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1.
Reactive oxygen species (ROS) cause damage to the DNA producing mutations and formation of tumours such as carcinoma of breast. Tumour cells are known to produce ROS at a greater pace than the non-transformed cells. The increased production of reactive oxygen species causes oxidative stress leading to cell proliferation and hence increased inflammatory conditions. The present study was aimed to investigate the role of oxidative stress in the pathogenesis of breast cancer. Females suffering from breast cancer had significantly decreased Superoxide dismutase (SOD) and reduced glutathione (GSH) levels in comparison to normal females. The compromised antioxidant defence system produces the oxidative stress which in turn creates the inflammatory response shown by concomitant increased adenosine deaminase (ADA) activity in female patients. ADA diminishes the protective molecule adenosine. There were significant variations (p < 0.01) in ADA activity with different clinical stages (stage 1–4) of breast cancer suggesting thereby that estimation of ADA activity can be used as a diagnostic tool to detect the stage of cancer along with cytological studies. Mastectomy was performed and post-operatively serum SOD and ADA activity and plasma GSH levels were estimated. There was a statistically significant increase in activity of SOD and levels of GSH while serum ADA activity decreased significantly, suggesting thereby that oxidative stress is responsible for increased cell proliferation and hence the inflammatory conditions in CA breast that got ameliorated post-operatively.  相似文献   

2.
The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa and contaminating leukocytes has been defined as one of the few etiologies for male infertility. Administration of antioxidants in patients with ‘male factor’ infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. Mammalian spermatozoa membranes are very sensitive to free radical induced damage mediated by lipid peroxidation, as they are rich in polyunsaturated fatty acids. Limited endogenous mechanisms exist to reverse these damages. ROS attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. ROS induced DNA damage accelerate the germ cell apoptosis. Unfortunately spermatozoa are unable to repair the damage induced by excessive ROS as they lack the cytoplasmic enzymes required to accomplish the repair. Assessment of such oxidative stress status (OSS) may help in the medical treatment. Treatment strategies must be directed toward lowering of ROS levels to keep only a small amount necessary to maintain normal cell function.  相似文献   

3.
In this study we have modified DNA by exposing it to ultraviolet light in the presence of hydrogen peroxide. The modified DNA was probed for binding to the antibodies present in the sera of patients suffering from various types of cancer. Higher recognition of modified DNA, as compared to native DNA, by antibodies from cancer patients has got far reaching significance.  相似文献   

4.
Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O2−) and hydroxyl radical (HO·) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton’s reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H2O2-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (P<0.001) protected the lipid peroxidation in all the tissue homogenate/mitochondria. The extract at 2 and 0.5 mg/ml could protect 92 % of the lipid peroxidation in brain homogenate and liver mitochondria respectively. The percent inhibition of lipid peroxidation at 1mg/ml of Z. officinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.  相似文献   

5.
The correlation between antioxidant capacity and oxidative damage during aging has been reported in several tissues in different species. Glutathione-S-transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione (GSH). We observe a significant (P < 0.001) increase in plasma GST activity as a function of human age (r = 0.5675). A significant (P < 0.001) positive correlation (r = 0.8979) is observed between GST activity and total plasma antioxidant potential measured as ferric reducing ability of the plasma (FRAP). GST activity and red cell intracellular GSH also show a significant positive correlation (r = 0.7014). We hypothesize that the increased activity of plasma GST is a manifestation of increased generation of ROS and a concomitant decrease in the level of plasma antioxidant capacity during aging.  相似文献   

6.
As the oxygen tension of inspired air falls with increasing altitude in normal subjects, hyperventilation ensues. This acute respiratory alkalosis, induces increased renal excretion of bicarbonate, returning the pH back to normal, giving rise to compensated respiratory alkalosis or chronic hypocapnia. It seems a contradiction that so many normal people at high altitude should permanently live as chronic acid–base patients. Blood gas analyses of 1,865 subjects at 3,510 m, reported a P aCO2 (arterial carbon dioxide tension ± SEM) = 29.4 ± 0.16 mmHg and pH = 7.40 ± 0.005. Base excess, calculated with the Van Slyke sea level equation, is −5 mM (milliMolar or mmol/l) as an average, suggesting chronic hypocapnia. THID, a new term replacing “Base Excess” is determined by titration to a pH of 7.40 at a P aCO2 of 5.33 kPa (40 mmHg) at sea level, oxygen saturated and at 37°C blood temperature. Since our new modified Van Slyke equations operate with normal values for P aCO2 at the actual altitude, a calculation of THID will always result in normal values—that is, zero.  相似文献   

