degree of preferential uptake of oxidized CE was observed when HDL3 was used that was doubly labelled with [3H]Ch18:2-OOH and cholesteryl [14C]oleate ([14C]Ch18:1). In both situations, uptake of [3H]Ch18:2-OOH exceeded that of 125I-apolipoprotein A-I some 40-fold. This increased selective uptake of [3H]Ch18:2-OOH from very mildly oxidized HDL3 was accompanied by a parallel increase in the intracellular levels of labelled free cholesterol. In contrast, lipid hydroperoxides were not detectable within Hep G2 cells, suggesting efficient detoxification of CEOOH by these cells. Neither the increased selective uptake of Ch18:2-OOHs nor the levels of intracellular free cholesterol were influenced by the presence of 50 microM chloroquine, suggesting extralysosomal hydrolysis of oxidized CEs. These results show that the selective uptake of HDL CEOOH by Hep G2 cells is more efficient than that of unoxidized CE, and support a protective role for rapid selective uptake in the removal of circulating HDL CEOOH.

Biological Transport↗

PubMed1993

The oxidation of blood plasma and low density lipoprotein components by chemically generated singlet oxygen.

Human blood plasma and freshly isolated LDL were exposed to singlet oxygen (1O2) by thermal decomposition of synthetic endoperoxides. Exposure of blood plasma to 20 mM water-soluble 1O2 generator resulted in the depletion of ascorbate (100%), urate (75%), ubiquinol-10 (65%), protein thiols (50%), and bilirubin (25%), whereas under these conditions the levels of alpha-tocopherol, beta-carotene, and lycopene remained unchanged. The following rates of depletion were obtained by kinetic analysis (moles depleted per 100 mol of 1O2 consumed): protein thiols (5), urate (5), ascorbate (4), bilirubin (1), and ubiquinol-10 (0.008). In contrast, the rates of depletion using the lipid-soluble 1O2 generator were faster for bilirubin (13-fold), protein thiols (9-fold), ubiquinol-10 (8-fold), and ascorbate (5-fold), and slower for urate (2-fold). The formation of lipid hydroperoxides, including mostly cholesteryl linoleate hydroperoxide, was observed in 1O2-treated plasma (0.007-0.009 mol/100 mol 1O2) and LDL solutions (0.086 mol/100 mol 1O2). Based on competition kinetics, we estimate that 98% of 1O2 generated in the aqueous phase of plasma is quenched by components in this phase, mostly by plasma protein (63%; 6% by protein thiols), urate (9%; 5% by chemical quenching), and bilirubin (5%; 1% by chemical quenching). Ascorbate and ubiquinol-10 do not contribute to 1O2 quenching in plasma, and their oxidation is probably mediated secondary species. The remaining 1O2 generated in plasma (2%) diffuses into lipoprotein leading to the formation of lipid hydroperoxides with an efficiency of about 100-fold greater than that compared to aqueous generated 1O2. The principal 1O2 quenchers in LDL include apoB (42%), lycopene and beta-carotene (40%), and alpha-tocopherol (17%). The importance of carotenoids in the quenching of 1O2 in lipoprotein suggest that the beneficial effects of these compounds in health may in part be due to the elimination of this species in biology and medicine.

Adult↗

PubMed1993

Extracellular reduction of ubiquinone-1 and -10 by human Hep G2 and blood cells.

Ubiquinol-10 (CoQ10H2) is present in human low density lipoproteins (LDL) where it contributes significantly to the antioxidant defenses against radical-mediated oxidative damage. As CoQ10H2 becomes oxidized to ubiquinone-10 (CoQ10) during the earliest stages of in vitro oxidation of LDL, we investigated a possible cellular recycling of oxidized CoQ10H2, adding CoQ10 or its ambiphilic, short-chain analogue ubiquinone-1 (CoQ1), to cells that are exposed to LDL in vivo. Whole blood, isolated red blood cells and human hepatoma Hep G2 cells (used as a model of hepatocytes) rapidly and efficiently reduced added CoQ1 to ubiquinol-1 (CoQ1H2) detectable outside the cells. In whole blood the same steady-state level of CoQ1H2 was reached whether an equimolar amount of CoQ1 or CoQ1H2 was added. Red cell membranes also showed some reducing activity, whereas CoQ1 added to human blood plasma remained largely in its oxidized form. Cell- and membrane-mediated reduction of CoQ1 was enhanced by NADH, FAD, or human plasma. In comparison to this rapid reduction of extracellular CoQ1, formation of CoQ10H2 from CoQ10 incorporated into human LDL by red blood and Hep G2 cells was slow. Our results show that although human blood cells and Hep G2 cells are endowed with a highly reducing activity for CoQ1, the natural CoQ10 does not appear to represent an efficient substrate for this activity.

