Vitamin E supplementation, exercise and lipid peroxidation in human participants

The theoretical benefits of using antioxidant vitamin supplements to quench oxygen free radicals appear large. The major function of vitamin E is to work as a chain-breaking antioxidant in a fat soluble environment so as to protect polyunsaturated fatty acids within membrane phospholipids and in plasma lipoproteins. The purpose of this critical review was to determine whether vitamin E supplementation decreases exercise-induced lipid peroxidation in humans. If vitamin E alone is ineffective, researchers can turn their efforts to other individual antioxidants or combinations. Using the search words vitamin E, exercise, lipid peroxidation and antioxidant, all relevant studies since 1985 were identified through a computer search using Pub Med and Sport Discuss databases. Additional articles were reviewed from the reference list of the retrieved articles. Nine vitamin E studies met the criteria of using human participants in an experimental design. Studies were analyzed to determine the strength of evidence regarding the efficacy of vitamin E supplementation. Strength of evidence was based on: (1) number of participants, (2) intensity of the exercise test, (3) type of research design, (4) other controls, (5) the biomarker of lipid peroxidation, (6) the timing of the biomarker measurement, (7) measurement of vitamin E status and (8) correction for plasma volume change. Overall, the six studies showing no effect of vitamin E supplementation had a much higher total score (67) in comparison to the three studies showing positive effects (38). Although limitations have plagued much of the research, vitamin E supplementation does not appear to decrease exercise-induced lipid peroxidation in humans.     

Effects on antioxidant status of liver following atrazine exposure and its attenuation by vitamin E

In the present investigation, the effect of atrazine on antioxidant enzymes and body weight was studied in male Wistar rats. Atrazine (300 mg/kg bw) was administered by gavage for 7, 14 and 21 days. A significant increase in hepatic lipid peroxidation (LPO) was observed following atrazine administration. Vitamin E treatment (100 mg/kg bw), on the otherhand, attenuated atrazine-induced LPO in liver. In addition, vitamin E treatment restored the GSH content and glucose-6-phosophate dehydrogenase activity that was found to be lowered after atrazine administration. The activities of antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase were significantly increased following atrazine administration and vitamin E treatment could restore these activities. In conclusion, the results of the study demonstrate that atrazine induces oxidative stress in terms of enhanced lipid peroxidation. However, vitamin E treatment ameliorated the effects of atrazine suggesting it as potential antioxidant against atrazine-induced oxidative stress.     

Acute bout of exercise does not alter the antioxidant enzyme status and lipid peroxidation of rat hippocampus and cerebellum

It is known that acute strenuous physical exercise may cause diverse pathophysiological consequences in various organs, due to exercise-induced increase in free radical formation. The effect of acute exercise on brain antioxidant system and lipid peroxidation is still unknown. We report here that an acute bout of exercise, which results in several-fold increase of plasma xanthine oxidase activity, does not alter significantly the antioxidant enzyme status of hippocampus and cerebellum, and does not induce lipid peroxidation in those brain regions.     

Influence of polychemotherapy on the antioxidant levels and lipid peroxidation in patients with lymphoproliferative diseases