7.
Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. There are some primary antioxidants such as glutathione peroxidase (GPx), glutathione S-transferases (GSTs) and reduced glutathione, which protect against callular and molecular damage caused by the reactive oxygen metabolites (ROMs). The present study was conducted to determine the level of malondialdehyde (MDA), as an index of lipid peroxidation, along with the GPx, GSTs activities and level of reduced glutathione in 45 prostate cancer (PC) patients, 55 benign prostate hyperplasia (BPH) patients as compared to the controls. Significant higher levels of MDA and GSTs activities in the serum, (P<0.005) and significant lower levels of reduced GSH concentration and GPx activity in blood haemolysates (P<0.05) of PC and BPH patients were observed as compared to the controls. The relatively higher GSTs activity and low level of reduced GSH may be due to the response of increased reactive oxygen metabolites production in the blood. The higher MDA and lower GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the*OH radical followed by MDA. This result hypothesizes that oxidant-antioxidant imbalance may be one of the major factor responsible for the development of prostate cancer and benign prostate hyperplasia.  相似文献   

8.
The present study was designed to probe the possible role of singlet oxygen and superoxide anion radical modified DNA in the etiopathogenesis of Systemic lupus erythematosus. These species were generated by the exposure of riboflavin to 365 nm UV light. Modified DNA showed single strand breaks, hyperchromicity at 260nm and decrease in Tm. The modified DNA induced high titer antibodies in experimental animals. The antibodies showed reactivity with various nucleic acid polymers, a property commonly associated with Systemic lupus erythematosus anti-DNA autoantibodies. Systemic lupus erythematosus sera showed preferential binding of modified DNA over native DNA in direct binding and competitive binding solid phase immunoassays and band shift assays. The results suggest for the possible involvement of the singlet- superoxide modified DNA as a potential trigger for anti- DNA autoantibody production in SLE and thus in the etiopathogenesis of the disease.  相似文献   

9.
The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited.  相似文献   

10.
Reactive oxygen species are thought to be involved in the pathogenesis of Malaria. To assess the extent of oxidative stress, a study was conducted in patients withPlasmodium falciparum malaria andPlasmodium Vivax malaria. Plasma Thiobarbituric acid reactive substances (TBARS) were measured to assess the degree of lipid peroxidation. Antioxidant status was measured by estimating the levels of Vitamins E and C. Results were compared with age and sex matched control subjects. This study suggests that plasma TBARS levels were significantly increased in malaria patients. The patients withP. falciparum infection showed significantly increased levels of lipid peroxides when compared toP. vivax malaria. The antioxidant Vitamins E and C were decreased significantly in malaria patients in both the groups. Maximum decline in Vitamin C was observed inP. vivax malaria. Therefore it is been hypothesized that antioxidant Vitamins E and C could provide protection against the oxidative stress induced by malaria.  相似文献   

11.
Increased levels of plasma DNA have frequently been noticed in the blood plasma of cancer patients. The possibility of using plasma DNA level as the indicator of tumor stage in breast cancer was investigated in plasma samples obtained from 100 breast cancer patients and 100 healthy women who were included as controls. Circulatory plasma free DNA was extracted from plasma samples and quantified by fluorometer. The median concentration of plasma DNA in the plasma samples from breast cancer patients classified by TNM staging system as stage I, II, III, IV and breast surgical patients were 0.5, 235, 422, 1,280 and 0.5 ng/ml, respectively. The level of plasma DNA in the stage II- IV group was significantly higher than those in the surgical group with breast cancer and control group (P value < 0.001). The plasma DNA concentration in stage II, III and IV of breast cancer were higher when compared with healthy group. These tumor size, TNM stage and metastasis were significantly correlated with plasma DNA. The cut point of 120 ng/ml was early screening and treatment follow up breast cancer.  相似文献   

12.
Microvascular and macrovascular diseases are the main causes of morbidity in type 2 diabetes patients through chronic hyperglycaemic condition via oxidative stress and inflammation. Reactive oxygen species (ROS) activate p38 MAPK phosphorylation and inflammation which enhances protein modification by carbonylation. The use of metformin and a p38 MAPK inhibitor is hypothesised to reduce ROS production and inflammation but effects of metformin and p38 MAPK inhibitor (SB203580) on ROS production and inflammation in vascular type 2 diabetes mellitus non-obese (T2DM) have not been investigated. The Goto-Kakizaki rat T2DM model was divided into three groups as T2DM, T2DM treated with 15 mg/kg bw metformin and T2DM treated with 2 mg/kg bw SB203580 for 4 weeks. Rat aortas were isolated and protein carbonyl (PC) contents were measured by spectrophotometric DNPH assay. Aortic IL-1ß level was determined by ELISA. Results showed that aortic PC contents in the T2DM group were significantly higher than in non-diabetic rats. Treatment with metformin or SB203580 significantly reduced PC contents while only metformin significantly reduced IL-1ß levels. Findings indicated that metformin reduced ROS production and inflammation in diabetic vessels and possibly reduce vascular complications in non-obese T2DM.  相似文献   

