Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix

Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n = 30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system.     

Erythrocyte Lipid Peroxidation and Antioxidants in Gastric Cancer Patients

The present study has analysed the relationship between lipid peroxidation and antioxidant status in erythrocytes from 24 adult male gastic cancer patients and an equal number of age- and sex-matched normal subjects. Erythrocyte lipid peroxidation was markedly increased. Both enzymic and non-enzymic antioxidants were decreased in erythrocytes of gastric cancer patients. The present study highlights the occurrence of lipid peroxidation and possible breakdown of antioxidant status in patients with gastric carcinoma. © 1997 John Wiley & Sons, Ltd.     

Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer

Free radicals participate in the development of cancer. When the antioxidant defence system is not longer capable to destroy free radicals they may cause lipid and protein oxidation. Lipid peroxidation products also modify proteins. In such a situation the proteolytic-antiproteolytic balance existing in the blood may be changed. Therefore the aim of this study was to examine the correlation between antioxidant status and activity of proteolytic enzymes and their inhibitors in cases of colorectal cancer. This study included 55 patients with colorectal cancer. The blood was taken before surgery and plasma was collected. Total antioxidant status, the levels of lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) and activity of cathepsin G, elastase and their inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were determined in plasma. It was shown that during the development of cancer total antioxidant status was signficantly decreased while lipid peroxidation products were increased. Activity of alpha-2-macroglobulin was decreased and activity of determined enzymes was not significantly changed. The observed changes indicate a shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis.     

Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium

Oxidative stress is considered to be involved in pathogenesis of many disorders of the female genital tract. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of uterine diseases in order to evaluate the extent of oxidative stress in blood of such patients. Blood samples of healthy subjects and gynecological patients were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides. The results show that alterations of measured parameters vary with the enzyme type and diagnosis. However, both reduction in antioxidants and elevation of lipid peroxidation were observed in general. Lipid hydroperoxides level was negatively correlated to superoxide dismutase and glutathione peroxidase activities, as well as positively correlated to catalase activity. In addition, the lipid hydroperoxides/ glutathione peroxidase ratio was found to be increased, according to the type of uterine disease. The obtained results show that perturbation of antioxidant status is more pronounced in blood of patients with premalignant (hyperplastic) and malignant (adenocarcinoma) lesions, compared to those with benign uterine changes such as polypus and myoma.     

Changes observed in antioxidant system in the blood of postmenopausal women with breast cancer.

From experimental studies and epidemiological data, it can be inferred that lipid peroxidation is increased in cancer patients. Cases of post-menopausal, untreated women with benign and malignant breast tumours, were compared with their age matched controls in their serum lipid peroxides, antioxidant vitamins (E and C), serum selenium and serum ceruloplasmin. Erythrocyte and its membrane lipid peroxidation and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase) levels were also analyzed. Significant increase in circulating lipid peroxides, ceruloplasmin and significant decrease in antioxidant vitamins and selenium were observed in breast cancer women. The erythrocyte and its membrane lipid peroxidation was increased significantly and severe impairment of antioxidant potential was observed in breast cancer women.     

A rapid prognostic electrophoretic assay for serum lipid conjugates in carcinoma uterine cervix and breast

The levels of cholesterol and lipid associated sialic acid in sera of patients with carcinoma uterine cervix and breast cancer were determined using agarose electrophoresis and precipitation method. Elevated level of lipid associated sialic acid was found, that was specifically reflected only in LDL and VLDL fractions. In carcinoma uterine cervix patients, cholesterol in low density lipoprotein increased with corresponding decrease in high density lipoprotein and there was no change in total as well as VLDL cholesterol content. But breast cancer patients were found to have higher concentrations of both total and high density lipoprotein cholesterol. A good positive correlation was found between electrophoresis and precipitation methods for the lipoprotein analysis. We recommend electrophoretic method for rapid routine analysis.     

Evaluation of Oxidative Stress, Antioxidant Status and Serum Vitamin C Levels in Cancer Patients

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19–80 years and 22 healthy subjects (control group) aged 22–76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.     

Altered lipid peroxidation and antioxidant potential in human uterine tumors.

A comparative study of lipid peroxidation and antioxidant potential has been made in human uterus and uterine tumor. Two types of uterine tumor used are: tumor (I), a fibroid which is the commonest benign solid tumor in uterus and tumor (II), an adenomyoma. Tumor microsomes are less susceptible to lipid peroxidation induced by both enzymic (NADPH-ADP-Fe3+ and xanthine-xanthine-oxidase) and non-enzymic (ascorbate-Fe2+) systems except in the case of tumor (II) microsomes when induced with xanthine-xanthine oxidase. Resistance of tumor microsomes to lipid peroxidation is associated with the low content of substrates in the form of polyunsaturated fatty acids (PUFAs), higher level of alpha-tocopherol, reduced glutathione and protein thiols and altered enzymic antioxidant potential (catalase and superoxide dismutase).     