The purpose of the present study was to compare the oxidative stress parameters such as the extent of lipid peroxidation and the status of antioxidants in patients with lymphoproliferative diseases. The effect of polychemotherapy on the level of lipid peroxidation products and on the activities of antioxidant defense enzymes was also investigated. Lipid peroxidation (malondialdehyde or MDA), superoxide dismutase (SOD), catalase (CAT), and ceruloplasmin (CER) activities, were measured in 58 patients with non-Hodgkins lymphoma, Hodgkins disease, chronic lymphocytic leukemia, and acute lymphoblastic leukemia before treatment, during and after polychemotherapy. Plasma levels of MDA and CER in plasma were increased in comparison with the control group before any treatment. Erythrocyte SOD activity was significantly lower but CAT activity was significantly higher in patients than those in controls. Moreover, the levels of MDA and CER increased by the effect of the different regimens of polychemotherapy, which appeared to be compromised by augmented activity of antioxidant enzymes SOD and CAT. The levels of plasma MDA were found to be significantly higher in comparison to the control group for patients treated with cyclophosphamide, vincristine, prednisolon (CVP) and adriamicine, bleomicine, vinblastine, dacarbasine (ABVD), (p<0.01). Erythrocyte SOD statistically decreased (p<0.001) and CAT activities statistically increased in patients treated with CVP and ABVD (p<0.001). In conclusion, our results suggest that after polychemotherapy, the oxidative stress and the imbalance of antioxidant enzyme systems significantly progresses in patients with lymphoproliferative hematological diseases. Patients treated with CVP and ABVD are at the biggest risk of oxidative injury. Thus, the antioxidant status of cancer patients may play an important role in their response to chemotherapy.     

Lipid peroxidation in the postnatal rat brain

Lipid peroxidation is known to be associated with many neurodegenerative diseases and with traumatic brain injury, but its occurrence in the normal developing brain has not been reported. The present study was carried out using a specific antibody that recognises proteins modified by the end-product of lipid peroxide decomposition, 4-hydroxynonenal (HNE), to evaluate evaluate possible lipid peroxidation products in the brains of developing rats by immunocytochemistry and electron microscopy. Moderately dense labelling was observed in the supraventricular corpus callosum in the 7- and 8-day-old rats, whilst very dense labelling was observed in the same region, in the 9- and 10-day-old rats. Very little immunoreactivity was observed at 14 days, and no staining was observed in the corpus callosum in adult rats. HNE staining was not observed in neuronal cell bodies that give rise to callosal axons in the overlying cerebral cortex. Electron microscopy showed dense HNE staining on the basal laminae of blood vessels and on the plasma membranes of unmyelinated axons. Large numbers of rounded cells with features of oligodendrocyte precursor cells were labelled by Perl's stain in the supraventricular corpus callosum at postnatal day 7 and postnatal day 10, i.e. at times corresponding to high levels of HNE immunoreactivity. In contrast, very few such cells were observed in the adult brain, corresponding to the very little or no Perl's staining in the adult. These results suggest that lipid peroxidation observed in the supraventricular corpus callosum at postnatal day 10 could result from an accumulation of iron in this region, at this time.     

The evaluation of effects of lipoic acid on the lipid peroxidation,nitrite formation and antioxidant enzymes in the hippocampus of rats after pilocarpine-induced seizures

It has been suggested that pilocarpine-induced seizures is mediated by increases in oxidative stress. Current researches have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the neuroprotective effects of lipoic acid (LA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 6 h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA were also evaluated on the same parameters. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite level. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the superoxide dismutase and catalase activities in hippocampus of rats after seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that strong protective effect could be achieved using lipoic acid as an antioxidant.     

Influence of oxygen tension, pro-oxidants and antioxidants on the formation of lipid peroxidation products (lipofuscin) in individual cultivated human glial cells

Cultivated human glial cells, kept in a state of density-dependent inhibition of growth, accumulate age pigment (lipofuscin) within their lysosomal vacuomes which has the same characteristics as the age pigment observed in vivo. The rate of formation and accumulation of lipofuscin is greatly accelerated under the conditions of routine cell culture in comparison to the in vivo event. Lipofuscin is generally considered to be composed of products of lipid peroxidation and thus it would be reasonable to suggest that factors which influence lipid peroxidation would also alter the rate of lipofuscin formation and accumulation. Human glial cells were grown in the presence of various oxygen concentrations (5%, 10%, 20%, 40%) or exposed to pro-oxidants (vitamin C/Fe) or antioxidants (vitamin E/Se, dimethylsulfoxide, reduced glutathione) treatments in the presence of normal oxygen concentration (20%). It was found that these factors can modulate (accelerate or decrease) the rate of formation of lipofuscin. This study thus provides: (1) important supportive evidence for the lipid peroxidation origin of lipofuscin, (2) a useful model system for studying the effect of lipofuscin accumulation on lysosomal function and cell growth kinetics, (3) evidence that our culture conditions are far from ideal: oxygen concentration may drastically alter rates of lipofuscin formation and accumulation. Cell culture technique, as we know it today, may benefit from more closely controlled oxygen tensions, i.e. by reducing oxygen to levels that more closely approximate conditions in vivo.     

