Lipid peroxidation products,and vitamin and trace element status in patients with cancer before and after chemotherapy,including adriamycin

Adriamycin is a potent chemotherapeutic agent used in the treatment of human neoplastic diseases. A major side effect limiting the use of this drug is its toxic effect on the heart. Several hypotheses have been proposed to explain the cardiotoxicity of Adriamycin. However, the most plausible hypothesis seems to be the reduction of Adriamycin and free radical production, which induces lipid peroxidation and oxidative damages in the heart. We have thus undertaken this preliminary study to investigate Adriamycin-induced lipid peroxidation by the measurement of plasma thiobarbituric acid reactant materials and antioxidant systems, namely glutathione content, glutathione peroxidase activity, and vitamin and trace element status, in patients with cancer before and after chemotherapy, including Adriamycin. The concentration of thiobarbituric acid reactant materials in plasma of patients with cancer was higher than in controls and was further increased after chemotherapy. Blood glutathione and plasma glutathione peroxidase activity, as well as plasma zinc and selenium in patients with cancer, were decreased, but not further modified by chemotherapy. However, only zinc and selenium levels reached a significant level. In contrast, plasma vitamin E and β-carotene levels were not significantly increased in patients with cancer. Finally, plasma vitamin A and copper levels were not modified either in patients with cancer or by chemotherapy.     

Antioxidant status and lipid peroxidation in athymic mice xenografted with two types of human tumors

Antioxidants and reactive oxygen species are considered to play an important role in experimental in vivo carcinogenesis studies. We attempted in this study to evaluate the repercussions on the antioxidant and lipid peroxide status of the growth of human malignant tumors xenografted into athymic mice. We selected three tumor models: two urothelial carcinomas (bladder tumors stage 3) and one brain tumor (glioblastoma stage 4). All these tumors exhibited a fast growth pattern when xenografted into athymic mice. Tumoral tissue was implanted subcutaneously. After growth establishment each tumor size was measured at regular intervals: every 2 d for bladder tumor and twice a week for glioblastoma. The period of observation was 3 wk for bladder tumors and 5 wk for glioblastoma. At the end of the observation period, all mice were sacrificed; tumoral tissue was taken and blood collected. Superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px), zinc (Zn), selenium (Se), and thiobarbituric acid reactive substances (TBARS) were measured in blood. TBARS alone were measured into tumoral tissue. A modification of the antioxidant blood status was observed in mice xenografted with bladder tumors with decrease in Se status and GSH-Px activities, and increase in TBARS. Such an effect was absent in mice xenografted with glioblastoma. It would appear that an oxygen-mediated stress exists in the animal bearing an implanted tumor compared with the control group, and that tumoral tissue itself is able to induce an oxidative stress into its host. All this leads to a disturbance of the antioxidant defense system.     

Effects of acute manganese chloride exposure on lipid peroxidation and alteration of trace metals in rat brain

Although manganese (Mn) is an essential element, exposure to excessive levels of Mn and its accumulation in the brain can cause neurotoxicity and extrapyramidal syndrome. We have investigated the differences in the accumulated levels of Mn, the degree of lipid peroxidation, and its effects on the levels of trace elements (Fe, Cu, and Zn) in various regions in the brain of rats having undergone acute Mn exposure. The rats in the dose—effect group were injected intraperitoneally (ip) with MnCl₂ (25, 50, or 100 mg MnCl₂/kg) once a day for 24 h. The Mn significantly accumulated (p<0.05) in the frontal cortex, corpus callosum, hippocampus, striatum, hypothalamus medulla, cerebellum, and spinal cord in each case. The rats in the timecourse group were ip injected with MnCl₂ (50 mg MnCl₂/kg) and then monitored 12, 24, 48, and 72 h after exposure. The Mn accumulated in the frontal cortex, corpus callosum, hippocampus, striatum hypothalamus, medulla, cerebellum, and spinal cord after these periods of time, In both the dose—effect and time-course studies, we observed that the concentration of malondialdehyde, an end product of lipid peroxidation, increased significantly in the frontal cortex, hippocampus, striatum, hypothalamus, medulla, and cerebellum. However, no relationship between the concentrations of Mn in the brain and the extent of lipid peroxidation was observed. In addition, we found that there was a significant increase (p<0.05) in the level of Fe in the hippocampus, striatum, hypothalamus, medulla, and cerebellum, but the Cu and Zn levels had not changed significantly. These findings indicated that Mn induces an increase in the iron level, which provides direct evidence for Fe-mediated lipid peroxidation in the rats' brains; these phenomena might play important roles in the mechanisms of Mn-induced neurotoxicology.     

