Oxidative stress and antioxidants in tubercular meningitis

Oxidative stress is implicated in the etiopathogenesis of a variety of human diseases. Therefore, in the present study, erythrocyte lipid peroxidation, percentage hemolysis, antioxidant enzymes viz., glutathione reductase, glutathione peroxidase, superoxide dismutase and plasma antioxidants viz., ceruloplasmin, vitamins A,E and C have been determined in 19 patients with tubercular meningitis (TBM) and 50 normals. Six patients who were treated with antibiotics were considered for the follow up. The statistical analysis was carried out by Mann Whitney U test and Wilcoxon rank sum test. Lipid peroxidation (P<0.02), percentage hemolysis (P<0.001) and plasma ceruloplasmin (P<0.0001) of TBM patients were significantly higher, whereas erythrocyte glutathione reductase (P<0.05) and plasma antioxidant vitamins A, E and C (P<0.01, P<0.05 respectively) were significantly lower than those of the controls. In the follow up patients the glutathione reductase and catalase levels were significantly high (P<0.05) compared to their pre-treated condition. Vitamin C and E levels have attained normal range. This study indicated that the blood antioxidant status of TBM patients which was low compared to controls improved after treatment, suggesting the role of free radicals in TBM.     

Antioxidant status in neonatal jaundice before and after phototherapy

Phototherapy has been related to increased oxidative stress and lipid peroxidation. In the present study, thirty full term jaundiced neonates with appropriate weight were analyzed before and after completion of phototherapy for malondialdehyde (MDA), reduced glutathione (GSH), total thiols, vitamin C and superoxide dismutase (SOD) levels in hemolysate and albumin levels in plasma. These parameters were analyzed in cord blood samples of 20 healthy neonates as control. It was observed that levels of MDA were elevated significantly (p<0.001) in patients as compared to controls and that the levels increased significantly after phototherapy (p<0.001). Levels of SOD were also found to be increased significantly as compared to controls and the levels rose after phototherapy (p<0.001). On the other hand, the levels of non-enzymatic antioxidants such as GSH, total thiols and vitamin C were significantly low (p<0.001) as compared to controls and the levels decreased significantly after phototherapy (p<0.001). The plasma albumin levels also were found to be decreased significantly after phototherapy (p<0.01). Therefore, phototherapy increases oxidative stress and should be used with care.     

Lipid peroxidation and the levels of antioxidant enzymes in coronary artery disease

Coronary Artery Disease is the major cause of mortality and morbidity worldwide. Traditional risk factors account for only half of the morbidity and mortality from coronary artery disease. There is substantial evidence that oxidative stress plays the major role in the atherosclerotic process. The present study was undertaken to evaluate the level of lipid peroxidation (by measuring malondialdehyde) and antioxidant enzymes (ceruloplasmin, glutathione, superoxide dismutase) in coronary artery disease. Serum malondialdehyde levels and serum ceruloplasmin levels were significantly raised in all the subgroups of study group as compared to control group (p<0.001). Whole blood glutathione levels and hemolysate superoxide dismutase activity was significantly decreased in all the subgroups of study group as compared to control group (p<0.001). Above results suggests that the patients of coronary artery disease show increased oxidative stress and decreased levels of antioxidant enzymes. So it is recommended that the management protocol for coronary artery disease patients should include antioxidant supplementation along with simultaneous lowering of lipid peroxidation.     

Effect of short term supplementation of tomatoes on antioxidant enzymes and lipid peroxidation in type-II diabetes

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are rich source of Lycopene, relatively a new carotenoid known to play an important role in human health and disease. In this study lipid peroxidation rate was measured by estimating Malondialdehyde and the levels of serum enzymes involved in antioxidant activities like Super Oxide Dismutase, Glutathione Peroxidase, Glutathione Reductase, Reduced Glutathione, in type-II diabetic group (n=40) and age matched control group (n=50), and observed significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in type-II diabetes when compared to control group (p<0.001). Short term supplementation with tomatoes (cooked) to diabetic group for a period of 30 days, showed a significant improvement in antioxidant enzyme levels (p<0.001) and decreased lipid peroxidation rate (p<0.001) suggesting the supplementation with tomato lycopene may serve as the best method of preventing the oxidative stress in diabetic patients.     