Adult↗

PubMed1993

Redox metabolism of vitamin C in blood of normal and malaria-infected mice.

As oxidative mechanisms have been suggested to be part of the host immune reaction against malarial parasites, we investigated the redox metabolism of the antioxidant vitamin C in the blood of control and malaria-infected mice. At the peak of infection (day 6) with the malaria parasite P. vinckei, plasma levels of ascorbate (AH-) were 10.8 +/- 0.9 micrograms/ml compared to 5.7 +/- 0.7 micrograms/ml in control mice, though no significant change was observed in the plasma concentration of dehydroascorbate (DHA). The plasma redox ratio of vitamin C, [AH-]:[DHA], was 7.4 in control mice and 18.5 in infected mice on day 6 post-inoculation. The increased AH- level in plasma of P. vinckei-infected mice was not due to differences in stabilities of either AH- or DHA in plasmas from control or P. vinckei-infected mice. DHA added to plasma was lost rapidly. In contrast, when added to whole blood. DHA was rapidly taken up and reduced to AH by blood cells from both normal mice and P. vinckei-infected mice. Most of the intracellular AH- derived from the exogenously added DHA was released into the plasma by blood cells from the infected but not normal mice. The observed release of AH- into the plasma by blood cells from infected mice was not caused by a plasma factor. Depletion of leukocytes from erythrocytes had no effect on the uptake and reduction of DHA by red blood cells, but the subsequent release of intracellular AH- occurred more rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants.

Exposure of proteins to oxygen-centred radicals results in dramatic changes in their structure, stability and function; properties that have been studied in many laboratories from a qualitative viewpoint. To allow a quantitative evaluation, we subjected aerated solutions of BSA to hydroxyl and superoxide anion radicals generated radiolytically under conditions where all radicals formed reacted with the protein (as judged by maximum damage to BSA). We observed that for each radical generated approx. 15 amino acids were consumed initially. Similar results were found with lysozyme and melittin. Such a massive consumption of BSA's amino acids was not observed when irradiations were carried out under anaerobic conditions. When bilirubin or Trolox (a water-soluble analogue of vitamin E) was added at a 2-fold molar excess over BSA, initial consumption of all measured amino acids, except tryptophan, decreased 4-fold. The total mass of amino acids initially protected (from consumption) exceeded the mass of antioxidants consumed by more than a factor of 20. Such protection of amino acids was not observed when the antioxidant-inactive acetyl Trolox was used. These results suggest that radical-mediated oxidation of proteins can proceed via a previously unrecognized chain reaction that may be inhibited by chain-breaking antioxidants.

Amino Acids↗

PubMed1993

[Hemodynamic improvement during therapy using the intravascular oxygenator (IVOX)].

The intravascular oxygenator (IVOX) is a new device which is implanted in the vena cava sup. and inf. where it oxygenates the blood and removes CO2. We report on its successful use in a young patient with severe pneumonia. This 21-year-old female was admitted to hospital with acute respiratory distress due to pneumococcal pneumonia and sepsis following chickenpox. Considering the rapidly progressive course with severe hypoxia and shock, PaO2/PaCO2 values of 6.5/6.4 kPa on mechanical ventilation with an FiO2 of 1.0 and a PEEP of 13 mbar, we decided to implant an intravascular oxygenator. Besides rapid improvement of oxygenation, we observed remarkable recovery of cardiovascular function such as an increase in mean arterial pressure and mixed-venous saturation, while the dose of vasopressors could be decreased. The intravascular oxygenator was removed without problems after 29 days of continuous use, when pulmonary function allowed an FiO2 of 0.45. The patient was discharged from the intensive care unit after 99 days in a good neurological and stable cardiovascular state.

Adult↗

PubMed1993

Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins.

