Serum contains various antioxidant molecules that may provide important protection against free radical attack. The aim of this work was to assess the total antioxidant capacity of plasma and a marker of lipid per oxidation [(thiobarbituric acid-reactive substances (TBARS)] in plasma of healthy smoking and non-smoking young and elderly subjects. In addition, we investigated plasma concentrations of α-tocopherol, β-carotene, and ascorbic acid. In in vitro experiments, the effects of exogenous compounds (ascorbic acid, uric acid, Trolox) on total ferric-reducing activity of plasma (FRAP) were also tested. We demonstrated that total antioxidant capacity of plasma obtained from healthy non-smoking young subjects was significantly higher than plasma antioxidant capacity of smoking elderly subjects. The concentration of TBARS in young non-smoking volunteers was lower than that in young smokers. The concentration of TBARS in elderly non-smoking volunteers was lower than in elderly smokers. Plasma concentrations of alpha-tocopherol, beta-carotene and ascorbic acid were significantly lower in elderly smoker than in elderly non-smokers of the same age. No difference in the plasma levels of alpha-tocopherol, beta-carotene and ascorbic acid were found in 22-year-old smoking and non-smoking subjects. In vitro addition of ascorbic acid, uric acid, or Trolox to plasma samples significantly increased their total antioxidant capacity. Decrease of FRAP values and increase of TBARS concentrations is a significant physiologic condition of the aging process. Supplementation of antioxidants could be useful for the enhancement of antioxidant screen in plasma.
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In the present study, we evaluated the plasma concentration of inflammatory mediators including cytokines and their relation with oxidative damage markers in training cycles of basketball players.Sixteen professional players of the Polish Basketball Extraleague participated in the study. The basketball players were observed during the preparatory period and the play-off round. Twenty healthy and untrained males composed of the reference group.The comparative study has shown significantly higher levels of lipid peroxidation (TBARS) and protein carbonylation (PC) in nonathletes than in basketball players during the observed training periods. Tumour necrosis factor α (TNFα), similarly to TBARS and PC, was significantly higher in nonathletes than athletes, except at the end of the play-off round. Interleukin-6 (IL-6) was lower in nonathletes than athletes in the preparatory period but it was higher in athletes in play-off round. In basketball players, the high level of IL-6 directly correlated with TBARS (r = 0.763, p<0.001) and PC (r = 0.636, p<0.001) during the preparatory period, whereas the high level of TNF α inversely correlated with TBARS (r = −0.601, p<0.001) and PC (r = −0.650, p<0.001) in the play-off round. The activity of creatine kinase (CK) was significantly increased during the training mezocycles in basketball players compared with nonathletes, and reached the highest activity at the end of the play-off round. CK activity did not correlate with oxidative damage markers and cytokines in both untrained and trained subjects.Our results have shown the reduction in oxidative damage and improvement in cytokine response following professional training, as well as the relationship between inflammatory and pro-oxidative processes in basketball players.
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Paraoxonase 1 (PON1), contained in plasma high-density lipoproteins, plays an important role in the protection of plasma lipoproteins and cell membranes from oxidative damage. Previous studies indicate that human PON1 is stimulated by high NaCl concentrations. The aim of this study was to characterize in more detail the effect of salts on serum PON1. Paraoxon-hydrolyzing activity of human serum was stimulated by 81.6% following the addition of 1 M NaCl. The effect of NaCl was dose-dependent between 0.5 and 2 M. PON1 activity toward phenyl acetate was reduced by 1 M NaCl by 55.2%. Both the paraoxon- and phenyl acetate-hydrolysing activity was slightly lower in heparinized plasma than in serum, but NaCl had similar stimulatory and inhibitory effects on these activities, respectively. In rat, rabbit, and mouse, NaCl reduced PON1 activity. KCl had a similar effect on human PON1 as NaCl. Sodium nitrite also stimulated human PON1 but much less effectively than chloride salts. In contrast, sucrose, sodium acetate and sodium lactate had no significant effect. NaBr was a less effective PON1 activator than NaCl, whereas the effect of NaJ was non-significant. The activity of human PON1 toward homogentisic acid lactone and γ-decanolactone was unaltered by NaCl. These data indicate that: 1) high concentrations of chlorides stimulate human PON1 activity toward paraoxon but not other substrates, 2) PON1 is inhibited by Cl- in other mammalian species, 3) the potency of human PON1 activation by halogene salts increases with decreasing atomic mass of the halide anion.