大鼠烧伤后血清过氧化脂质含量的变化

用80℃水烫伤大鼠腰部以下身体30秒(占体表面积35—40%)引起烧伤休克。在烧伤后不同时间取血测定血中脂质过氧化物的二级产物丙二醛的含量。烧伤后1、2小时的血中脂质过氧化物含量已开始上升,3.5小时明显增高,5小时达高峰,7小时开始下降,但仍明显高于正常。在高峰出现前(烧伤后4.5小时)开始用平衡克氏液腹腔透析治疗,透析1.5小时可以使增多的血清脂质过氧化物恢复到接近正常。血中脂质过氧化物出现的时间经过与动物烧伤休克的发展过程基本一致,提示自由基使脂质过氧化带来组织损伤可能参与烧伤休克的发生。腹腔透析的疗效进一步阐明该疗法治疗烧伤休克的原理。     

家兔多器官衰竭发病过程中脂质过氧化损伤及维生素E对其影响

本文利用家兔MOF模型观察了血中MDA、SOD、Se—GSH、CAT的含量变化及应用Vit E后对其影响。结果MOF动物血中MDA含量随着MOF的发生发展呈逐渐上升趋势,其72h值(48.2±5.9nmol/ml)与实验前(2.7±0.1)及对照组(3.1±0.4)比均具有非常显著差异(P<0.01);而此时SOD含量呈逐渐降低趋势,72h值(231.1±1.077μg/gHb)与实验前比(589.4±4.4)与对照组比(569.8±23.4)也有非常显著差异。同时其他抗氧化酶含量也发生不同情况的变化。当补充Vit E后前述各项指标均得到不同程度的改善。观察提示MOF时体内抗氧化能力明显降低,脂质过氧化损伤明显增强。这种平衡失调可能在MOF发病过程中具有重要病理生理意义;早期应用Vit E对防治MOF有益。     

Decrease of the inhibition of lipid peroxidation by glutathione-dependent system in erythrocytes of non-insulin dependent diabetics

Summary The inhibition of lipid peroxidation of erythrocyte membranes by glutathione-dependent protection was studied in patients with non-insulin dependent diabetes mellitus. Incubation of red cells from diabetics with 1.5 mM t-butyl hydroperoxide resulted in a lipid peroxidation increase greater than that of normal controls. Glutathione-dependent and glutathione-independent protection against oxidative damage was examined using an artificial system, in which erythrocyte ghosts were incubated with t-butyl peroxide and dialysed hemolysate in the presence or the absence of 2 mM glutathione. The glutathione-dependent protection of hemolysate from diabetics was approximately 70% of that from normal controls.The results suggest that decrease in glutathione-dependent protection against lipid peroxidation, along with decrease in glutathione levels, increases oxidative damage in erythrocyte membranes taken from diabetic patients.Abbreviations GSH reduced form of glutathione - GSSG glutathione disulfide - TCA trichloracetic acid - SOD superoxide dismutase - GPX glutathione peroxidase - MDA malondialdehyde     

Xanthine oxidase activity and lipid peroxide content following different types of ischemia in the isolated rat heart