Trace element profiles in cancer patients

It has become evident over the last two decades that there is an intimate relationship between the trace elements and cancer. Some trace elements have been shown to be carcinogens, others appear to provide protection against cancer. Profound changes in trace element concentrations and distribution occur in patients with cancer, but most changes remain undefined. A review of a number of studies of trace element changes in patients with cancer demonstrates that simple correlations of trace element levels in disease are of only limited use. Such reports underscore the need for large-scale studies that consider the many variables of malignancies and of trace element chemistry. The variables that must be considered for cancer include tissue of origin; histologic, pathologic and clinical staging; nutritional status as reflected by serum levels of calcium, iron, magnesium, phosphorus, the electrolytes, pH, albumen, and globulin; endocrine balance, effects of previous and concurrent therapies such as surgery, chemotherapy, hormonal manipulation, immunotherapy, and radiotherapy; history of exposure to toxic agents; and the presence of other disease. Similarly, trace element studies entail variables that must be considered and controlled prospectively, including timing and techniques of sampling, storage, and analysis, and simultaneous measurement of at least the majority of possibly interrelated elements rather than studying one element at a time. The various national cooperative oncology groups such as ECOG, SWOG, and SEOG now offer unusually well-studied groups of cancer patients who are managed according to carefully and prospectively defined protocols in participating institutions. With present knowledge, it is now time to approach these groups with a proposal to incorporate trace element studies in their protocols. A potential protocol will be discussed.     

Nonesterified fatty acids and lipid peroxidation

Oxygen free radicals damage cells through peroxidation of membrane lipids. Gastrointestinal mucosal membranes were found to be resistant to in vitro lipid peroxidation as judged by malonaldehyde and conjugated diene production and arachidonic acid depletion. The factor responsible for this in this membrane was isolated and chemically characterised as the nonesterified fatty acids (NEFA), specifically monounsaturated fatty acid, oleic acid. Authentic fatty acids when tested in vitro using liver microsomes showed similar inhibition. The possible mechanism by which NEFA inhibit peroxidation is through iron chelation and iron-fatty acid complex is incapable of inducing peroxidation. Free radicals generated independent of iron was found to induce peroxidaton of mucosal membranes. Gastrointestinal mucosal membranes were found to contain unusually large amount of NEFA. Circulating albumin is known to contain NEFA which was found to inhibit iron induced peroxidation whereas fatty acid free albumin did not have any effect. Addition of individual fatty acids to this albumin restored its inhibitory capacity among which monounsaturated fatty acids were more effective. These studies have shown that iron induced lipid peroxidation damage is prevented by the presence of nonesterified fatty acids.     

Trace elements in coal

Trace elements can have profound adverse effects on the health of people burning coal in homes or living near coal deposits, coal mines, and coal-burning power plants. Trace elements such as arsenic emitted from coal-burning power plants in Europe and Asia have been shown to cause severe health problems. Perhaps the most widespread health problems are caused by domestic coal combustion in developing countries where millions of people suffer from fluorosis and thousands from arsenism. Better knowledge of coal quality characteristics may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals in coal may help to predict the behavior of the potentially toxic trace metals during coal cleaning, combustion, weathering, and leaching.     

Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis

In recent years, a great number of studies have investigated the possible role of reactive oxygen species in the aetiology and pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate plasma concentrations of vitamin E, beta-carotene, activities of glutathione peroxidase (GSH-Px) and catalase, levels of lipid peroxidation (MDA) and reduced glutathione (GSH) in 36 patients with rheumatoid arthritis (RA) and 22 healthy age-matched controls. The plasma activity of GSH-Px and catalase (p < 0.001), levels of GSH (p < 0.01), concentration of beta-carotene (p < 0.05) and vitamin E (p < 0.001), haemoglobin and hematocrit (p < 0.05) were significantly lower in patients with RA than in controls. The MDA levels (p < 0.01), C reactive protein, rheumatoid factor, anti-streptolysin-o values (p < 0.001), platelet count (p < 0.05) and erythrocyte sedimentation rate (p < 0.001) were higher in the patient group than in the control group. These results provide some evidence for a potential role of increased lipid peroxidation and decreased enzymic and non-enzymic antioxidants in RA by its inflammatory character. These results suggested that oxidant stress plays a very important role in the pathogenesis of RA.     