Blood lipid peroxidation products and antioxidants in senile cataract

Lipid peroxidation products and antioxidants were estimated in either blood, serum or erythrocytes of 25 cases of early and 25 of advanced senile (50–60 years) cataract and 30 persons of age matched healthy controls. Serum lipid peroxidation products (as malondialdehyde) were significantly higher in patients with early senile (0.25±0.05 μm/dl, P<0.05) and advanced senile cataract (0.29±0.05 μm/dl, P<0.001) as compared to healthy controls (0.22±0.07 μm/dl). Erythrocyte superoxide dismutase levels were lower in patients with early senile (730±60.5 units/gm Hb) and significantly lower in advanced senile (712±50.2 units/gm Hb, P<0.05) cataract than those in healthy controls (767±59.5 units/gm Hb). Serum α-tocopherol was significantly lower (P<0.05) in only advanced senile cataract (0.69±0.08 mg/dl) but not in early senile cataract (0.75±0.08 mg/dl) when compared with healthy controls (0.75±0.09 mg/dl). There was no significant difference in the erythrocyte concentration of reduced glutathione and serum levels of total proteins, β-carotene, vitamin A, ascorbic acid, calcium, magnesium and zinc.     

Paraoxonase activity and antibodies to oxidized-LDL in chronic renal failure patients on renal replacement therapy

Serum paraoxonase (PON1) and antibodies to oxidized-LDL (anti ox-LDL) were measured in chronic renal failure subjects on renal replacement therapy such as hemodialysis (HD) peritoneal dialysis (PD) and transplantation (Txp). Paraoxonase activity was significantly lower in HD and PD group (P<0.001) than in control subjects. In transplant patients, paraoxonase activity was not significantly different from that of controls. Antibodies to ox-LDL was significantly higher in HD, PD and Transplant patients (P<0.0001) compared to control subjects. High titers of antibodies were observed in the HD group compared to the PD and Transplant subjects. A decrease in paraoxonase activity and high titers of Antibodies to ox-LDL in the dialysis group suggest a decreased cardio protective effect of HDL and enhanced risk of premature cardiovascular complications. Whereas in case of transplant subjects, there seems to be restoration of PON1 activity, but elevated levels of anti-oxLDL could still be a potential atherogenic factor. Hence, we propose that estimation of these two parameters can be used as a useful index to measure the cardiac risk in the above patient category     

Evaluation of oxidative stress in pregnancy induced hypertension

This work was undertaken to investigate correlation between oxidative stress and initiation of pathogenesis of pregnancy induced hypertension (PIH). Fifty primigravidae in age group of 20–35 years and gestational age 28–42 weeks with PIH were taken as cases. Twenty healthy primigravidae with no medical and surgical complications of pregnancy and with blood pressure ≤140/90 mm Hg served as controls. The cases were again subgrouped as severe preeclampsia (12 in number) and mild pre-eclampsia (38 in number). All of them were evaluated for serum malondialdehyde (MDA), Serum vitamin E and plasma vitamin C levels. The serum MDA levels were raised significantly in women with mild preeclampsia (P<0.01) and in women with severe preeclampsia (P<0.01) in comparison to normal primi gravida. The serum vitamin E levels were decreased in primi gravida with mild preeclampsia (p<0.1) and in primi with severe pre eclampsia (P<0.1) in comparison to normal primi gravida but the fall was not statistically significant. There was a significant fall (P<0.05) in the vitamin C levels in primi with mild preeclampsia than in the normal primi. The vitamin C levels in severe preeclamptic patients were lower than the normal primi but the fall was not statistically significant (P=0.10). The serum MDA and vitamin E showed a negative correlation in all the cases. The serum MDA and plasma vitamin C also showed a negative correlation in the control and study group. This observation suggests that in hypertensive disorders of pregnancy there is an imbalance between lipid peroxidation and antioxidant vitamin status because of oxidative stress. The decreased serum concentrations of the antioxidant vitamins supports the hypothesis that lipid peroxidation is an important causative factor in the pathogenesis of preeclampsia. The rise in antioxidants is probably to compensate the increased peroxide load in severe preeclampsia.     