Antioxidant properties of rimantadine in influenza virus infected mice and in some model systems

Influenza virus infection is associated with development of oxidative stress in lung and blood plasma, viz. increase of primary and secondary lipid peroxidation products. It was established that rimantadine treatment led to a decrease of the products of lipid peroxidation in tissues of mice experimentally infected with influenza virus A/Aichi/2/68 (H3N2). The effect is strongest in blood plasma (a decrease of about 50%) and weaker in the lung (about 20%). To elucidate the mechanism of this action of rimantadine, experiments were carried out with some model systems. The capability of rimantadine to scavenge superoxide radicals (scavenging properties) was studied in a system of xanthine-xanthine oxidase to generate superoxide. The amount of superoxide was measured spectrophotometrically by the NBT-test and chemiluminesce. Rimantadine does not show scavenging properties and its antioxidant effect observed in vivo, is not a result of its direct action on the processes of lipid peroxidation and/or interaction with antioxidant enzymes. The antioxidant properties of rimantadine were investigated by measurement of induced lipid peroxidation in a Fe2+ and (Fe2+ - EDTA) system with an egg liposomal suspension. Our findings with model systems do not prove an antioxidant or prooxidant effect of the drug on the processes of lipid peroxidation. Apparently, the observed antioxidant effect of rimantadine in vivo is not connected directly with free radical processes in the organism.     

Synergistic interactions of Ferulic acid with Ascorbic acid: Its cardioprotective role during isoproterenol induced myocardial infarction in rats

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.     

Modulatory effect of Piperine on mitochondrial antioxidant system in Benzo(a)pyrene-induced experimental lung carcinogenesis.

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Many bioactive compounds present in edible as well in herbal plants have revealed their cancer chemopreventive potential. In the present study, our goal was to investigate the impact of piperine, a principle ingredient of pepper, on alterations of mitochondrial antioxidant system and lipid peroxidation in Benzo(a)pyrene (B(a)P) induced experimental lung carcinogenesis. Oral supplementation of piperine (50 mg/kg body weight) effectively suppressed lung carcinogenesis in B(a)p induced mice as revealed by the decrease in the extent of mitochondrial lipid peroxidation and concomitant increase in the activities of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and non enzymatic antioxidant (reduced glutathione, vitamin E and vitamin C) levels when compared to lung carcinogenesis bearing animals. Our data suggests that piperine may extent its chemopreventive effect by modulating lipid peroxidation and augmenting antioxidant defense system.     

Rat liver antioxidant defense mechanism to the action of aromatic amines]

The effects of diaminobiphenyl, biphenylamine and tetraaminobiphenyl on lipid peroxidation and antioxidant protective mechanisms in the subcellular fractions of rat liver have been studied. It was found that activation of lipid peroxidation plays a crucial role in the manifestation of hepatotoxic activities of diaminobiphenyl and biphenylamine, this effect being due to the decrease of the protective activity of the antioxidant system during intoxication by these compounds. Tetraaminobiphenyl does not influence the rate of lipid peroxidation. It is concluded that structural differences determine the differences in the mechanisms of adaptation of the antioxidant system to the effect of aromatic amines.     

Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in isoproterenol-induced myocardial infarction. The present study was designed to evaluate the effect of alpha-mangostin on the antioxidant defense system and lipid peroxidation against isoproterenol-induced myocardial infarction in rats. Induction of rats with ISO (150 mg/kg body weight, ip) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT) and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GST, and GSH). Pre-treatment with alpha-mangostin (200 mg/kg of body weight per day) orally for 6 days prior to the ISO administration and 2 days along with ISO administration significantly attenuated these changes when compared to the individual treatment groups. These findings indicate the protective effect of alpha-mangostin on lipid peroxidation and antioxidant tissue defense system during ISO-induced myocardial infarction in rats.     

Saliva plays a dual role in oxidation process in stomach medium

The aim of this study was to evaluate the role of saliva in the oxidation process under the acidic condition of the stomach. Saliva specimens played varied roles in the lipid peroxidation process of heated muscle tissue in simulated gastric fluid: pro-oxidant effects, no effects, and antioxidant effects. To elucidate these differences, selected saliva components were examined. The pseudoperoxidase activity of lactoperoxidase increased lipid peroxidation, while thiocyanate and nitrite-reduced lipid peroxidation. The effect of a saliva specimen on lipid peroxidation was correlated with the concentration of nitrite in the specimen, but not with that of other saliva components. The inhibitory effect of nitrite may be due to its conversion to NO. Elucidation of the antioxidant effect of saliva on co-oxidation of d-alpha-tocopherol in gastric fluid, demonstrated that saliva alone cannot protect d-alpha-tocopherol from co-oxidation, although it partially protected against lipid peroxidation. The presence of red wine polyphenols in stomach medium totally inhibits food lipid peroxidation and d-alpha-tocopherol co-oxidation.     