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Oxygen is one of the most important molecules on Earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet's biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. They can be considered a double-edged sword because at moderate concentrations, nitric oxide (NO•), superoxide anion, and related reactive oxygen species play an important role as regulatory mediators in signalling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and re-establish "redox homeostasis". On the other hand, overproduction of ROS has the potential to cause damage. In the recent decades, ROS has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases shows that oxidative stress is associated with the pathogenesis of diabetes mellitus, obesity, cancer, cardiovascular diseases, inflammation, ischaemia/reperfusion injury, obstructive sleep apnea, neurodegenerative disorders, hypertension and ageing.
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Particles generated from numerous anthropogenic and/or natural sources, such as crystalline α-Fe2O3 nanoparticles, have the potential to damage lung cells. In our study we investigated the effects of these nanoparticles (12.5 µg/ml) on lipid peroxidation and the antioxidative system in MRC-5 lung fibroblast cells following exposure for 24, 48 or 72h. Exposure to α-Fe2O3 nanoparticles increased lipid peroxidation by 81%, 189% and 110% after 24, 48 and 72h, respectively. Conversely, the reduced glutathione concentration decreased by 23.2% and 51.4% after 48 and 72h of treatment, respectively. In addition, an augmentation of the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase within the interval between 48-72h was noticed. Taking into account that the reduced glutathione level decreased and the malondialdehyde level, a lipid peroxidation product, remained highly increased up to 72h of exposure, it would appear that the MRC-5 antioxidant defense mechanisms did not efficiently counteract the oxidative stress induced by exposure to hematite nanoparticles.
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To analyze the effects of conventional polychemotherapy of acute myeloblastic leukemia (AML) patients on the prooxidants/antioxidants balance in plasma total antioxidant status (TAS) and a single plasma antioxidant - uric acid (UA) were measured. Lipid peroxidation was assessed by malonedialdehyde (MDA) content. Total serum iron was monitored as a potential source of nontransferrin-bound iron with a role in initiation of oxidative burst. A group of patients in the acute phase of AML (group A) and a group of patients in complete remission of AML (group B) were studied. A strong correlation between UA values and TAS (r = 0.8 for group A, r = 0.9 for group B) was revealed in the course of the treatment. Strong negative correlation (r = −0.9) between TAS and MDA was shown for both groups. Total iron significantly increased in the course of chemotherapy. We have established that polychemotherapy leads to the consumption of antioxidants and increased lipid peroxidation in AML patients. An appropriate supplementation with antioxidants at the end of the polychemotherapy treatment could be considered.
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The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS), arginase, cyclooxygenase (COX) and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs) synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX) inhibitor, darbufelone) were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS). WRS brought about an increase of inducible NOS (iNOS) activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS) and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.
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Bone regeneration is a process of vital importance since fractures of long bones and large joints have a highly deleterious impact on both, individuals and society. Numerous attempts have been undertaken to alleviate this severe medical and social problem by development of novel bioactive materials, among which bioactive glass is the most attractive because of its osteoconductive and osteostimulative properties. Since lipid peroxidation is an important component of systematic stress response in patients with traumatic brain injuries and bone fractures, studies have been undertaken of the molecular mechanisms of the involvement of 4-hydroxynonenal (HNE), an end product of lipid peroxidation, in cellular growth regulation. We found that HNE generated in bone cells grown in vitro on the surfaces of bioactive glasses 45S5 and 13-93. This raises an interesting possibility of combined action of HNE and ionic bioglass dissolution products in enhanced osteogenesis probably through a mitogen-activated protein kinase (MAPK) pathway. While the proposed mechanism still has to be elucidated, the finding of HNE generation on bioglass offers a new interpretation of the osteoinducting mechanisms of bioglass and suggests the possibility of tissue engineering based on manipulations of oxidative homeostasis.