It is currently believed that reactive oxygen species are produced in the heart post-ischemia-reperfusion, causing pathophysiological disorders. Studies reported in the literature dealing with this subject have generated contradictory findings. The aim of this study was to assess the catalytic activity of the superoxide anion-producing enzyme xanthine oxidase, and the level of lipid peroxides in isolated rat heart muscle undergoing ischemia of varying duration and severity followed by reperfusion.Three levels of ischemia were investigated: total, and partial at either 0.10 or 0.35 ml/min (residual flow rate). Three different periods of ischemia were examined in each case. After each period of ischemia, followed by 10 min of reperfusion, the heart was frozen in liquid nitrogen. Xanthine oxidase activity and lipid peroxide levels were assayed in the cardiac homogenate and in the centrifuged supernatant, respectively. In the different experimental protocols studied here, both cardiac xanthine oxidase and lipid peroxide levels remained statistically unchanged compared to the continuously perfused control hearts. Moreover, in a recent study (Boucher et al., FEBS Lett. 203, 261–264, 1992), we were unable to detect reactive oxygen species in perfusate upon reperfusion of ischemic rat hearts.These results suggest that changes in xanthine oxidase activity during myocardial ischemia-reperfusion, and lipid peroxidation, as assessed by measuring thiobarbituric acid reactants and lipid hydroperoxides, are not predominant phenomena in ischemia-reperfusion-induced injury, at least in the experimental model used in this study. The significance of these results is discussed in the light of the popular point of view suggested first by McCord in 1985 concerning the conversion of xanthine dehydrogenase to xanthine oxidase in heart in the course of ischemia.     

自由基诱发剂对大肠癌细胞脂质过氧化、膜脂流动性及DNA含量的影响

本文以体外培养的大肠癌细胞为模型，观察了自由基诱发剂ｔｂｏｏＨ及抗癌药物对癌细胞脂质过氧化、膜脂流动性及ＤＮＡ含量的影响。结果表明，作用早期ＬＰＯ含量即有明显增加，且随温育时间的延长而增强，但早期ＤＮＡ含量则无明显变化，提示细胞ＬＰＯ含量的变化出现于细胞核酸ＤＮＡ改变之前。ｔｂｏｏＨ结合５－ＦＵ作用于癌细胞，发现在早期ＤＮＡ便可出现抑制作用，提示细胞膜的脂质过氧化损伤可增强抗癌药物的作用。采用ＤＰＨ荧光探针标记观察了细胞脂质过氧化与膜脂流动性的关系，结果表明ｔｂｏｏＨ和５－ＦＵ均能不同程度地引起大肠癌细胞膜脂流动性的减少。且这一效果可因抗癌药５－ＦＵ并用ｔｂｏｏＨ而明显增强，提示细胞膜膜脂流动性的改变是脂质过氧化介导癌细胞功能障碍的重要机制。     

Changes in the antioxidant state and intensity of lipid peroxidation in the blood and liver during 30-day hypokinesia

Thirty-day hypokinesia was accompanied by an increase in plasma antioxidant activity and inactivation of liver antioxidant enzymes. The observed activation of blood antioxidant enzymes during hypokinesia was associated with increased resistance to acute hypoxic hypoxia.     

家兔内毒素性DIC时血清LPO含量、红细胞SOD活力的变化及意义

本实验用内毒素复制家兔DIC模型,以硫代巴比妥酸法测定血清LPO含量,以邻苯三酚法测定红细胞SOD活力,探讨二者变化及自由基反应在内毒素性DIC病理过程中的意义。结果表明:模型组血清LPO含量(9.36±2.65)与对照组(6.62±1.91)比较明显增高(P<0.01),而红细胞SOD活力(1676.41±374.01)与对照组(2225.66±411.85)比较明显降低(P<0.005)。提示自由基可能参与了DIC的病理过程并且是致组织损伤的重要因素之一。本文对该病理过程中自由基增多可能的机制进行了讨论。     

Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia

Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO₂) and carbon dioxide (PCO₂) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions,PO₂ was significantly lower in the subendocardium (13.5±4.5 mm Hg) than in the subepicardium (20.7±2.3 mm Hg), whereasPCO₂ did not differ significantly (43±8.8 and 51±9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardialPO₂ decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardialPO₂ was 4.1±6.3 mm Hg while subepicardialPO₂ was 6.7±15.0 mm Hg (P<0.05).PCO₂ reached peak values of 56±25 mm Hg subendocardial and 82±22 mm Hg subepicardial at 2.67±0.71 min and 3.43±0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows whilePO₂ recovered with different kinetics. SubendocardialPO₂ increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium.     

