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     

Kinetic analysis of LDL oxidation in IHD and IHD risk subjects in Indian population

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.     

Effect of yoga training on plasma lipid profile,R.B.C. membrane lipid peroxidation and Na+K+ ATPase activity in patients of essential hypertension

We conducted a controlled study on effect of selected yoga practive in the control and management of 50 cases of essential hypertension and equal number of healthy (nonhypertensive) controls. Free radical cellular damage is considered to be the underlying common biological factor in essential hypertension. We, therefore, investigated lipid profile lipid peroxidation and Na⁺K⁺ ATPase activities of plasma membrane of subjects with essential hypertension. It was found that hypertensive subjects had an elevated lipid peroxidation and decreased Na⁺K⁺ ATPase activity in plasma membrane as compared to normotensive healthy controls, the specific yoga training protocol which was administered not only helped to decrease blood pressure but also retard the progression of ceellular damage due to free radicals.     

Interaction of LDL and platelets in ischaemic and ischaemic risk subjects

Platelets play a vital role in the progression of atherosclerosis and thrombosis, a major cause of death worldwide. Platelets are activated by many triggers like elevated LDL in blood resulting in aggregation and formation of plaque. The purpose of this study was to investigate the effect of LDL and signal transduction inhibitor on the activation of platelets in Ischaemic risk subjects. Platelets from IHD and hyperlipidemic subjects were hypersensitive to ADP, as higher levels of platelet aggregation were observed in these groups. LDL from IHD hyperlipidemic subjects was more effective in activating platelets from any other group. Ox-LDL was more effective in activating platelets than native-LDL as monitored by level of platelet aggregation induced by PAF and thrombin. Calcium channel blocker, nifedipine and verapamil inhibited platelet aggregation at micromolar level. Protein kinase inhibitor, staurosporine was effective in inhibiting ADP induced aggregation at nanomolar level.     

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.     

Total antioxidant capacity and lipid peroxidation in liver transplantation

Liver transplantation is an accepted therapy for chronic liver disease patients. These patients generally have low levels of fat soluble vitamins, which have important antioxidant roles. Therefore, this study was undertaken to investigate whether such patients had evidence of antioxidant depletion and increased lipid peroxidation before transplant and whether the subsequent ischemia and reperfusion encountered during liver transplantation have any effect on antioxidant levels and lipid peroxidation. We assessed plasma total antioxidant capacity and serum lipid peroxide in 12 patients undergoing liver transplantation and equal numbers of healthy subjects. We found that before reperfusion, antioxidant levels were significantly decreased along with significantly elevated lipid peroxidation levels as compared with healthy controls (P<0.001). On reperfusion of the liver graft, further declined values of total antioxidant accompanied with highly elevated lipid peroxidation were seen than those of pre-reperfusion samples (P<0.001). This data shows that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Therefore antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.     

Proxidant and antioxidant status in patients of type II Diabetes Mellitus with IHD

Patients with type II Diabetes Mellitus (NIDDM) are more prone to Ischaemic Heart Disease (IHD). Although, oxygen free radicals are known to contribute to the development of IHD, conflicting reports are available regarding the antioxidant status in patients of NIDDM complicated with IHD. This study was undertaken to investigate the oxidative status in patients of NIDDM and to assess their correlation with plasma glucose, glycosylated haemoglobin and duration of diabetes. The levels of malondialdehyde were significantly increased where as levels of superoxide dismutase, Glutathione peroxidase and vitamin C were significantly decreased in diabetics without complications and non-diabetics with IHD when compared with the controls. The levels of malondialdehyde and Glutathione peroxidase were significantly increased where as levels of superoxide dismutase and vitamin C were significantly decreased in diabetics with IHD when compared with diabetics without complications and non-diabetics with IHD. The implications of the results are discussed.     