Effects of magnesium and iron on lipid peroxidation in cultured hepatocytes

In primary cultures of rat hepatocytes, the effects of extracellular Mg²⁺ and Fe on lipid peroxidation (LPO) as measured by means of malondialdehyde (MDA) formation were investigated.Incubation of hepatocytes at decreasing extracellular Mg²⁺ concentration enhanced LPO, depending on extracellular Fe. About 96% of MDA accumulated in the culture medium. Addition of desferrioxamine prevented LPO.Additionally, the formation of oxygen free radicals was determined by fluorescence reduction of cis-parinaric acid. With this method, an immediate decay of fluorescence was found after addition of Fe²⁺. Fluorescence reduction was completely prevented by desferrioxamine, indicating the function of extracellular Fe. This mechanism may operate additionally to the increase in intracellular Fe and intracellular formation of oxygen free radicals during Mg deficiencyin vivo.     

Plasma and erythrocyte lipid peroxidation levels in patients with testis tumor after orchiectomy

Plasma and erythrocyte lipid peroxidation levels of 20 patients with histopathologically confirmed testis cancer and 20 healthy control individuals were studied between November 1995 and June 1997. The group with testis cancer had a mean age of 24.8±8.2 yr and the control group’s mean age was 28.3±6.9 yr. Stage distribution of the testis cancer cases were 4 of stage A, 10 of stage B, and 6 of stage C. Blood samples of the patients were drawn after orchiectomy and after 12 h fasting before chemotherapy. Mean plasma and erythrocyte lipid peroxidation levels were detected to be 14.51±5.30 nmol malondialdehide (MDA)/mL and 9.30±2.06 nmol MDA/g hemoglobin (Hb), respectively, in the testis cancer group, whereas the healthy control group had mean plasma and erythrocyte lipid peroxidation levels of 10.7±1.82 nmol MDA/mL and 6.18±1.68 nmol MDA/g Hb, respectively. Plasma and erythrocyte lipid peroxidation values of the testis cancer patients were determined to be statistically significantly higher than that of the health control group (p<0.001, p<0.001). No significant correlation was determined between plasma, erythrocyte lipid peroxidation levels and tumor markers. In conclusion, it can be said that an increase in the lipid peroxidation may play a role in the pathogenesis of testis carcinomas in addition to the other causes.     

GA1处理采后油桃果实膜脂过氧化的影响

采后GA3处理“阿姆肯”油桃果实（Prunus Persica (L.)nectarine.cv.‘armking’),降低了果实中过氧化氢（H2O2）积累和膜脂过氧化产物丙二醛（MDA）含量,显著提高了活性氧清除酶过氧化氢酶（CAT）和抗氧化剂谷胱甘肽（GSH）的含量,降低了果实衰老期间的膜脂过氧化,对“阿姆肯”油桃有一定保鲜效果。     

Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation

Adriamycin (25 μM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin-enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron.     

Cadmium induced lipid peroxidation in rat testes and protection by selenium

The main goal of this study was to investigate the role of cadmium in the promotion of lipid peroxidation in the homogenates of rat testes and the effect of selenium on lipid peroxidation in testes of rats after cadmium injection. Treatment of rats with cadmium resulted in a time- and dose-related accumulation of the metal ions in testes. The concentrations of cadmium, copper, zinc, selenium and iron in the tissues were determined by an atomic absorption spectrophotometer and lipid peroxidation in testes was measured by a spectrophotometer. Cadmium produced enhanced lipid peroxidation in testes. These cadmium-induced changes were accompanied by a significant increase of iron and copper, and a decrease of zinc in testes. Concurrent treatment with selenium and cadmium reduced the cadmium-induced alterations in lipid peroxidation and essential metal levels. Data suggest that lipid peroxidation was associated with cadmium toxicity in testes and that the addition of selenium was found to be effective in attenuation of this effect.     