Changes in serum copper levels in patients with malignant diseases undergoing radiotherapy

Present study repots changes in serum copper levels (SCL) in various neoplastic diseases undergoing radiotherapy. We estimated SCLs in 140 individuals comprising of 90 previously untreated patients with various malignancies and 50 healthy controls. Patients received radiation in doses of 40–70 Gy in 4–7 weeks. SCLs were again estimated in patients following irradiation. The mean SCL was significantly higher (P<0.001) in cancer patients as compared to healthy controls. It declined significantly (P<0.001) following irradiation. However, it remained significantly higher as compared to healthy controls (P<0.01). Highest fall in SCL was seen in complete clinical responders and least in non-responders to radiation treatment. Serial estimation of SCLs may be useful in the treatment monitoring of the neoplasms undergoing radiation treatment.     

Oxidants and antioxidants in hypoxic ischaemic encephalopathy

In the present study, the role of serum lipid peroxide and serum nitric oxide as oxidants and erythrocytic superoxide dismutase & serum vitamin E as antioxidants were determined in the 50 neonates with hypoxic ischaemic encephalopathy. (HIE) as against 25 healthy neonates as controls 50 patients of HIE were further divided into two groups i. e. mild and moderate HIE patients. All subjects were in the age group of 37–41 weeks of gestation. The levels of serum lipid peroxide, serum nitric oxide and erythrocytic superoxide dismutase were significantly elevated in both groups of neonates with HIE than those of controls (P<0.001), whereas serum vitamin E levels were significantly decreased in both groups of HIE patients than those of controls (P<0.001). A positive correlation was obtained between serum lipid peroxide and erythrocytic superoxide dismutase (r=+0.86). Alterations in the status of oxidants and antioxidants indicate role of free radicals in the development of HIE.     

Role of reactive oxygen species in pathogenesis of nephrotic syndrome

Nephrotic syndrome is the common chronic disorder characterized by alteration of permeability of the glomerular capillary wall, resulting in its inability to restrict the urinary loss of proteins. Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia associated with peripheral edema. The molecular basis of glomerular permselectivity remains largely unknown. In recent years it has been proposed that Nephrotic syndrome is a consequence of an imbalance between oxidant and antioxidant activity. The present study was aimed to test that the reactive oxygen species are the mediators of excessive protein permeability and other complications of Nephrotic syndrome. For this 30 adults with Nephrotic syndrome were studied. The control group comprised 30 healthy adults matched for age. Serum levels of lipid peroxides, nitric oxide (NO⊙), α- tocopherol, ascorbic acid, erythrocyte superoxide dismutase activity, serum albumin, uric acid, cholesterol and plasma total antioxidant capacity were measured. Student’s ‘t’ test was applied for statistical analysis. There was a significant increase in lipid peroxide (1.58 ± 0.42 in controls, 3.64 ±1.3 in patients) (P<0.001) levels in study group as compared with controls. α-tocopherol (12.95 ± 1.04 in controls, 9.93 ± 1.43 in patients) (P<0.001), erythrocyte SOD activity(1.88 ± 0.9 in controls 1.07 ± 0.5 in patients) (P=0.01), serum albumin(4.06 ± 0.50 in controls, 3.04 ± 0.11 in patients) (P<0.001), and plasma total antioxidant capacity (847.33 ± 126.83 in controls, 684.00±102.94 in patients) (P<0.001) were significantly decreased. There was non-significant increase in uric acid (P>0.05), a non-significant decrease in NO⊙ (38.48 ± 15.47 in controls 37.47 ± 14.27 in patients) (P>0.05) and ascorbic acid levels ascorbic acid,( 0.95 ± 0.31in controls 0.79 ± 0.30 in patients) (P>0.05) in study group as compared with controls. Imbalance between oxidants and antioxidants may contribute to pathogenesis of proteinuria and related complications in nephrotic syndrome.     