13.
High plasma concentration of low-density lipoprotein (LDL) is associated with increased risk of atherosclerosis. Modified forms of LDL, especially oxidized LDL play a major role in its pathogenesis. This article gives detailed insight into the kinetics ofin vitro LDL oxidation by copper at different concentrations in normal and high-risk group subjects. Basal level of oxidatively modified LDL was significantly higher in ischaemic heart disease (IHD) and IHD hyperlipidemic subjects compared to normolipidemic and, hyperlipidemic control subjects, respectively. Derivatization of amino groups of apo-lipoprotein as monitored by estimating free amino groups concentration, was significantly higher in high-risk group and established IHD cases. Kinetics of oxidation was studied with two different concentrations of CuSO4 (2.5 mM and 7.5 mM). thiobarbituric acid reactive substances (TBARS) level increases with time, and up to 95% oxidation was observed in 8 hr. About 60–65% less free amino groups were observed in native-LDL isolated from IHD patients compared to normal subjects. Study also showed an increase in two oxidative products studied, 20α-OH-cholesterol and 4-cholesten-3-one with oxidation time accompanied by corresponding decrease in LDL cholesterol. Increase in oxidative species was more evident in high-risk group and IHD patient. Basal level of oxidatively modified LDL measured in terms of TBARS was significantly higher in present study, strongly support that the extent of LDL oxidation monitored as TBARS and FAG level in circulating-LDL could be used as risk marker for high risk group.  相似文献   

14.
Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus. Even though many ethological factors have been attributed for the pathogenesis of this disease no attempts were made to correlate DNA damage as a causative factor. Hence the present study was undertaken to asses the extent of somatic DNA damages by cytokinesis-block micronuclei assay (CBMN). An attempt is also being made to correlate the habits and/or risk factors and socioeconomic status with CAN. The CBMN frequency of 46 patients suffering from autonomic neuropathy was compared with that of 25 healthy age and sex matched controls. All the subjects were suffering from type 2 diabetes for at least 8 years and have varying degrees of coronary artery diseases. The mean CBMN frequency of the patients was statistically higher than that of the healthy control subjects (P < 0.05). The CBMN frequency was found to be significantly altered in CAN patients who where physical inactivity and smoking. A significant correlation could also be observed between CAN and smoking, diabetes mellitus, hypertension, dyslipidemia, abdominal obesity, and physical activity.  相似文献   

15.
The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies. Herein, we designed a cascade-responsive ROS nanobomb (ZnO2@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The calcium phosphate shell and ZnO2 core gradually degrade and release Ca2+, Zn2+ and hydrogen peroxide (H2O2) under acid stimulation. On the one hand, Zn2+ can enhance the generation of endogenous superoxide anions (·O2–) and H2O2 through the inhibition of the mitochondrial electron transport chain. On the other hand, the generation of large amounts of exogenous H2O2 can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy. In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca2+ in cells and further result in Ca2+ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the ‘domino effect’ that caused multiple heavy ROS storms and Ca2+ overload in tumors and effectively activated anti-tumor immune response.  相似文献   

16.
Reactive oxygen species (ROS) are known to be a key factor in the development of cancer, and many exogenous sources are supposed to be related to the formation of ROS. In this paper, a microfluidic chip was developed for studying the production of ROS in lung cancer cells under different chemical and physical stimuli. This chip has two unique features: (1) five relative concentrations of 0, 1/8, 1/2, 7/8, and 1 are achieved in the culture regions; (2) a shear stress gradient is produced inside each of the five culture areas. Lung cancer cells were seeded inside this biocompatible chip for investigating their response to different concentrations of H2O2, a chemical stimulus known to increase the production of ROS. Then the effect of shear stress, a physical stimulus, on lung cancer cells was examined, showing that the production of ROS was increased in response to a larger shear stress. Finally, two antioxidants, α-tocopherol and ferulic acid, were used to study their effects on reducing ROS. It was found that high-dose α-tocopherol was not able to effectively eliminate the ROS produced inside cells. This counter effect was not observed in cells cultured in a traditional chamber slide, where no shear stress was present. This result suggests that the current microfluidic chip provides an in vitro platform best mimicking the physiological condition where cells are under circulating conditions.  相似文献   