镍对水稻离体叶片脂质过氧化作用的影响

杂交水稻离体叶片用１０－３ｍｏｌ／ＬＮｉＳＯ４处理后,镍阻抑了叶片在衰老过程中ＳＯＤ、ＣＡＴ酶活性的下降和ＡｓＡ氧化酶活性的上升,ＡｓＡ和叶绿素含量的下降得到延缓,减少了膜脂过氧化程度。     

Effects of zinc on copper-induced and spontaneous lipid peroxidation

Zinc (Zn) is an essential nonredox metal that has been regarded as having antioxidant properties. Some epidemiological indications and therapeutic results point to a role of Zn in restricting the development and the progression of some diseases. Redox-active metals like iron and copper are involved in oxidative injury mechanisms, and a decrease in the Zn∶Cu ratio may be associated with certain pathologies. We studied the effect of Zn on the copper-induced lipid peroxidation in diluted human plasma. Lipid peroxidation was evaluated by measuring the formation of conjugated dienes and of thiobarbituric acid reactive products. We found that 20 μM Zn reduced the 125-μM copper-dependent formation of conjugated dienes by 27% and of thiobarbituric acid reactive products by 49%, during a 3-h incubation period. The inhibition of lipid peroxidation by 125 μM Zn is almost total in the same conditions. The time-course study of the inhibitory effect of 125 μM Zn showed that it lasted for 7 h, which was the maximum incubation period tested. We also found that Zn had an inhibitory effect on the spontaneous lipid peroxidation in rat brain whole homogenates. Our results support the antioxidant properties of Zn, which may be potentially relevant to the protection of human plasma constituents, competing with the transition metals for redox reactions.     

Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages

Oxidative stress is considered to be implicated in the pathophysiology of breast cancers. In this study we investigated the level of oxidative stress and antioxidant (AO) status in the blood of breast cancer patients of different ages. The level of lipid hydroperoxides (LP) was measured in blood plasma and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) enzymes, as well as the level of total glutathione (GSH) and CuZnSOD protein were measured in blood cells of breast cancer patients and age-matched healthy subjects. Our results showed that breast carcinoma is related to increase of lipid peroxidation in plasma with concomitant decrease of AO defense capacity in blood cells, which becomes more pronounced during aging of the patients. Suppression of CuZnSOD activity related to breast cancer is most likely caused by decreased de novo synthesis of this enzyme. Similar patterns of suppression in CuZnSOD and CAT activities related to aging were recorded both in controls and patients. Age-related decrease in CuZnSOD activity seems not to be caused by altered protein levels of this enzyme. Suppression of AO enzymes associated with breast cancer and aging is most likely the cause of increased levels of reactive oxygen species (ROS). Our results indicate significant role of oxidative-induced injury in the breast carcinogenesis, particularly during the later stages of aging. Overall, our data support the importance of endogenous AOs in the etiology of breast cancer across all levels of predicted risk.     

Effect of vitamin C and zinc on osmotic fragility and lipid peroxidation in zinc-deficient haemodialysis patients

Peroxidation of the membrane lipid structure of red blood cell leads to haemolysis and anaemia in haemodialysis patients. Dietary constituents of antioxidant vitamins and trace elements may play an important role in protecting against oxidant damage. In this study, the effects of supplementation of vitamin C and zinc on osmotic fragility and lipid peroxidation of erythrocytes were investigated in 34 zinc-deficient haemodialysis patients. Sixteen sex- and age-matched normal volunteers acted as controls. Patients were randomized to receive vitamin C (250 mg day(-1)), zinc (20 mg day(-1)) or a placebo treatment for 3 months. The levels of vitamin C, zinc, malondialdehyde (MDA) and osmotic fragility were measured initially and 3 months after supplementation. Mean serum concentration of vitamin C and zinc increased significantly in the groups at the end of the respective study periods. Supplementation with vitamin C and zinc improved osmotic fragility, and decreased the level of MDA in the groups, but some side-effects (i.e. nausea, vomiting, fever, muscle pain, weakness) were observed during the zinc treatment. The results showed that the supplementation of both treatments decreased osmotic fragilty and MDA in zinc-deficient haemodialysis patients. However, vitamin C treatment was found to be safer than zinc supplementation.     