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The present study was designed to evaluate the oxidative stress-related parameters in alloxan-induced diabetes in rabbits. After 3, 6, 12 and 24 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in heart tissue of diabetic and control groups. Superoxide dismutase and glutathione peroxidase activities and the contents of total sulfhydryl compounds significantly increased at all time intervals. Catalase activity increased initially (after 3 and 6 weeks), decreased after 12 weeks and increased again at the 24th week of the experiment. Glutathione reductase activity increased initially (at 3rd week), decreased below control level after 6 and 12 weeks, then increased again. Ascorbic acid concentration decreased after 3 and 6 weeks, and increased at the 12th and 24th weeks. The level of lipid peroxidation products was reduced after 3, 6 and 12 weeks of the experiment. After 24 weeks it was significantly elevated. These data suggest that hyperglycaemia induces oxidative stress in the heart but the defense mechanisms in the heart tissue are fairly efficacious against oxidative injury.
Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5-60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (ironmediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis.
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Oxidative stress enhances lipid peroxidation (LPO) implicated in cancer promotion and progression. (E)-4-Hydroxynon-2-enal 1 (trans-4-hydroxy-2-nonenal, HNE) is one of the most abundant products of LPO. Reactions of HNE with DNA and proteins are responsible for its mutagenic and toxic effects. On the other hand, HNE is regarded as a key molecule in stress mediated cell cycle signaling. LPO generates racemic HNE (rac-1); however, it is expected that the individual enantiomers will behave differently in their interactions with cell components. The study of HNE stereochemistry in its chemical and biochemical interactions is hindered by the lack of expedient methods for preparation of pure enantiomers. This study presents one step synthesis of HNE in a cross-metathesis reaction between the commercially available oct-1-en-3-ol and acrolein in the presence of 2nd generation Grubbs catalyst. The use in the metathesis reaction of enantiomers of oct-1-en-3-ol obtained via Candida antarctica lipase resolution of the racemate allowed us to prepare of 4-(R)- and 4-(S)-enantiomers of HNE (R-1 and S-1, respectively) with excellent optical purity (97.5 and 98.4% ee, respectively) and good chemical yields (70%).
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In this work was investigated the effect of pre-treatment with (PhSe)2 and (PhTe)2 on chemical seizure and 4-aminopyridine-induced lethality in mice. Additionally, lipid peroxidation levels of whole brain after treatment with 4-aminopyridine and effect of pre-treatment with (PhSe)2 and (PhTe)2 on these levels were investigated. Mice were pre-treated with (PhSe)2 or (PhTe)2 (50, 100, or 150 µmol/kg) 30 min before 4-aminopyridine (12 mg/kg) administration. The treatment with 4-aminopyridine caused a significant incidence of seizures (clonic, tonic) and death. Pre-treatment with (PhSe)2 and (PhTe)2 significantly increased the latency for clonic and tonic seizures, and prevented 4-aminopyridine-induced death. Significantly, the pre-treatment with (PhSe)2 or (PhTe)2 increased the latency for clonic seizures in a dose-dependent manner. Additionally, a significant increase was observed in the brain lipid peroxidation level after treatment with 4-aminopyridine, which was significantly inhibited by pre-treatment with 150 µmol/kg (PhSe)2 or (PhTe)2. These results demonstrate that (PhSe)2 and (PhTe)2 counteract the harmful effects of 4-aminopyridine. It is possible that this effect results from modulation of the redox state of N-methyl-d-aspartate receptors and/or of Ca2+ channel activity with subsequent alteration in neurotransmitter release. Importantly, this study provides evidence for anticonvulsant and antioxidant properties of (PhSe)2 and (PhTe)2, which indicates a neuroprotective activity of these compounds.