The antioxidant activity of tocotrienols toward peroxyl radicals was compared with that of other natural lipid-soluble antioxidants in three different systems by measuring the temporal disappearance of antioxidants and the formation of lipid hydroperoxides. In homogeneous solution, the initial rates of consumption of the various antioxidants, assessed by competition experiments between pairs of antioxidants for radicals, decreased in the order: ubiquinol-10 approximately ubiquinol-9 > alpha-tocopherol approximately alpha-tocotrienol > beta-carotene approximately lycopene > gamma-tocopherol approximately gamma-tocotrienol. Following in vitro incubation of human plasma with alpha-tocotrienol, this form of vitamin E was present in all classes of lipoproteins isolated from the supplemented plasma. Dietary supplementation of rats and humans with a tocotrienol-rich preparation resulted in a dose-dependent appearance of alpha- and gamma-tocotrienols in plasma and all circulating lipoproteins, respectively. Exposure of such enriched rat plasma to aqueous peroxyl radicals resulted in simultaneous consumption of the alpha- and then gamma-isomers of vitamin E. The sequence of radical-induced consumption of antioxidants in freshly isolated, in vitro and in vivo tocotrienol-enriched low density lipoprotein (LDL) was again ubiquinol-10 > alpha-tocotrienol approximately alpha-tocopherol > carotenoids > gamma-tocopherol approximately gamma-tocotrienol. Under conditions where radicals were generated at constant rates, the rate of lipid hydroperoxide formation in LDL was not constant. It proceeded in at least three stages separated by the phase of ubiquinol-10 consumption and, subsequently, that of alpha-tocopherol/alpha-tocotrienol. Our results show that dietary tocotrienols become incorporated into circulating human lipoproteins where they react with peroxyl radicals as efficiently as the corresponding tocopherol isomers.

Adult↗

PubMed1993

Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages.

Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein.

Acetylation↗

PubMed1993

Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein.

Recent studies on the initial stages in oxidation of low density lipoprotein (LDL) have revealed certain previously unrecognized similarities to emulsion polymerization and some quite unexpected features including the following: (i) ascorbate is an extremely effective antioxidant for LDL containing alpha-tocopherol (alpha-TOH); (ii) in the presence of alpha-TOH and in the absence of both ascorbate and ubiquinol 10 (Q10H2), oxidation of LDL occurs via a free radical chain; (iii) Q10H2 is a much better antioxidant for LDL than alpha-TOH, although the reverse is true in homogeneous systems. We show here that these problems can be solved on the basis of three simple hypothesis, each of which is based on known chemistry: (i) alpha-TOH in LDL can be regenerated from its radical, alpha-TO., by ascorbate; (ii) in the absence of ascorbate and Q10H2, the alpha-TOH in LDL acts as a chain-transfer agent rather than as a radical trap; (iii) Q10H2 is a much more effective chain-breaking antioxidant than alpha-TOH in LDL because the semiquinone radical Q10H. exports its radical character from the LDL into the aqueous phase. Our conclusions imply that the search for better antiatherosclerotic drugs might profitably focus on antioxidants capable of exporting radicals from LDL particles or otherwise increasing the traffic of radicals between particles.

Antioxidants↗

PubMed1993

Circulating lipid hydroperoxide levels in human hyperhomocysteinemia. Relevance to development of arteriosclerosis.

Elevated circulating homocyst(e)ine is a risk factor for occlusive vascular disease. We explored whether elevated plasma homocyst(e)ine is associated with increased plasma lipid hydroperoxides that might trigger vascular disease. We obtained plasma containing high levels of homocyst(e)ine from four patients with a homozygous deficiency of cystathionine beta-synthase activity and also from four heterozygotes with a deficiency of this enzyme after an oral methionine load. The mean plasma non-protein-bound homocyst(e)ine level in all subjects was more than 11-fold higher than the mean normal fasting value. Levels of high density lipoprotein (HDL) cholesteryl ester hydroperoxides (CEOOH), normalized against the concentration of free cholesterol in HDL, were not elevated in our subjects (mean +/- SD, 0.0091 +/- 0.0061) compared with values for 14 fasting healthy donors (0.0164 +/- 0.0086). An inverse dependency was observed between plasma total homocyst(e)ine and HDL CEOOH (r = -0.78, p = 0.023). Also, the ubiquinol-10/ubiquinone-10 ratio in HDL, which is expected to fall during oxidative stress, increased with plasma homocyst(e)ine. Since HDL contains the majority of detectable plasma lipid hydroperoxides, of which CEOOHs are the most abundant, our data suggest that an elevated plasma homocyst(e)ine level does not enhance oxidative stress, increase the levels of lipid hydroperoxides in plasma, or generate vascular damage by this mechanism.