Methamphetamine and lipid peroxidation in the rat retina

BACKGROUND: The use of psychoactive drugs during adolescence and early adult life has increased in the last few decades. It is known that developmental exposure to psychostimulants affects the sensory systems, and the retina has been shown to be a target tissue. This work was conducted to evaluate the pattern of lipid peroxidation in the rat retina following prenatal exposure to methamphetamine (MA). METHODS: Pregnant female Wistar rats were given MA (5 mg/kg of body weight/day; SC, in 0.9% saline) from GD 8 to 22. Offspring were sacrificed at postnatal days (PNDs) 7, 14, and 21. The retinas were homogenized, and both the total antioxidant and superoxide dismutase (SOD) activities were measured by enzymatic-colorimetric methods. The lipid peroxidation byproducts (malondialdehyde [MDA] and MDA-like metabolites) were measured by the thiobarbituric acid test. RESULTS: Total antioxidant levels were lower in the MA group at PND 21 in both males and females. The activity of SOD was higher in PND 7 females from the MA group. MDA levels were higher in the MA group at PND 21 in both genders. CONCLUSIONS: These findings suggest that prenatal-induced MA toxicity in the retina may be related to lipid peroxidation processes and oxidative stress.     

Trace elements and lipid peroxidation in human seminal plasma

In the present study, the concentrations of copper, iron, zinc, and malondialdehyde in human seminal plasma were measured and correlated with the sperm count and motility in human semen. Copper, iron, and zinc were analyzed by atomic absorption spectrometry, whereas malondialdehyde was measured by high-performance liquid chromatography. The malondialdehyde concentrations in asthenospermia and oligoasthenospermia were significantly higher than in normospermia. Copper and iron levels were higher in asthenospermia, whereas the zinc concentrations in both oligospermia and asthenospermia were lower than in normal controls. A negative correlation (r = -0.28, p < 0.05) between the malondialdehyde concentration and sperm motility was observed in the abnormal groups. There was no association among copper, iron, zinc, and malondialdehyde in seminal plasma. We concluded that changes in trace elements may be related to sperm quality and that lipid peroxidation, although it is not promoted in the seminal plasma by copper or iron or ameliorated by zinc, may be involved in the loss of sperm motility.     

Enzymic lipid peroxidation in the microsomal fraction of rat brain

Abstract: An enzymic lipid peroxidation system has been demonstrated in the microsomal fraction of rat brain and the requirements and optimal conditions for assay determined. The involvement of NADPH-cytochrome c reductase was demonstrated in vesicles reconstituted with lipids extracted from the brain microsomal fraction. Further characterization of the system made use of substances shown to inhibit the liver microsomal system. α-Tocopherol was shown to be an effective inhibitor of lipid peroxidation in the brain microsomal system, whereas Na₂SO₃ had no effect, which is indicative that free radical transfer occurs only in the hydrophobic regions. Neither superoxide dismutase nor catalase inhibited lipid peroxidation. The implications of an NADPH-cytochrome c reductase-dependent lipid peroxidation system that is not linked to a drug hydroxylation system and appears to differ from the liver microsomal system in a number of other ways are discussed.     

Increased lipid peroxidation in pregnant women after iron and vitamin C supplementation

Iron overload could promote the generation of free radicals and result in deleterious cellular damages. A physiological increase of oxidative stress has been observed in pregnancy. A routine iron supplement, especially a combined iron and vitamin C supplementation, without biological justifications (low hemoglobin [Hb] and iron stores) could therefore aggravate this oxidative risk. We investigated the effect of a daily combined iron supplementation (100 mg/d as fumarate) and vitamin C (500 mg/d as ascorbate) for the third trimester of pregnancy on lipid peroxidation (plasma TBARS), antioxidant micronutriments (Zn, Se, retinol, vitaminE, (β-carotene) and antioxidant metalloenzymes (RBC Cu-Zn SOD and Se-GPX). The iron-supplemented group (n=27) was compared to a control group (n=27), age and number of pregnancies matched. At delivery, all the women exhibited normal Hb and ferritin values. In the supplemented group, plasma iron level was higher than in the control group (26.90±5.52 mmol/L) and TBARs plasma levels were significantly enhanced (p<0.05) (3.62±0.36 vs 3.01±0.37 mmol/L). No significant changes were observed in plasma trace elements and red blood cell antioxidant metalloenzymes. Furthermore, the α-tocopherol plasma level was lowered in the iron-supplemented groups, suggesting an increased utilization of vitamin E. These data show that pharmalogical doses of iron, associated with high vitamin C intakes, can result in uncontrolled lipid peroxidation. This is predictive of adverse effects for the mother and the fetus. This study illustrates the potential harmful effects of iron supplementation when prescribed only on the assumption of anemia and not on the bases of biological criteria.