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Infrared (IR)-A irradiation can be useful in back and musculoskeletal pain therapy. In this study joint and vertebral column pain and mobility were measured during two weeks of IR-A irradiation treatment of patients suffering from degenerative osteoarthritis of hip and knee, low back pain, or rheumatoid arthritis. Additionally, before and after IR-A treatment MDA serum levels were measured to check if MDA variations accompany changes in pain intensity and mobility. Two-hundred and seven patients were divided into verum groups getting IR-irradiation, placebo groups getting visible, but not IR irradiation, and groups getting no irradiation. In osteoarthritis significant pain reduction according to Visual Analogue Scale and mobility improvements occurred in the verum group. Even though beneficial mean value changes occurred in the placebo group, the improvements in the placebo and No Irradiation groups were without statistical significance. In low back pain, pain and mobility improvements (by 35-40%) in the verum group were found, too. A delayed (2nd week) mobility improvement in rheumatoid arthritis was seen. However, pain relief was seen immediately. In patients suffering from low back pain or rheumatoid arthritis, the pain and mobility improvements were accompanied by significant changes of MDA serum levels. However, MDA appears not a sensitive biofactor for changes of the pain intensity in degenerative osteoarthritis. Nevertheless, unaffected or lowered MDA levels during intensive IR-A therapy argue against previous reports on free radical formation upon infrared. In conclusion, rapid beneficial effects of IR-A towards musculoskeletal pain and joint mobility loss were demonstrated.
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Natural and synthetic derivatives of benzo-γ-pyrones (i.e. flavones, chromones, and coumarins) and their synthetic analogues possess a wide range of biological properties in vitro and in vivo. In this paper we investigated the influence of two hydrazone compounds of chromones, 3-{[(2-dimethoxytiophosphoryl)-2-methylhydrazono]-methyl}-chromen-4-one (CH-3) and 2-amino-6-chloro-3-[(2-hydroxyethyl)-hydrazonomethyl]-chromen-4-one (A-12), on lipid peroxidation and bFGF concentration in the HL-60 cells. Both of the studied compounds had a significant influence on bFGF and TBARS in ranges -137.20 ~ 380.26% and -81.66 ~ -28.68%, respectively, in comparison with the control (counted as 0 %).
BACKGROUND Free radical processes are known to induce oxidative damage in biomolecules and thus, play an important role in the etiology of a number of diseases including cancer. Phytic acid (myo-inositol hexaphosphate, IP6) is a naturally occurring carbohydrate widely found in fi ber-rich foods and also contained in almost all mammalian cells. This compound demonstrates various biological activities. The aim of this study was to clarify whether phytic acid possesses the ability to inhibit autooxidation and Fe(II)/ascorbate-induced peroxidation of linoleic acid, to scavenge of hydrogen peroxide, and chelate ferrous ions. MATERIAL AND METHODS The antioxidant properties of the IP6 at various concentrations (1-500 μM) have been evaluated by using the assays based on hydrogen peroxide scavenging and ferrous metal ions chelating activity determination. The eff ect of IP6 (1-500 μM) on autooxidation and Fe(II)/ascorbate-induced lipid peroxidation in micelles of linoleic acid after 24 h incubation was investigated using a reverse-phase high-performance liquid chromatography (RP-HPLC) with UV detection. RESULTS The Fe(II) chelating eff ects of IP6 were concentration-dependent. IP6 exhibited 11,9%, 58,6%, 69,3%, 87,1% of ferrous ions chelation at 10 μM, 50 μM, 100 μM, 500 μ , respectively. IP6 at 100 μM and 500 μM eff ectively inhibited the disappearance of linoleic acid, both in the absence and the presence of Fe(II)/ascorbate. The inhibitory eff ect of IP6 on Fe(II)/ascorbate-induced lipid peroxidation was lower due to its direct interaction with Fe(II) ions. In the absence of Fe(II)/ascorbate, IP6 at 100 μM and 500 μM signifi cantly suppressed decomposition of linoleic acid hydroperoxides. It was incapable of scavenging of hydrogen peroxide. Conclusions: IP6 can act as a natural antioxidant in vitro. The obtained results suggest that it can play an important role in modulating lipid hydroperoxide level in biological systems.