Vitamin C antioxidant effects in hippocampus of adult Wistar rats after seizures and status epilepticus induced by pilocarpine

Vitamin C (VIT C) is an exogenous antioxidant able to alter the brain oxidative stress. Antioxidant properties have been showed in seizures and status epilepticus (SE) induced by pilocarpine in adult rats. This present study was aimed at was investigating the VIT C effects on latency to first seizure, in percentage of seizures, mortality rate, as well as hippocampal lipid peroxidation levels and catalase activity after seizures and SE. The VIT C effects were investigated after the pretreatment with dose 250mg/kg, i.p., 30min before pilocarpine administration (400mg/kg, s.c., pilocarpine group (P400)). The VIT C increase the latency to first seizure and decrease the mortality rate and lipid peroxidation levels. In P400+VIT C and VIT C groups were observed an increase in hippocampal catalase activity. Our results suggests that the vitamin C can exert antioxidant and anticonvulsive effects in adult rats, suggesting that this vitamin can be able by reduction of lipid peroxidation content and increased of catalase enzymatic activity which cerebral compensatory mechanisms in free radical formation during SE.     

Transmural gradients of glycolytic enzyme activities in left ventricular myocardium

Summary Twelve experiments were performed on healthy, anesthetized dogs on constant ventilation. Blood pressure, acid-base status, oxygen supply and lactate/pyruvate metabolism were monitored in the blood. The activities of nine glycolytic enzymes were assayed in left ventricular myocardium. A presumably irreversible state of hemorrhagic shock was produced by the reservoir technique and its metabolic sequels recorded in the blood. The analysis of coronary sinus blood did not reveal an oxygen deficit of the heart. The majority of the enzymes assayed showed higher activities following shock. Exceptions were pyruvate kinase, LDH and -HB-DH. Activity differences between sampling sites appeared following shock especially in the inner layer of the left ventricle. The pattern of transmural activity gradients previously found in the normal state was disturbed. The findings are against an oxygen deficit as a cause of cardiac deterioration in shock, suggesting structural derangements possibly due to catecholamine effects or toxic substances of peripheral origin.Work supported by Research Grant No. 4139 from the Swiss National Foundation for the Advancement of Scientific Research.     

Effect of age on oxygen consumption,superoxide dismutase,catalase, glutathione,inorganic peroxides and chloroform-soluble antioxidants in the adult male housefly, Musca domestica

The objective of this study was to determine whether aging in the housefly is associated with a general decline in the efficiency of the mechanisms protective against the intermediates of oxygen metabolism. The rate of oxygen consumption, activities of superoxide dismutase (total and cyanide-insensitive) and catalase, and levels of inorganic peroxides, glutathione (GSH and GSSG) and chloroform-soluble antioxidants were measured in adult male houseflies at different ages. Rate of oxygen consumption declined in flies approaching the average life span of the population. Activity of total and cyanide-insensitive superoxide dimutase decreased during the last trimester of life. Catalase activity steadily declined with age while the concentration of inorganic peroxides gradually increased during the later two-thirds of the average life span. Levels of total glutathione and GSH decreased during later half of life whereas the relative concentration of GSSG increased during this period. The concentration of chloroform-soluble antioxidants sharply declined during the first half of life. These results are interpreted to suggest that the enzymatic and non-enzymatic defenses against oxygen free radicals and hydroperoxides tend to deteriorate with age in the adult housefly.