Association of Cholesteryl Ester Transfer Protein (CETP) Gene -629C/A Polymorphism with Angiographically Proven Atherosclerosis

Association of cholesteryl ester transfer protein (CETP) Gene -629C/A Polymorphism with angiographically proven atherosclerosis CETP gene has been linked to CAD risk via its role in HDL and LDL metabolism. There is no agreement of whether CETP is atherogenic or not. Furthermore, various genotypes of CETP gene have been associated with CETP levels and thus with atherosclerosis risk. Our aim was to study the association of CETP -629C/A gene polymorphism with CETP and HDL levels and their association if any with atherosclerosis. Study population consisted of angiographically documented 50 cases with coronary artery atherosclerosis and 50 controls negative for atherosclerosis of coronary artery. Serum lipid profile was measured on SYNCHRON CX-9 using standard kits. Serum CETP levels were measured by ELISA method. CETP -629C/A gene polymorphism was studied using PCR–RFLP method. There was no significant difference in lipid profile of the two groups. However, serum CETP level was significantly higher (46.44 ± 21.75 ng/ml) in cases than controls (37.10 ± 21.92 ng/ml) with p value =0.035. The frequency of -629A allele was higher (0.85) in cases than that of controls (0.81). Homozygosity of A allele was more in subjects with atherosclerosis of coronary artery. We conclude that CETP is atherogenic and could be used as atherogenic risk predictor in angiographically proven atherosclerosis. Also A allele of -629C/A polymorphism is more prevalent in cases; indicating its effect on expression of CETP gene.     

Role of ascorbic acid in human seminal plasma against the oxidative damage to the sperms

This study evaluated the extent of oxidative stress by measuring malondialdehyde and ascorbic acid in the seminal plasma of human subjects with different fertility potential. Semen samples from 148 subjects were evaluated (48 normozoospermics, 34 oligoasthenoteratozoospermics, 34 asthenoteratozoospermics and 32 azoospermics). malondialdehyde level was found to be significantly higher in the abnormal groups (oligoasthenoterato and asthenoterato-zoospermics) than normozoospermics (P < 0.01). Negative correlation was also found between malondialdehyde level, sperm concentration, sperm motility and sperm morphology. Level of ascorbic acid was found to be significantly higher in normozoospermics than other abnormal groups (P < 0.01). It was found to be correlated positively with all seminogram parameters and negatively with malondialdehyde level. The study revealed that, excess lipid peroxidation reflected by high malondialdehyde level with reduced ascorbic acid in human seminal plasma is associated with poor semen quality where as ascorbic acid content has positive correlation with fertility potential.     

Effect of glibenclamide,tolbutamide and insulin on serum lipoprotein cholesterol fractions in alloxan diabetic rabbits

The effects of administration of glibenclamide, tolbutamide and insulin on serum lipoprotein fractions in alloxan diabetic rabbits were studied with a view to understand the role played by these antidiabetic drugs to influence serum levels of these fractions. The elevated levels of cholesterol in serum lipoprotein fractions—HDL, LDL and VLDL in alloxan diabetic rabbits were found to be decreased significantly on treatment with glibenclamide, tolbutamide and insulin. However, the LDL-cholesterol: HDL-cholesterol ratio which is considered to be an atherogenic index showed a statistically significant increase in tolbutamide treated group and a statistically significant decrease in insulin-treated group, whereas the glibenclamide treated group showed no change.     

Study of genetic, metabolic and inflammatory risk factors in patients of acute ischemic stroke