Maternal and fetal indicators of oxidative stress in various obstetric complications

The present study demonstrates the incidence of increased lipid peroxidation and protein oxidation in both maternal and fetal erythrocytes as markers of oxygen radical activity in different complications of pregnancy. In fetuses born after premature rupture of membranes, lipid peroxidation was significantly elevated as indicated by increased malondialdehyde levels (p<0.05) as compared to controls. Proteolytic activity in the erythrocytes of mothers in this group was also significantly high (p<0.01). In patients delivered by lower segment cesarian section, lipid peroxidation and proteolytic activity in maternal erythrocytes were significantly high (p<0.05 and p<0.001 respectively). In patients with prolonged second stage of labour, lipid peroxidation and proteolytic activity in maternal erythrocytes was significantly higher than in controls (p<0.001 and p<0.05 respectively). In this group, endogenous protein damage due to oxidative stress was significantly high both in the mother and the fetus (p<0.001 and p<0.05 respectively).     

Association of Iron Overload with Oxidative Stress,Hepatic Damage and Dyslipidemia in Transfusion-Dependent β-Thalassemia/HbE Patients

Blood transfusion can be a life-saving therapy for β-thalassemia major and β-thalassemia/HbE (β-TM) patients with chronic anemia, major caused severe iron overload particularly in β-TM patients received only blood transfusion therapy. We aim to evaluate the association of iron overload with oxidative stress, liver damage, and elevated very low density lipoprotein cholesterol (VLDL-C) in transfusion-dependent β-TM patients. Serum ferritin, malondialdehyde (MDA), liver profiles, triglycerides levels, and VLDL-C were significantly higher while total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and total antioxidant capacity were lower in β-TM than controls. Serum ferritin was significantly correlated with MDA, liver enzymes and lipid profiles (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these β-TM patients, independent predictors of iron overload were MDA (β = 0.410, r ² = 0.671, p < 0.001), ALT (β = 0.493, r ² = 0.578, p < 0.001), and VLDL-C (β = 0.253, r ² = 0.711, p < 0.001). In conclusion, iron overload associated with increased oxidative stress, lipid peroxidation, liver damage, decreased TC, LDL-C, HDL-C and over production of VLDL-C, is significantly problem in transfusion-dependent β-TM patients. These appeared the major cause of future morbidity and mortality in β-TM patients.     

Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients

Presence of oxidative stress in type 2 diabetes mellitus (DM) is well proved. Current study was undertaken to know the relation between fasting plasma glucose (FPG) and copper along with antioxidants like total thiols and ceruloplasmin, and antioxidant enzyme glutathione S transferase (GST). The study group consisted of a total of 201 subjects which included nondiabetic healthy control subjects (n = 78) and diabetic patients (n = 123). Plasma total thiols, GST, copper and ceruloplasmin levels were measured all the subjects using spectrophotometric methods and FPG levels were determined in clinical chemistry analyzer Hitachi 912. There was significant increase in FPG (P<0.001) and copper (P<0.001) and decrease in ceruloplasmin (P<0.001) and protein thiols (P<0.001) in type 2 DM cases compared to healthy controls. There was no significant change in GST between type 2 DM cases and controls. There was significant negative correlation of FPG with antioxidants like ceruloplasmin (r = −0.420, P<0.001) and total thiols (r = −0.565, P<0.001). Protein thiols correlated positively with ceruloplasmin (r = 0.364, P<0.001). Our study indicates possible increase in copper mediated generation of ROS leading to increased consumption of available antioxidants in the body.     