PL
WSTĘP Procesy wolnorodnikowe, prowadzące do oksydacyjnych uszkodzeń biomolekuł, pełnią ważną rolę w etiologii licznych schorzeń, włączając choroby nowotworowe. Kwas fi tynowy (sześciofosforan mio-inozytolu, IP6) jest naturalnie rozpowszechnionym węglowodanem występującym obfi cie w diecie o dużej zawartości włókna pokarmowego, jak również obecnym w prawie wszystkich komórkach ssaków. Związek ten wykazuje szerokie spektrum działania biologicznego. Celem pracy było zbadanie, czy kwas fi tynowy posiada zdolność do hamowania autooksydacji i peroksydacji kwasu linolowego indukowanej jonami Fe(II) w obecności kwasu askorbinowego oraz czy jest zdolny do unieszkodliwiania nadtlenku wodoru i chelatowania jonów Fe(II). MATERIAŁ I METODY Do zbadania antyoksydacyjnych właściwości IP6 w wybranych stężeniach (1-500 μM) zastosowano metody pozwalające ocenić stopień zmiatania nadtlenku wodoru oraz aktywność chelatującą jony Fe(II). Wpływ IP6 (1-500 μM) na autooksydację oraz indukowaną jonami Fe(II) w obecności kwasu askorbinowego peroksydację w micelach kwasu linolowego po 24 godzinach inkubacji określano stosując wysokosprawną chromatografi ę cieczową w odwróconym układzie faz (RP-HPLC) i detekcję UV. WYNIKI IP6 w sposób zależny od stężenia chelatował jony Fe(II). Procent schelatowanych jonów Fe(II) wynosił 11,9%, 58,6%, 69,3%, 87,1% odpowiednio dla stężeń IP6 10 μM, 50 μM, 100 μM, 500 μM. IP6 w stężeniach 100 μM i 500 μM znacząco hamował zanik kwasu linolowego zarówno w nieobecności i obecności układu redoks Fe(II)/kwas askorbinowy. Hamujący wpływ IP6 na indukowaną przez Fe(II)/kwas askorbinowy peroksydację był mniejszy, ze względu na bezpośrednią interakcję IP6 z Fe(II). W nieobecności układu redoks Fe(II)/kwas askorbinowy, IP6 w stężeniach 100 μM i 500 μM, znacznie hamował rozpad wodoronadtlenków kwasu linolowego. IP6 nie był zdolny do zmiatania nadtlenku wodoru. Wnioski: IP6 może działać jako naturalny antyoksydant w warunkach in vitro. Wyniki badań sugerują, że może on pełnić istotną rolę w modulowaniu poziomu wodoronadtlenków lipidowych w układach biologicznych.
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Two natural flavonoids, quercetin and isorhamnetin 3-O-acylglucosides, were examined for their inhibitory influence on the in vitro production and release of reactive oxygen species in polymorphonuclear neutrophils (PMNs). The generation of superoxide radical, hydrogen peroxide and hypochlorous acid were measured by, respectively, cytochrome c reduction, dichlorofluorescin oxidation and taurine chlorination. Membrane lipid oxidation was studied by the thiobarbituric acid method in mouse spleen microsomes. The addition of flavonoids at the concentration range 1-100 μM inhibited PMNs oxidative metabolism and lipid peroxidation in a dose-dependent manner. The results suggest that these flavonoids suppress the oxidative burst of PMNs and protect membranes against lipid peroxidation.