Stroke is the third leading cause of death and foremost cause of disability. Based on studies in CAD patients, a focus has been shifted on genetic and inflammatory markers as risk factors for stroke besides deranged lipid profile. The present study was aimed to ascertain the role of Lipoprotein (a), C-Reactive protein (CRP) levels and lipids in patients of ischemic stroke. The study was done in 82 subjects including 40 Computerized Tomography (CT) proven patients of ischemic stroke and 42 age and sex matched controls. Complete biochemical parameters including lipid profile were carried out on autoanalyzer using standard kits and reagents. Lipoprotein (a) [Lp(a)] was determined by immunoturbidimetric assay. Atherogenic indices (Total cholesterol/ HDL, LDL/HDL and Lipid Tetrad Index) were calculated using these lipid parameters. The CRP levels were measured semi-quantitatively by latex agglutination test method. Out of 40 stroke patients, 38 had abnormalities in lipid profile (As per ATP III guidelines). A significant difference was seen in serum cholesterol, LDL cholesterol and atherogenic indices between the patients and controls. The difference in CRP levels in cases and control subjects was highly significant (4.78±0.72 mg/dl vs 0.76 ±0.70, p<0.001). 96.5% of patients with raised CRP had abnormal lipid levels also. CRP levels in stroke patients showed significant correlation with total cholesterol and LDL (p<0.001), Lp (a) (p=0.002) and atherogenic indices (p<0.05). Raised CRP levels in stroke patients were significantly associated with large territory infarcts, severe disability and poor functional outcome (p<0.05).Genetic [Lp(a)], metabolic (deranged Lipid profile) and inflammatory factors (CRP) together are instrumental in causing cerebrovascular arteriosclerosis leading to ischaemic stroke and can be used as important markers to identify patients at risk of severe stroke and to institute aggressive preventive strategies.     

Vitamin E supplementation on biochemical changes observed in agricultural field workers exposed to different classes of pesticides

A total of 41 healthy male pesticide sprayers exposed to different clases of pesticides for 3-5 years were compared with 21 controls matched for age and economic status with respect to free radical generation, lipid peroxidation, antioxidant status, cholesterol, lipoprotein status and haematological profile. Plasma lipid peroxidation was estimated in the form of thiobarbituric acid reactive substances (TBARS) produced. Significant increase in TBARS was observed in sprayers population when compared with control subjects and the level of TBARS increased with increase in the duration of exposure. The levels of antioxidants such as glutathione (GSH) were significantly depleted, whereas those of superoxide dismutase (SOD) were remarkably increased than control population. Significant reduction in total cholesetrol, alteration in lipoprotein fractions and nonsignificant changes in hematological parameters were observed. These results suggested that exposure to pesticidal residual drift augments the free radical generation, and lipid peroxidation. Decline in non-enzymatic antioxidant and elevation of enzymatic antioxidant were observed. Supplementation of α-tocopherol for 45 days resulted in the partial restoration of these biochemical changes produced by pesticides.     

Evaluation of Oxidative Stress and Antioxidant Status in Pregnant Anemic Women

The present study was conducted to investigate the oxidant–antioxidant status in iron deficient pregnant anemic women. One hundred thirty pregnant women with iron deficiency anemia (IDA) were divided into three groups, namely mild (50), moderate (50) and severe (30) anemic along with pregnant healthy women as controls (50). The complete blood count, plasma lipid peroxidation products, enzymatic and non-enzymatic antioxidants were measured according to respective protocols. The levels of complete blood count, iron, ferritin along with antioxidant enzymes namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly reduced in all IDA groups. However, the level of oxidized glutathione, lipid peroxides, protein carbonyls, conjugated dienes were found significantly increased in all anemic patients. Antioxidant vitamins, namely C, E and A were also found significantly decreased in IDA patients. On the basis of our results, it may be concluded that IDA tends to increase the pro-oxidant components, which may result in various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.     

Protective influence of vitamin E on the antioxidant defence system in the whole blood and liver of normal and alloxan-induced diabetic rats

The effect of oral administration of vitamin E for twenty-eight consecutive days on blood glucose, reduced glutathione levels, antioxidant enzymes (superoxide dismutase and catalase activities), and levels of malondialdehyde (as an index of free radical-mediated lipid peroxidation) was observed in the whole blood and liver of normal and alloxan-induced diabetic rats. It was found that oral administration of vitamin E significantly (p<0.05) lowered the blood glucose level and increased the body weight of the diabetic rats. The activities of superoxide dismutase and levels of reduced glutathione increased significantly (p<0.05) while the level of lipid peroxidation decreased.     