17.
Vitiligo is an idiopathic, acquired, circumscribed, hypomelanotic skin disorder, characterized by milky white patches of different sizes and shapes. It is due to the destruction of melanocytes resulting in the absence of pigment production of the skin and mucosal surfaces. Oxidative stress has been implicated in pathophysiology of vitiligo. To study the activity of blood Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) in vitiligo patients. A case–control study was conducted in which 100 patients were enrolled after written consent. 50 cases were of active vitiligo and 50 served as control (25 healthy control and 25 with stable vitiligo). SOD—In our study, among the active vitiligo cases 90% had high level of SOD and 10% had normal level of SOD. Among the stable vitiligo controls, 92% had normal level of SOD and 8% had low levels of SOD.The difference between active vitiligo cases and stable vitiligo control as well as with healthy control was statistically significant (P value < 0.05). GPx—Among the active vitiligo cases 74% had normal GPx levels, 22% had low and only 4% had high levels of GPx. Among the stable vitiligo controls, 64% had normal GPx levels, 16% had low, and 20% had high levels of GPx. The difference between active vitiligo cases and stable vitiligo control as well as with healthy control was statistically not significant (P value > 0.05). Our study shows that oxidative stress is involved in the pathophysiology of vitiligo, as indicated by the high levels of serum superoxide dismutase activity.  相似文献   

18.
Reactive oxygen species (ROS) formed in various metabolic reactions cause unlimited damage by attacking and oxidizing the macromolecules. An arsenal of antioxidant substances neutralizes these ROS at various sites of their metabolic cascade, and if disequilibrium exists between the pro and antioxidant system, oxidative stress persists. The present study was undertaken in schizophrenia, to highlight the response and role of some endogenous antioxidants viz. reduced glutathione (GSH), bilirubin, total proteins, albumin and uric acid in scavenging the ROS. The effect of severity of disease, age factor, and substance abuse was also studied. In all, 50 schizophrenics and 50 age and sex-matched controls were enrolled in the present study. Fasting blood samples were drawn for estimating malondialdehyde (MDA), GSH, bilirubin, total proteins, albumin and uric acid in both the groups. The results were statistically analyzed by Z-test and correlated using correlation coefficient (r). The study shows reduction in MDA levels and decline in the level of endogenous antioxidants, but within the normal range. Chronic schizophrenics were at a higher risk of oxidative stress and age and substance abuse seems to worsen the situation.  相似文献   

19.
Impact of Chronic Lead Exposure on Selected Biological Markers   总被引：1，自引：0，他引：1  
Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70 years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0–10 μg/dl), Group B (BLL: 10–20 μg/dl). Group C (BLL: 20–30 μg/dl) and Group D (BLL: 30–40 μg/dl) having BLLs of 3.60 ± 2.71 μg/dl, 15.21 ± 2.65 μg/dl, 26.82 ± 2.53 μg/dl and 36.38 ± 2.83 μg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (P < 0.001), while the ZPP level was significantly higher with increased BLL (P < 0.001). Further, BLL showed a negative correlation with δ-ALAD (r = −0.425, P < 0.001, N = 250) and a positive correlations with ZPP (r = 0.669, P < 0.001, N = 250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress.  相似文献   

20.
HIV-infected adults may be likely to have metabolic syndrome (MS) at younger ages and in the absence of obesity compared with general population. In the present study, we determined prevalence of MS and its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1 infected patients with different ART status. We used plasma level of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as a biomarker of oxidative DNA damage. To measure plasma 8-OHdG we used 8-OHdG enzyme-linked, immunosorbent assay. The biomarkers of MS were insulin resistance, Cholesterol/HDL ratio, Waist circumference and Hypertension. MS and oxidative DNA damage were significantly higher in HIV-positive patients with second line ART and first line ART than ART-naive patients. In a logistic regression analysis, increased MS was positively associated with the increased DNA damage (OR: 29.68, 95%:13.47, CI: 65.40) P = 0.0001. ART plays a significant role in the development of MS and oxidative DNA damage in HIV-positive patients taking antiretroviral therapy. Awareness and knowledge of MS and DNA damage in HIV/AIDS patients may prove helpful to clinicians to manage non-AIDS diseases such as cardiovascular disease and cancer. To determine exact role of ART in induction of MS and DNA damage larger studies are warranted.  相似文献   

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