Effects of 5-Fluorouracil on Oxidative Stress and Calcium Levels in the Blood of Patients with Newly Diagnosed Colorectal Cancer

The administration of chemotherapeutic agents for colorectal carcinoma is associated with an increase in oxidative stress and a concomitant decrease in antioxidant and element levels in the blood. This study investigated the effects of 5-fluorouracil (5-FU) chemotherapy on the levels of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), antioxidant vitamins, and elements in colorectal cancer patients. Twelve patients with newly diagnosed colorectal carcinoma and 12 healthy subjects were included in this study. Blood samples were collected from both the healthy controls and patients. 5-FU was intravenously administered to the patients for 6 weeks, and blood samples were collected again from the treatment group. In the patient group, lipid peroxidation levels were increased in both the plasma and erythrocyte samples, whereas GSH-Px activity and concentrations of GSH, vitamin E, and β-carotene in erythrocytes were decreased. The oxidant, antioxidant, and plasma calcium values were lower in 5-FU-treated patients than in the controls. Plasma vitamin A, chloride, sodium, and potassium concentrations did not change with 5-FU treatment. In conclusion, oxidative stress in patients with newly diagnosed colorectal cancer is attributable to the disease and not to 5-FU treatment. Blood vitamin E, β-carotene, GSH, and GSH-Px levels could be useful as early biomarkers of the prognosis of colorectal cancer patients.     

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.     

Lipid antioxidant properties of quercetin in vitro

The effect of quercetin on iron-catalyzed hepatic microsomal lipid peroxidation was investigated. Quercetin was shown to be a potent inhibitor of iron-induced lipid peroxidation with a I50 of 0.2 mM. The inhibitory effects of quercetin were dependent on incubation time, protein concentration and iron content in the incubation mixture. Since quercetin does not interact with malonyl-aldehyde it can be concluded that the inhibition of iron induced lipid peroxidation is due to lipid antioxidant property and this may serve as a model for the study by which "free" iron may initiate peroxidation in vivo.     

Effects of ethanol and limontar in the antenatal period of development on lipid peroxidation process and antioxidant defense system in the brain and liver tissue of fetal and newborn rats]

The process of lipid peroxidation and the system of antioxidant defense in brain and liver of fetuses on the 20th day of gestation and 1 day old rats after antenatal exposure to ethanol and limontar were studied. It was shown that antenatal exposure to ethanol led to activation of the process of lipid peroxidation in brain and to inhibition of of the enzyme system of antioxidant defense in liver of fetal and newborn rats. Limontar promoted the normalization of both the process of lipid peroxidation and the system of antioxidant defense.     

The antioxidant status during maturation of reticulocytes to erythrocytes in type 2 diabetics

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. The extent of lipid peroxidation (LPO) and antioxidant defense system [i.e., levels of glutathione (GSH), glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and catalase (CAT)] were evaluated in reticulocytes and erythrocytes of type 2 diabetic males and age-matched controls. Type 2 diabetics have shown increased lipid peroxidation and decreased levels of GSH, GR, GPx, G6PDH, and GST both in reticulocytes and erythrocytes compared to controls, indicating the presence of oxidative stress and defective antioxidant systems in these patients. CAT activity is found to be enhanced in both the reticulocytes and erythrocytes of diabetics, with a greater percentage enhancement in reticulocytes. The extent of increase in lipid peroxidation is greater in erythrocytes compared to reticulocytes in these patients. Furthermore, the maturation of reticulocytes to erythrocytes resulted in decreased GSH and decreased activities of all antioxidant enzymes (except CAT) both in normals and type 2 diabetes individuals, indicating decreased scavenging capacity as reticulocytes mature to erythrocytes. These maturational alterations are further intensified in type 2 diabetics. The present study reveals that the alterations in lipid peroxidation and antioxidant system lean toward early senescence of erythrocytes in type 2 diabetic patients.     

Oxidative stress markers during a course of hyperthyroidism

INTRODUCTION: Previous studies have shown the presence of oxidative stress in hyperthyroid patients. The aim of this study was to evaluate the influence of hyperthyroidism on lipid peroxidation, plasma lipoprotein oxidation and antioxidant status. We have estimated the clinical utility of the biochemical parameters analysed as markers of oxidative stress in hyperthyroidism. MATERIAL AND METHODS: Twenty five patients with overt hyperthyroidism because of Graves' disease or toxic multinodular goitre and 20 healthy subjects were included in the study. Lipid peroxidation was evaluated by measurement of peroxides and malondialdehyde with 4-hydroxynonenal (MDA + 4-HNE) concentrations. Autoantibodies against oxidised LDL (anti-oxLDL) were assayed as a marker of lipoprotein oxidation. Changes in the antioxidant defence system were estimated by measurement of total antioxidant status in serum (TAS) and erythrocyte superoxide dismutase activity (SOD). RESULTS: A significant increase in serum concentration of peroxides and MDA + 4-HNE was observed in patients with hyperthyroidism. However, no difference was found in anti-oxLDL concentration and antioxidant status parameters (TAS, SOD) between the control group and the patient group. CONCLUSIONS: Our results indicate an intensification of the oxidative processes caused by an excess of thyroid hormones, which is not accompanied by a response from the antioxidant system. Elevated concentrations of lipid peroxidation products in serum, both peroxides and malondialdehyde with 4-hydroxynonenal, may be useful as markers of oxidative stress during the course of hyperthyroidism.