Plasma MDA and antioxidant vitamins in diabetic retinopathy

Hyperglycemia and dyslipidemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation, an important mechanism in genesis of microangiopathy. We took up a study on oxidative stress, measured by plasma MDA and antioxidant vitamin status in type − 2 DM patients with and without retinopathy and compared them with a control non-diabetic group. Lipid peroxidation marker MDA was significantly elevated (p < 0.001) in both the diabetic groups whereas, serum vitamin E and vitamin C registered a significant fall (p<0.001) as compared to controls. Our correlation study revealed a significant positive association between plasma MDA with both fasting and 2hr post prandial plasma glucose (r=0.81, p < 0.001, r=0.92, p <0.001) suggesting the role of hyperglycemia in free radical production. Plasma MDA also depicted significant positive relation (p< 0.001) with all lipid parameters except serum HDLc pointing the role of dyslipidemia towards lipid peroxidation. Plasma MDA level was also found to be negatively correlated with both the vitamins (p<0.001, p<0.001) in the study group explaining their protective consumption in the oxidative process prevailing in diabetic retinopathy.     

An opium alkaloid-papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress

In this communication, we show the modulatory potential of papaverine, an opium alkaloid and a well known vasodilator agent on the ethanol-induced hepatic oxidative stress in male Wistar rats. Ethanol treatment (50% v/v) enhanced lipid peroxidation significantly accompanied by a decline in the activities of glutathione peroxidase (G-Px), glutathione reductase (GR) and depletion in levels of hepatic glutathione (GSH). Ethanol administration increased hepatic glutathione-s-transferases (GST). Enhanced lipid peroxidation induced by ethanol was significantly reduced when papverine was coadministered (P<0.05). In addition, the depleted levels of glutathione and inhibited activities of G-Px and GR recovered significantly (P<0.05) levelling off to control values on co-exposure. Papaverine (200 mg/kg bw) effectively antagonised the ethanol-induced lipid peroxidation and impaired glutathione levels and glutathione dependent enzyme systems. Our results suggest that papaverine is an effective chemopreventive agent in the liver and may suppress the ethanol-induced hepatotoxicity.     

Effect of oral antioxidant supplementation on lipid peroxidation during radiotherapy in head and neck malignancies

The objectives of the present study were to ascertain the variations in the serum levels of malondialdehyde and total antioxidant status, in head and neck malignancies with different stages, with and without oral antioxidant supplementation, before and after radiotherapy, and to validate the protective effects of an antioxidant supplementation during radiotherapy. The pretreatment values of serum malondialdehyde were significantly raised, while that of serum total antioxidant status were significantly declined in all the stages of head and neck malignancies, when compared with the healthy controls values (P<0.001). A significant correlation was observed related to the studied parameters and different stages of the disease. The study suggests that an oral antioxidant supplementation during radiotherapy is an effective mode in reducing oxidative stress. Antioxidant supplementation during radiotherapy may serve as an adjuvant therapy in malignancies offering a protection to normal cells that may further reduce the risk of developing secondary cancers.     

Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine

The aim of this study was to evaluate the radioprotective effect of turmeric extract (40 mg/kg body weight) and vitamin E (α- tocopherol acetate, 400 IU/kg body weight) supplementation on lipid peroxidation, reduced glutathione and antioxidant defense enzymes in various organs like liver, kidney and salivary glands at 24 h in adult Swiss mice. ¹³¹Iodine exposure significantly increased lipid peroxidation in kidney and salivary glands in comparison to control animals. Pre supplementation with turmeric extract for 15 days showed significant lowering of lipid peroxidation in kidney. On the other hand vitamin E pre supplementation showed marked reduction in lipid peroxidation in salivary glands. Reduced glutathione levels decreased significantly in liver after radiation exposure. However, pre supplementation with turmeric extract and vitamin E did not improve glutathione levels in liver. In conclusion, we have observed differential radioprotective effect of turmeric extract and vitamin E in kidney and salivary glands. However, Vitamin E seems to offer better radioprotection for salivary glands which is known to be the major site of cellular destruction after radioiodine therapy in patients.     

