An Assessment of Oxidative Damage and Non-Enzymatic Antioxidants Status Alteration in Relation to Disease Progression in Breast Diseases.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydroxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E, and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of the oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by a significant decrease in non-enzymatic antioxidants and TAS concentrations (p < 0.05). 8-OHdG and cell proliferation levels were negatively correlated with non-enzymatic antioxidants, namely, vitamin A, vitamin C, and vitamin E levels and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity among the malignant, the benign, and the controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. In conclusion, our results showed that the characterized biomarkers (i.e., low levels of vitamin A, C and D, and the TAS status; and high levels of 8-OHdG) could be used as a suitable method for detecting subjects with malignant and benign breast diseases.

A novel approach to study oxidative stress in neonatal respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome of the neonate (neonatal RDS) is still an important problem in treatment of preterm infants. It is accompanied by inflammatory processes with free radical generation and oxidative stress. The aim of study was to determine the role of oxidative stress in the development of neonatal RDS. METHODS: Markers of oxidative stress and antioxidant activity in umbilical cord blood were studied in infants with neonatal respiratory distress syndrome with reference to healthy newborns. RESULTS: Status of markers of oxidative stress (malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxy guanosine) showed a significant increase with depleted levels of total antioxidant capacity in neonatal RDS when compared to healthy newborns. CONCLUSION: The study provides convincing evidence of oxidative damage and diminished antioxidant defenses in newborns with RDS. Neonatal RDS is characterized by damage of lipid, protein and DNA, which indicates the augmentation of oxidative stress. GENERAL SIGNIFICANCE: The identification of the potential biomarker of oxidative stress consists of a promising strategy to study the pathophysiology of neonatal RDS.

Correlation of serum toll like receptor 9 and trace elements with lipid peroxidation in the patients of breast diseases.

Toll-like receptors are recognized as redox sensitive receptor proteins and have been implicated in cellular response to oxidative stress. Altered pro-oxidant-antioxidant balance leads to an increased oxidative damage and consequently play an important role in breast diseases. The study was designed to access the oxidative stress status by quantification of byproducts generated during lipid peroxidation and inadequate trace elements during oxidative damage and its effects on the toll like receptor (TLR) activity in patients of breast diseases. Decreased levels of selenium, copper, zinc, magnesium and iron with elevated levels of malondialdehyde (marker of lipid peroxidation) were accompanied by decreased TLR activity in patients of benign breast diseases as well as breast carcinoma. A similar pattern was observed with the advancement of disease and its subsequent progression in breast carcinoma patients. Results of multinomial regression analysis suggest benign breast disease patients are at higher risk of developing breast cancer with high odds ratio of lipid damage.

Association between biomarkers of oxidative stress, trace elements, and cell proliferation index in patients with benign and malignant breast diseases.

OBJECTIVES: To understand the association between biomarkers of oxidative stress, antioxidants, trace elements, and cell proliferation index in relation to the disease progression in the pathophysiology of breast diseases. DESIGN AND METHODS: Concentrations of markers of oxidative stress, antioxidants, trace elements, and cell proliferation index were evaluated in the patients with benign breast diseases, malignant breast diseases, and healthy volunteers as controls. Multinomial logistic regression analysis was used to identify the contribution of the selected indexes using odds ratio and associated confidence interval. RESULTS: The level of markers of oxidative stress (malondialdehyde [MDA]) and cell proliferation index were found to be significantly higher with significantly depleted levels of antioxidants and trace elements in breast cancer patients compared with control subjects as well as benign breast disease patients. A similar pattern of changes were observed between benign and control subjects. CONCLUSION: An inadequate amount of antioxidant enzymes and trace elements may be an important contributing factor associated with oxidative stress leading to elevated levels of MDA and cell proliferation index in relation to disease progression and clinical stage in the pathophysiology of breast diseases.

Expression of serum toll-like receptor 9 and oxidative damage markers in benign and malignant breast diseases.

The intracellular redox environment plays an important role in the maintenance of proper cellular homeostasis and functions. Disturbances in redox equilibrium of cells result in pro-inflammatory conditions, and these inflammatory conditions can induce carcinogenesis or increase the malignant potential of the tumor. Oxidative stress or tissue damage can trigger toll-like receptor (TLR) family of receptors that are involved in altering the innate immune system. The present study was aimed at evaluating the level of oxidative damage markers in breast diseases by measuring the 8-hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC), malondialdehyde (MDA), and total antioxidant status (TAS) alterations in relation to expression of TLR-9. A significant increase in the level of oxidative damage markers was observed in breast carcinoma patients in comparison to benign and normal controls, which was accompanied by a significant decrease in TAS and expression of TLR-9 concentrations. 8-OHdG, PC, and MDA were negatively correlated with expression of TLR-9 and TAS levels. Altered levels of biomarkers of oxidative stress and TLR-9 among the malignant, benign, and controls suggest a correlation of oxidative stress and TLR signaling in the progression of disease in breast carcinoma patients. Receiver operating characteristic analysis depicts that expression of TLR-9 is a good indicator for distinguishing cancer patients from benign and normal controls. High accuracy, specificity, and sensitivity of oxidative stress markers and expression of TLR-9 can be used as discriminatory marker/s for efficient diagnosis.

Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation.

NF-κB p65 subunit DNA-binding activity: association with depleted antioxidant levels in breast carcinoma patients.

NF-κB is recognized as a redox-sensitive transcription factor and has been implicated in cellular response to oxidative stress. The study was designed to correlate the changes in antioxidant status with the levels of nuclear factor-κB (NF-κB) p65 subunit DNA-binding activity in relation to lymph node involvement, tumor size, and staging in breast carcinoma patients. Case control study comprised of 40 breast carcinoma patients along with 40 age- and sex-matched healthy subjects as controls. Levels of enzymatic/nonenzymatic antioxidants along with the trace elements were measured to study the antioxidant status in the study subjects. Levels of NF-κB p65 subunit DNA-binding activity was estimated by ELISA assay. The levels of enzymatic, nonenzymatic antioxidants, and trace elements were found to be significantly depleted in breast carcinoma patients in comparison to healthy controls suggesting significantly decreased levels of antioxidant activity in the breast carcinoma patients. Also, these results indicate that antioxidant levels decrease progressively with the advancement of stage and subsequent progression of disease. DNA-binding activity of NF-κB p65 subunit was higher in breast cancer patients in comparison to normal healthy controls, and the activity was found to increase with the advancement of disease. Significant correlation was observed between the DNA-binding activity of NF-κB p65 subunit and antioxidant status in the patients. The logistic regression analysis revealed decreased levels of antioxidants and increased level of DNA-binding activity of NF-κB p65 subunit were significantly associated with incidence of breast carcinoma. Depleted antioxidant status and increased level of DNA-binding activity of NF-κB p65 subunit thus point clearly of an association in relation to disease progression, clinical stage, and cytological grade in the pathophysiology of breast carcinoma.

Simultaneous progression of oxidative stress, angiogenesis, and cell proliferation in prostate carcinoma.

OBJECTIVES: To understand the association between markers of oxidative stress, levels of vascular endothelial growth factor (VEGF), and cell proliferation index in relation to disease progression, clinical stage, and cytologic grade in pathophysiology of prostate carcinoma. PATIENTS AND METHODS: Case control study comprised of 40 prostate carcinoma patients along with 40 age- and sex-matched healthy subjects as controls. Levels of 8-hydroxy-2-deoxy guanosine, protein carbonyl, and malondialdehyde along with total antioxidant status were measured to study the oxidative stress status in the study subjects. Angiogenesis was evaluated by studying the VEGF level and cell proliferation index. RESULTS: The levels of markers of oxidative stress along with VEGF and cell proliferation index were found to be significantly higher with significantly decreased levels of antioxidant activity in the study subjects in comparison with healthy controls. The results indicate oxidative stress, angiogenesis, and cell proliferation activity increase progressively with the increase in staging and progression of disease. CONCLUSIONS: Oxidative stress parameters, angiogenesis, and cell proliferation activity point clearly that with the progression of oxidative stress there is a simultaneous progression of angiogenesis, regulation and control of endothelial cell proliferation in relation to disease progression, clinical stage, and cytologic grade in the pathophysiology of prostate carcinoma.

Oxidative damage markers as possible discriminatory biomarkers in breast carcinoma.

The study was designed to evaluate the markers of oxidative damage and to establish their diagnostic utility in breast carcinoma patients. Levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG), protein carbonyl (PC), and malondialdehyde (MDA) along with total antioxidant status (TAS) were measured in breast carcinoma patients and controls. Receiver operating characteristic (ROC) analysis was done to study the diagnostic potential of the oxidative damage markers. Significant increases in oxidative damage markers were observed in breast carcinoma patients compared with the normal controls, which were accompanied by significant decrease in TAS. The logistic regression analysis revealed higher levels of oxidative stress marker and reduced level of TAS were significantly associated with breast cancer. ROC curves analysis demonstrates that 8-OHdG and PC are better indicators for distinguishing cancer patients from controls, followed by MDA and TAS. Our results indicate increased oxidative damage is associated with malignancy in breast cancer patients. High accuracy of oxidative stress markers in indicating cancer presence can be used as discriminatory makers for efficient diagnosis.

Trace elements and antioxidant enzymes associated with oxidative stress in the pre-eclamptic/eclamptic mothers during fetal circulation.