Adult↗

PubMed1993

[Management of patient data in an intensive care unit with Macintosh and Filemaker Pro--extra effort or facilitation of routine care with improved information flow?].

A documentation system for patients in ICU is presented. The programming is based on Filemaker Pro from Claris. Two files have been created: the first "1 Eintritt" contains all the patients data like name, address, the patients history, diagnosis, therapies as the planned procedures. All these data can be imported into the second file "2 KG Unfallchirurgie" with a personal identification number. Complications, new results or further procedures can be added. Different layouts allow the user to print summaries or duty reports. The experience with 300 patients showed, that this system is easy to learn and to use, that it has a good compliance with the medical staff and that is gains a lot of time writing summaries or reports used for transferring patients to other units.

Attitude of Health Personnel↗

PubMed1992

Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant.

Uptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atherosclerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease. However, a careful examination of lipid peroxidation in LDL induced by a steady flux of aqueous peroxyl radicals has demonstrated that, following consumption of endogenous ubiquinol-10, the rate of peroxidation (i) declines as vitamin E is consumed, (ii) is faster in the presence of vitamin E than following its complete consumption, (iii) is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or by diet, and (iv) is virtually independent of the applied radical flux. We propose that perodixation is propagated within lipoprotein particles by reaction of the vitamin E radical (i.e. alpha-tocopheroxyl radical) with polyunsaturated fatty acid moieties in the lipid. This lipid peroxidation mechanism, which can readily be rationalized by the known chemistry of the alpha-tocopheroxyl radical and by the radical-isolating properties of fine emulsions such as LDL, explains how reagents which reduce the alpha-tocopheroxyl radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL.

Fatty Acids, Unsaturated↗

PubMed1992

High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors.

Analysis of untreated fresh blood plasma from healthy, fasting donors revealed that high density lipoprotein (HDL) particles carry most (approximately 85%) of the detectable oxidized core lipoprotein lipids. Low density lipoprotein (LDL) lipids are relatively peroxide-free. In vitro the mild oxidation of gel-filtered plasma from fasting donors with a low, steady flux of aqueous peroxyl radicals initially caused preferential oxidation of HDL rather than LDL lipids until most ubiquinol-10 present in LDL was consumed. Thereafter, LDL core lipids were oxidized more rapidly. Isolated lipoproteins behaved similarly. Preferential accumulation of lipid hydroperoxides in HDL reflects the lack of antioxidants in most HDL particles compared to LDL, which contained 8-12 alpha-tocopherol and 0.5-1.0 ubiquinol-10 molecules per particle. Cholesteryl ester hydroperoxides (CEOOHs) in HDL and LDL were stable when added to fresh plasma at 37 degrees C for up to 20 hr. Transfer of CEOOHs from HDL to LDL was too slow to have influenced the in vitro plasma oxidation data. Incubation of mildly oxidized LDL and HDL with cultured hepatocytes afforded a linear removal of CEOOHs from LDL (40% loss over 1 hr), whereas a fast-then-slow biphasic removal was observed for HDL. Our data show that HDL is the principal vehicle for circulating plasma lipid hydroperoxides and suggest that HDL lipids may be more rapidly oxidized than those in LDL in vivo. The rapid hepatic clearance of CEOOHs in HDL could imply a possible beneficial role of HDL by attenuating the build-up of oxidized lipids in LDL.

Adult↗

PubMed1992

The participation of nitric oxide in cell free- and its restriction of macrophage-mediated oxidation of low-density lipoprotein.