Effect of supplementation of vitamin C and E on oxidative stress in osteoporosis

Osteoporosis encompasses a wide spectrum of conditions associated with imbalance of osteoclastic and osteoblastic activities. The increased activity of osteoclasts leads to increased free radical formation and hence lipid peroxidation. Present study probes into the role of antioxidants as a palliative treatment for osteoporosis. It involved 50 healthy controls and 75 clinically diagnosed osteoporosis patients. Both the groups underwent baseline assessment of biochemical markers viz. osteoblastic markers: serum Alkaline phosphatase. Free or ionic calcium and Inorganic phosphorus, osteoclastic markers: serum Tartarate resistant acid phosphatase and Malondialdehyde and the antioxidant status: serum Superoxide dismutase and Erythrocyte reduced glutathione. The osteoporotic group was then divided into groups A (Vitamin E-Evinal 400 mg), B (Vitamin C-Celin 500 mg), C (Vitamin E+C-Evinal+Celin) for antioxidant supplementation for a period of 90 days. The results reveal that there is significant fall in concentration of serum MDA (p<0.001), TrACP (p<0.01). Improvement in antioxidant status is reflected by significant rise in concentration of serum SOD (p<0.001) and erythrocyte GSH (p<0.001) after 90 days of antioxidant supplementation in osteoporosis. The findings indicate that on the whole bone status improved with prolonged antioxidant vitamin supplementation, which can be used as a palliative treatment for osteoporosis. The efficacy is not affected whether the vitamins are administered singly or conjointly.     

Role of oxidative stress and antioxidants in aetiopathogenesis and management of oral submucous fibrosis

Lipid peroxidation product, malonaldehyde (MDA) and antioxidants were estimated in plasma and erythrocytes of 34 cases of oral submucous fibrosis (OSMF) of different grades with equal number of healthy controls to evaluate the association of reactive oxygen species (ROS) and OSMF. While plasma MDA was found to be significantly higher in patients (3.3±0.4 nmole/ml, P<0.001) as compared to controls (2.4±0.5 nmole/ml), plasma beta carotene and vitamin E levels were found to be decreased significantly in patients (81.7±14.3 μg/100 ml, P<0.001; 9.3±0.9 mg/L, P<0.01 respectively) with respect to healthy controls (110±20.8 μg/100 ml and 10.1±1.2 mg/L). The decrease in beta-carotene and vitamin E was found to be more significant in OSMF grade II and III than in grade I. After 6 weeks of oral administration of beta-carotene and vitamin E, patients showed increase in plasma level of these two antioxidants along with decrease in MDA level associated with clinical improvement.     

Oxidative stress and calcium-phosphorus levels in Rheumatoid arthritis

Generation of reactive oxygen species is an important factor in the development and maintenance of rheumatoid arthritis (RA) in humans. This study was undertaken to investigate interplay among oxidants, antioxidants and pathogenesis of Rheumatoid arthritis. Serum levels of lipid peroxides, nitric oxide, vitamin E and ratio of calcium/phosphorus in RA patients were determined and compared with normal healthy controls. Significant increases in lipid peroxides (p<0.001) and nitric oxide (p<0.001) levels were found in patients presenting with RA as compared to controls. Whereas significant decrease in vitamin E (P<0.001) and calcium/phosphorus ratio (p<0.001) were found in Rheumatoid arthritis patients as compared to controls. Positive correlation was found between lipid peroxides and nitric oxide as well as between vitamin E and calcium. While lipid peroxides and nitric oxide were correlated negatively with vitamin E. whereas negative correlation was observed between MDA and Calcium/Phosphorus ratio in patients with rheumatoid arthritis. Our findings suggest that there is a close association between bone loss and oxidative threat in patients presenting with Rheumatoid arthritis.