BACKGROUND & AIMS: Pre-eclampsia is associated with oxidative stress in the maternal circulation. The aim of the study was to access the oxidative stress status by quantification of byproducts generated during lipid peroxidation; deficient antioxidant activity and inadequate trace elements during oxidative damage in the umbilical cord blood of pre-eclamptic/eclamptic mothers and its effect on the fetal outcome. METHODS: In a case control study umbilical cord blood samples were collected during delivery from cases of pre-eclamptic/eclamptic mothers and from normotensive (uncomplicated pregnancy) subjects as controls. Concentrations of malondialdehyde, trace elements (Zn, Cu, Se, Mg) and antioxidant enzymes (SOD, GPx) were determined. RESULTS: Decreased levels of Zinc (p < 0.001), Copper (p < 0.001), Selenium (p < 0.005), Magnesium (p < 0.05), Superoxide dismutase (p < 0.001), Glutathione Peroxidase (p < 0.001) and elevated levels of malondialdehyde (marker of lipid peroxidation) in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies were observed. Positive correlation between Zn and SOD (Pearson r = 0.581, p < 0.001), Cu and SOD (Pearson r = 0.576, p < 0.001) and Se and GPx (Pearson r = 0.445, p < 0.005) was also observed. CONCLUSIONS: The reduced levels of trace elements associated with inadequate amount of antioxidant enzymes may be important contributing factor associated with oxidative stress leading to endothelial dysfunction in pre-eclamptic/eclamptic mothers.

Evaluation of biomarkers of oxidative stress and antioxidant capacity in the cord blood of preterm low birth weight neonates.

OBJECTIVE: The objective of the study is to investigate the association between oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of the resistance in body to oxidative damage) in the cord blood of preterm low birth weight (LBW) neonates. METHODS: Malondialdehyde (MDA), carbonyl proteins, total antioxidant capacity and Vitamin A, E and C levels in the cord blood were determined by spectrophotometry. RESULTS: Increased lipid peroxidation, protein oxidation with decreased values of vitamin A, E, C and total antioxidant capacity were observed in the preterm LBW newborns. Observations of negative correlation between MDA and protein carbonyl with antioxidants vitamin A, E and C and total antioxidant status points towards the existence of oxidative stress in the preterm LBW newborns. CONCLUSIONS: Poor fetal growth affects the development of antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative stress, which in turn may partly account for increased morbidity and mortality in these infants. The presence of an association between oxidative stress biomarkers and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW neonates suggest that increased oxidative stress may be the result of changes in the levels of certain enzymatic and non-enzymatic antioxidants due to the cause or the effect of oxidative damage occurring at the molecular level.

In vivo oxidative DNA damage and lipid peroxidation as a biomarker of oxidative stress in preterm low-birthweight infants.

OBJECTIVES: To analyze the status of oxidative stress in relation to the degree of prematurity and birthweight of neonates. MATERIALS AND METHODS: Umbilical cord blood samples were obtained at the time of delivery. 8-Hydroxy-2-deoxy guanosine (8-OHdG) has been measured as oxidative DNA damage marker in preterm low-birthweight (LBW) newborns by competitive in vitro enzyme-linked immunosorbent assay (ELISA) along with malondialdehyde (MDA) as marker of lipid peroxidation and total antioxidant status to study the oxidative stress. RESULTS: Significant elevation in the levels of 8-OHdG along with malondialdehyde has been noted in preterm LBW newborns. Serum 8-OHdG is found to be significantly and negatively correlated with birthweight (r = -0.834, p < 0.001) and gestational age of the newborn (r = -0.626, p < 0.001). CONCLUSION: These results provide evidence of increased oxidative stress in the form of DNA damage and lipid peroxidation in premature LBW newborns, which may be responsible for different complications associated with prematurity.

Vascular endothelial growth factor levels in relation to oxidative damage and antioxidant status in patients with breast cancer.

PURPOSE: Oxidative stress and angiogenesis are important elements in the pathogenesis of inflammatory diseases and cancer. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines and is up-regulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In this study, we investigated the association between oxidative stress and serum VEGF status in patients with breast cancer. METHODS: Forty patients with breast carcinoma, of which 21 were stage II and 19 were stage III, along with 40 age- and gender-matched healthy controls were enrolled. Oxidative stress, total antioxidant status, and VEGF levels in serum were evaluated by spectrophotometric procedures. Malondialdehyde (MDA) levels were measured and antioxidant status was assessed by measuring total antioxidant status (TAS) to assess oxidative damage. RESULTS: VEGF and MDA levels were significantly higher in patients with breast cancer than those of controls (p<0.005). Total antioxidant level decreased significantly in patients compared to that in controls. MDA, TAS, and VEGF levels were also analyzed based on menopausal status and different clinical disease stages. MDA and TAS level significantly different in the postmenopausal group than the premenopausal group, whereas VEGF level remained unchanged. CONCLUSION: Increased VEGF level and its positive correlation with oxidative stress level and decreased antioxidant status suggest a link between oxidative stress and malignant transformation.