The potential role of nitric oxide radical (NO .) in macrophage-mediated oxidation and conversion of human low density lipoprotein (LDL) to a high-uptake form was examined by exposing LDL to aerobic solutions of either NO . or 3-morpholino-sydnonimine-hydrochloride (SIN-1, a compound that spontaneously forms NO . and superoxide anion radical) or to mouse peritoneal macrophages in the presence and absence of modulators of cellular NO . synthesis. Incubation with NO . alone caused oxidation of LDL's ubiquinol-10 and accumulation of small amounts of lipid hydroperoxides, but failed to form any high-uptake ligand for endocytosis by macrophages and did not alter the LDL particle charge or the integrity of apoB. Exposure of LDL to SIN-1 resulted in complete consumption of all antioxidants and substantial formation of lipid hydroperoxides, but again had little effect on the lipoprotein particle charge or generation of high-uptake form. Preincubation of macrophages with interferon-gamma increased the cells ability to generate reactive nitrogen metabolites. The extent of cell-mediated oxidation of LDL and the generation of high-uptake LDL was substantial in resident cells in which NO . synthesis was barely detectable, depressed in cells active in NO . synthesis and restored when NO . synthesis was suppressed by the arginine analogue, NMMA. These results suggest that, while together with superoxide anion radical, NO . can oxidize LDL, its synthesis is not required for macrophage-mediated oxidation of LDL in vitro; rather it exerts a protective role in preventing oxidative LDL modification by macrophages.

Animals↗

PubMed1992

Oxidation of 3-hydroxyanthranilic acid to the phenoxazinone cinnabarinic acid by peroxyl radicals and by compound I of peroxidases or catalase.

Since 3-hydroxyanthranilic acid (3HAA), an oxidation product of tryptophan metabolism, is a powerful radical scavenger [Christen, S., Peterhans, E., & Stocker, R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2506], its reaction with peroxyl radicals was investigated further. Exposure to aqueous peroxyl radicals generated at constant rate under air from the thermolabile radical initiator 2,2'-azobis[2-amid-inopropane] hydrochloride (AAPH) resulted in rapid consumption of 3HAA with initial accumulation of its cyclic dimer, cinnabarinic acid (CA). The initial rate of formation of the phenoxazinone CA accounted for approximately 75% of the initial rate of oxidation of 3HAA, taking into account that 2 mol of 3HAA are required to form 1 mol of CA. Consumption of 3HAA under anaerobic conditions (where alkyl radicals are produced from AAPH) was considerably slower and did not result in detectable formation of CA. Addition of superoxide dismutase enhanced autoxidation of 3HAA as well as the initial rates of peroxyl radical-induced oxidation of 3HAA and formation of CA by approximately 40-50%, whereas inclusion of xanthine/xanthine oxidase decreased the rate of oxidation of 3HAA by approximately 50% and inhibited formation of CA almost completely, suggesting that superoxide anion radical (O2.-) was formed and reacted with reaction intermediate(s) to curtail formation of CA. Formation of CA was also observed when 3HAA was added to performed compound I of horseradish peroxidase (HRPO) or catalytic amounts of either HRPO, myeloperoxidase, or bovine liver catalase together with glucose/glucose oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyanthranilic Acid↗

PubMed1992

Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation.

Ubiquinol-10 (CoQH2, the reduced form of coenzyme Q10) is a potent antioxidant present in human low-density lipoprotein (LDL). Supplementation of humans with ubiquinone-10 (CoQ, the oxidized coenzyme) increased the concentrations of CoQH2 in plasma and in all of its lipoproteins. Intake of a single oral dose of 100 or 200 mg CoQ increased the total plasma coenzyme content by 80 or 150%, respectively, within 6 h. Long-term supplementation (three times 100 mg CoQ/day) resulted in 4-fold enrichment of CoQH2 in plasma and LDL with the latter containing 2.8 CoQH2 molecules per LDL particle (on day 11). Approx. 80% of the coenzyme was present as CoQH2 and the CoQH2/CoQ ratio was unaffected by supplementation, indicating that the redox state of coenzyme Q10 is tightly controlled in the blood. Oxidation of LDL containing various [CoQH2] by a mild, steady flux of aqueous peroxyl radicals resulted immediately in very slow formation of lipid hydroperoxides. However, in each case the rate of lipid oxidation increased markedly with the disappearance of 80-90% CoQH2. Moreover, the cumulative radical dose required to reach this 'break point' in lipid oxidation was proportional to the amount of CoQH2 incorporated in vivo into the LDL. Thus, oral supplementation with CoQ increases CoQH2 in the plasma and all lipoproteins thereby increasing the resistance of LDL to radical oxidation.

Adult↗