Oxidative stress and antioxidant status in patients with chronic myeloid leukemia

Chronic myeloid leukemia is a myeloproliferative disorder with a unique rearrangement, the Philadelphia chromosome. Oxidative stress, a pervasive condition of an increased number of reactive oxygen species, is now recognized to be prominent feature of various diseases and their progression. Thus antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall true state of health. The relationship between antioxidants status and levels of well-known markers of oxidative stress that are measured as lipid peroxides and oxidized proteins reflect better health indices and postures. The aim of this study was to evaluate the role of oxidative stress in pathophysiology of Chronic myeloid leukemia by measuring the circulating plasma lipid peroxide levels in terms of malonyldialdehyde, total lipid hydroperoxide and oxidized proteins as protein carbonyl whereas antioxidant status were estimated in terms of reduced glutathione and total thiol in plasma of Chronic myeloid leukemia patients. The present study included 47 Chronic myeloid leukemia patients and 20 age-and sex-matched healthy subjects. Out of 47 Chronic myeloid leukemia patients, 31 were in chronic phase (CML-CP) and 16 in accelerated phase (CML-AP). The median age of Chronic myeloid leukemia patients was 33 years and that of controls was 32 years. Oxidative stress and antioxidant status in plasma were evaluated by spectrophotometric procedures. There was a significant increase (p<0.05) in plasma malonyldialdehyde, total lipid hydroperoxide and protein carbonyl levels in Chronic myeloid leukemia patients as compared to healthy subjects. Our results also showed that plasma malonyldialdehyde and protein carbonyl levels were markedly elevated (p<0.05) in both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy volunteers. Antioxidant status was found to be significantly decreased (p<0.05) in Chronic myeloid leukemia patients and its phases as compared to healthy participants. It could be concluded that oxidative stress may be associated with the pathophysiology of Chronic myeloid leukemia.     

A clinical study on cortisol and certain metabolites in some chronic psychosomatic disorders

Present clinical study involved two groups of psychosomatic disorders, bronchial asthma and rheumatoid arthritis. In the study, the levels of plasma cortisol, blood glucose, total cholesterol and triglycerides were estimated in 125 clinical subjects, (50 normal controls, and 40 having bronchial asthma and 35 suffering from rheumatoid arthritis. The results showed a significant change in the levels of plasma cortisol and blood glucose in both the stressed clinical groups' vis-à-vis normal controls. The levels of atherogenic lipids (total cholesterol and triglycerides) were found quite elevated in both the diseased groups. However, in rheumatoid arthritis, the physiological changes were relatively more pronounced. The findings of this study indicate that rheumatoid arthritis is a relatively more chronic and late onset disorder as the functional performance of hypothalamopituitary-adrenocortical axis gradually declines with passage of time and the ability of the adrenocortical response to return to normalcy becomes impaired.     

Role of Oxidative Stress in Various Stages of Psoriasis

Psoriasis is a chronic inflammatory, proliferative skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. It is associated with a number of biochemical and immunological disturbances. Recently, it has been suggested that increased reactive oxygen species (ROS) production and compromised function of antioxidant system may be involved in the pathogenesis of this disease. In the present study, 90 psoriasis patients were selected. Disease severity was assessed by psoriasis area severity index score and grouped as mild, moderate and severe (each group consists of 30 subjects) and compared with 30 healthy controls. Serum levels of malondialdehyde, nitric oxide end products and the activities of antioxidant enzymes such as erythrocyte-superoxide dismutase, catalase and total antioxidant status were investigated in these groups/subjects. As compared to controls, we found severitywise significantly increased serum malondialdehyde, nitric oxide end products with decrease in erythrocyte-superoxide dismutase activity, catalase activity and total antioxidant status in patients with psoriasis suggesting worsening of the disease. It seems to be linked with the enhancement of Reactive Oxygen Species production and decreased antioxidant potential in psoriasis.     