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The objective of this study was to assess the dynamics of oxidative damage to cellular macromolecules such as proteins, lipids and DNA under conditions of oxidative stress triggering early stages of estrogen-dependent carcinogenesis. A rodent model of carcinogenesis was used. Syrian hamsters were sacrificed after 1, 3, 5 h and one month from the initial implantation of estradiol. Matching control groups were used. Kidneys as target organs for estradiol-mediated oxidative stress were excised and homogenized for biochemical assays. Subcellular fractions were isolated. Carbonyl groups (as a marker of protein oxidation) and lipid hydroxyperoxides were assessed. DNA was isolated and 8-oxodGuo was assessed. Electron paramagnetic resonance spectroscopy was used to confirm the results for lipid peroxidation. Exposition to estradiol in the rodent model leads to damage of macromolecules of the cell, including proteins and DNA, but not lipids. Proteins appear to be the primary target of the damage but are closely followed by DNA. It has previously been speculated that protein peroxides can increase DNA modifications. This time sequence was observed in our study. Nevertheless, the direct relation between protein and DNA damage still remains unsolved.
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Unsaturated lipids are rapidly oxidized to toxic products such as lipid hydroperoxides, especially when transition metals such as iron or copper are present. In a Fenton-type reaction Fe2+ converts lipid hydroperoxides to the very short-lived lipid alkoxyl radicals. The reaction was started upon the addition of Fe2+ to an aqueous linoleic acid hydroperoxide (LOOH) emulsion and the spin trap in the absence of oxygen. Even when high concentrations of spin traps were added to the incubation mixture, only secondary radical adducts were detected, probably due to the rapid rearrangement of the primary alkoxyl radicals. With the commercially available nitroso spin trap MNP we observed a slightly immobilized ESR spectrum with only one hydrogen splitting, indicating the trapping of a methinyl fragment of a lipid radical. With DMPO or 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) adducts were detected with carbon-centered lipid radical, with acyl radical, and with the hydroxyl radical. We also synthesized lipophilic derivatives of the spin trap DEPMPO in order to detect lipid radical species generated in the lipid phase. With all spin traps studied a lipid-derived carbon-centered radical was obtained in the anaerobic incubation system Fe2+/LOOH indicating the trapping of a lipid radical, possibly generated as a secondary reaction product of the primary lipid alkoxyl radical formed. Under aerobic conditions an SOD-insensitive oxygen-centered radical adduct was formed with DEPMPO and its lipophilic derivatives. The observed ESR parameters were similar to those of alkoxyl radical adducts, which were independently synthesized in model experiments using Fe3+-catalyzed nucleophilic addition of methanol or t-butanol to the respective spin trap.
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Myeloperoxidase (MPO), an abundant enzyme in phagocytes, has been implicated in the pathogenesis of various inflammatory diseases including atherosclerosis. The major oxidant produced by MPO, hypochlorous acid (HOCl), is able to modify a great variety of biomolecules by chlorination and/or oxidation. In this paper the reactions of lipids (preferentially unsaturated fatty acids and cholesterol) with either reagent HOCl or HOCl generated by the MPO-hydrogen peroxide-chloride system are reviewed. One of the major issues has been whether the reaction of HOCl with lipids of low density lipoprotein (LDL) yields predominantly chlorohydrins or lipid hydroperoxides. Electrospray mass spectrometry provided direct evidence that chlorohydrins rather than peroxides are the major products of HOCl- or MPO-treated LDL phosphatidylcholines. Nevertheless lipid peroxidation is a possible alternative reaction of HOCl with polyunsaturated fatty acids if an additional radical source such as pre-formed lipid hydroperoxides is available. In phospholipids carrying a primary amino group such as phosphatidylethanolamine chloramines are the preferred products compared to chlorohydrins. Cholesterol can be converted by HOCl to great variety of oxysterols besides three isomers of chlorohydrins. For the situation in vivo it appears that the type of reaction occurring between HOCl and lipids would very much depend on the circumstances, e.g. the pH and the presence of radical initiators. The biological effects of lipid chlorohydrins are not yet well understood. It has been shown that chlorohydrins of both unsaturated fatty acids as well as of cholesterol may cause lysis of target cells, possibly by disruption of membrane structures.