Study on Impact of Iron and Folic Acid on the Plasma Trace Minerals in Pregnant Anemic Women

Iron deficiency anemia is one of the causes that lead to significant mortality and morbidity among pregnant women and fetus. The present study was undertaken to explore oral iron supplementation can modify the metal contents in pregnant anemic women. Iron and folic acid supplementations was given to 500 anemic women (mild = 200, moderate = 200, and severe = 100) and 100 age matched non-anemic controls daily for 100 days. Blood index values and plasma trace minerals were estimated as per standard protocols. Haemoglobin and ferritin levels were found significantly increased (p < 0.001) in anemic and control subjects after treatment. Moreover, the serum transferring receptor levels and total iron binding capacity were found significantly decreased in all treated groups. Iron (Fe), zinc (Zn) and copper (Cu) levels were found increased (p < 0.01) after oral iron supplementation groups. Moreover, selenium (Se) manganese (Mn) and were found to be decreased in all treated groups. Data provides the conclusion that iron and folic acid supplementation recovered the essential trace minerals, except manganese, which may lead to various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.     

Comparative account of serum lipids,lipoproteins and apolipoprotein-B in patients of coronary artery disease

Serum total lipids (cholesterol and triglyceride), lipoproteins (VLDL, LDL and HDL) and Apolipoprotein-B levels of normal healthy individuals (n=25) and coronary artery disease patients (n=25) were estimated. The objective of the present study was to ascertain the role of apo-B in causation and inheritance of coronary artery disease. It was observed that on an average serum total cholesterol and triglyceride more than 200 mg/dl bring the individuals to a risk of coronary artery disease (CAD) irrespective of the age. CAD patients achieved this value at an early age (35–45 years). Similarly VLDL and LDL levels were found to be significantly raised in CAD patients when compared to that of age matched normal individuals, with patients achieving risk values at an early age. HDL levels were found to be significantly lower in CAD patients as compared to normal individuals. Serum apo-B levels were significantly raised in CAD patients as compared to age matched normal individuals. Patients with positive family history of CAD had raised serum apo-B levels than those having negative family history. A positive coefficient of correlation was observed between serum apo-B and LDL levels suggesting that more the number of Apo-B particles, more will be the synthesis of atherogenic particle (LDL). Patients with negative family history had serum apo-B levels closer to those of normal individuals and in these individuals HDL levels were found to be significantly lowered, suggesting that loss of scavenger role of HDL could be the risk factor responsible for the causation of CAD in these patients, with negative family history of coronary artery disease.     

Serum Lipid Alterations in Early Rheumatoid Arthritis Patients on Disease Modifying Anti Rheumatoid Therapy

Dyslipidaemia is a major CVD risk factor in the general population. Current evidence suggests that lipid metabolism is altered in RA due to inflammation, and that use of anti-inflammatory therapy may reverse some of these changes. The objective of our study is to compare the effect of treatment with DMARD on lipid fractions after 6 months of therapy. Forty patients who met the American College of Rheumatology, ACR/EULAR criteria for rheumatoid arthritis, with disease duration of less than 1 year and no prior treatment were included in the study. Thirty healthy volunteers were included as controls. The mean DAS-28 at disease onset was 5.15 ± 1.3. Early Rheumatoid Arthritis (ERA) patients exhibited higher serum levels of total cholesterol (TC) and lowdensity lipoprotein cholesterol (LDL-C) and lower serum high-density lipoprotein cholesterol (HDL-C) levels compared to controls. As a consequence, the atherogenic index of plasma [log (TG/HDL-C)], the atherogenic indices: TC/HDL-C as well as LDLC/HDL-C was significantly higher in ERA patients compared to controls. After 6 months of treatment, there was significant reduction of the DAS 28, HDL-C and Apo A-I improved and Lp(a) decreased significantly. All lipid ratios improved, a phenomenon primarily due to the increase in serum HDL-C levels. These changes were inversely correlated with CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves with DMARD therapy.