Quetiapine, a second generation antipsychotic, has no significant effect on the occurrence of tardive dyskinesia or other motoric disorders whose aetiology may be related to a pro- and antioxidative imbalance. The mechanism of quetiapine effect on the oxidative stress biomarkers remains unknown. The aim of the study was to establishthe effect of quetiapine, administered in doses recommended in the treatment of acute phase of schizophrenia, on lipid peroxidation measured by levels of thiobarbituric acid reactive substances (TBARS) and on free thiols in human plasma in vitro. Material and methods: Blood samples were obtained from 10 healthy volunteers – males and females aged 24–26 (mean 25, SD = 0.6) and placed in the ACD solution. Quetiapine was dissolved in a 0.01% solution of dimethylsulfoxide to reach the final concentration of 400 ng/ml and incubated with plasma for 24 h at 37°C. For each experiment a control test (without drug) has been done. Thiol levels were evaluated by the Ellmann method and the TBARS concentrations by the spectrophotometric Rice-Evans method. For statistical analysis we used the t-test (Statistica 6.0, StatSoft, Inc.). Results: Quetiapine at 400 ng/ml shows antioxidative properties causing an increase of plasma free thiol level and decrease of plasma lipid peroxidation.
PL
Kwetiapina, lek przeciwpsychotyczny drugiej generacji, nie wywiera istotnego wpływu na występowanie późnej dyskinezy oraz innych zaburzeń ruchowych (movement disorders), w których etiopatogenezę mogą być zaangażowane zaburzenia równowagi pro- i antyoksydacyjnej. Mechanizm działania kwetiapiny na biomarkery stresu oksydacyjnego, a tym samym na redoks, nie jest znany. Celem badania było ustalenie wpływu kwetiapiny, w dawkach rekomendowanych do leczenia ostrego epizodu schizofrenii, na peroksydację lipidów mierzoną za pomocą oznaczenia stężenia związków reagujących z kwasem tiobarbiturowym (TBARS) oraz na wolne tiole w ludzkim osoczu, w modelu in vitro. Materiał i metody: Krew do badań pobrano od 10 zdrowych ochotników – kobiet i mężczyzn w wieku 24–26 lat (średnio 25 lat, SD = 0,6 roku) – na roztwór ACD. Substancję aktywną kwetiapiny rozpuszczono w 0,01% dimetylosulfotlenku do stężenia końcowego 400 ng/ml i inkubowano z osoczem przez 24 godziny w temperaturze 37°C. Do każdego doświadczenia wykonano próby kontrolne (bez leku). Oznaczenia poziomu wolnych tioli przeprowadzono metodą Ellmana, a stężenia TBARS – metodą spektrofotometryczną opisaną przez Rice’a-Evansa. Do analizy wyników zastosowano sparowany test t-Studenta (StatSoft Inc., Statistica v. 6.0). Wyniki: Stwierdzono, że kwetiapina w stężeniu 400 ng/ml w porównaniu z próbami kontrolnymi powoduje istotny statystycznie spadek stężenia TBARS o 22% (p < 0,04) oraz wywiera istotny wpływ na wzrost stężenia wolnych tioli (p < 0,002). Wniosek: Kwetiapina w stężeniu 400 ng/ml wykazuje działanie antyoksydacyjne, powodując wzrost stężenia wolnych tioli w osoczu i zmniejszenie peroksydacji lipidów osocza.
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