Oxidative stress in cases of chronic fluoride intoxication

This study was conducted to find out the level of oxidative stress and effect of supplementation of vitamin C, D and Calcium on levels of SOD, serum and urinary fluoride in children residing in endemic fluorosis area. For this the fluoride belt of Jaipur district was selected. The parameters selected were Super oxide dismutase, serum fluoride and urinary fluoride. The study was conducted on one hundred children, selected from four areas (25 from each area) consuming water containing 1.2, 2.4, 5.6 and 13.6 mg/l of fluoride. Drinking water fluoride, serum and urinary fluoride were measured by Ion selective electrode method. Serum SOD by Xanthine oxidase method using kit of Ransod (kit cat. No. SD125). The post treatment values showed a significant reduction in serum fluoride and SOD. Urinary fluoride levels increased significantly in post treatment stage. The results revealed a normal SOD levels in all groups but an increasing trend was observed with increasing fluoride concentration. Treatment with Calcium, Vitamin D and Vitamin C showed a significant reduction in serum fluoride and SOD and increase in urinary fluoride. A high positive correlation between pretreatment and post treatment group was observed in serum fluoride, SOD and urinary fluoride (P < 0.05). The study indicated an increasing oxidative stress in cases of fluorosis with increasing drinking water fluoride concentration. Treatment with Calcium, Vitamin D and Vitamin C resulted a significant reduction in serum fluoride and SOD and increase in urinary fluoride.     

Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics

A disturbance in the antioxidant defense system including α-tocopherol, ascorbic acid and reduced glutahtione metabolism due to free radical induced oxidative injury has been implicated in various neuro-psychiatric disorders. The roles of these antioxidants, changes in their blood levels and correlation with oxidative stress were studied in a common psychiatric illness Schizophrenia. Fifty-eight subjects of either sex ranging in age from 18–60 years divided into two age groups (≤40 and >40 years) diagnosed for schizophrenia, and forty age and sex-matched normal subjects as controls were included in the study. Blood samples were analyzed for malondialdehyde (MDA), α-tocopherol, total ascorbic acid (TAA), dehydro ascorbic acid (DHAA), reduced ascorbic acid (RAA), leucocyte ascorbic acid (LAA) and reduced glutathione (GSH). A decrease in the levels of α-tocopherol, total ascorbic acid and reduced glutathione was found in schizophrenics compared to normal controls. Further a significant rise in oxidative stress and decreased antioxidant status was observed in the chronic stage of schizophrenia as compared to those in acute condition. A significant rise in dehydroascorbic acid with concomitant fall in reduced ascorbic acid suggests scavenging action of ascorbic acid and its utilization with increased oxidative stress as indicated by high blood malondialdehyde levels. Leucocyte ascorbic acid, a better index of ascorbic acid status was also found to be reduced in schizophrenics, suggesting depletion of body stores of ascorbic acid and the condition worsened with advancing age.     

Parathyroid and Calcium Status in Patients with Thalassemia

Thirty patients with thalassemia major receiving repeated blood transfusion were studied to see their serum parathyroid hormone (PTH) and calcium status. Serum PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were determined. Half of these patients, in addition to transfusion, were also supplemented with vitamin D (60,000 IU for 10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h urinary calcium concentrations of the patients receiving transfusions were found to be significantly reduced while their serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were not significantly altered when compared to the respective mean values for the control group. Vitamin D and calcium supplementation significantly increased their serum PTH and calcium levels. Supplementations also increased urinary excretion of calcium. The results thus suggest that patients with thalassemia have hypoparathyroidism and reduced serum calcium concentrations that in turn were improved with vitamin D and calcium supplementation.     

Antioxidant status and peroxidative stress in mother and newborn —A pilot study

Serum antioxidant status and peroxidative stress was estimated in 30 pregnant women, their newborn infants and 25 non-pregnant women. Serum Ascorbic acid, α-tocopherol, retinol & β-carotene levels were found to be significantly reduced and peroxidative stress was significantly higher in mothers as compared to matched non-pregnant women. Newborn had significantly higher levels of ascorbic acid as compared to their mother but had significantly lower levels of lipid soluble vitamins. The peroxidative stress in newborn was found to be significantly less as compared to their mothers. A positive correlation of ascorbic acid and α-tocopherol levels between mother and newborn reflects that their status in mother does influence the newborn status.     

Validating a High Performance Liquid Chromatography-Ion Chromatography (HPLC-IC) Method with Conductivity Detection After Chemical Suppression for Water Fluoride Estimation

Abstract A variety of methods, including the Ion Selective Electrode (ISE), have been used for estimation of fluoride levels in drinking water. But as these methods suffer many drawbacks, the newer method of IC has replaced many of these methods. The study aimed at (1) validating IC for estimation of fluoride levels in drinking water and (2) to assess drinking water fluoride levels of villages in and around Vellore district using IC. Forty nine paired drinking water samples were measured using ISE and IC method (Metrohm). Water samples from 165 randomly selected villages in and around Vellore district were collected for fluoride estimation over 1 year. Standardization of IC method showed good within run precision, linearity and coefficient of variance with correlation coefficient R² = 0.998. The limit of detection was 0.027 ppm and limit of quantification was 0.083 ppm. Among 165 villages, 46.1% of the villages recorded water fluoride levels >1.00 ppm from which 19.4% had levels ranging from 1 to 1.5 ppm, 10.9% had recorded levels 1.5–2 ppm and about 12.7% had levels of 2.0–3.0 ppm. Three percent of villages had more than 3.0 ppm fluoride in the water tested. Most (44.42%) of these villages belonged to Jolarpet taluk with moderate to high (0.86–3.56 ppm) water fluoride levels. Ion Chromatography method has been validated and is therefore a reliable method in assessment of fluoride levels in the drinking water. While the residents of Jolarpet taluk (Vellore distict) are found to be at a high risk of developing dental and skeletal fluorosis.     

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.     

Biochemical Effects of Lead Exposure on Battery Manufacture Workers with Reference to Blood Pressure, Calcium Metabolism and Bone Mineral Density

Lead is one of the most widely scattered toxic metals in the environment and used by mankind for over 9,000 years. Lead in the environment may be derived from natural or anthropogenic sources. In humans, lead can cause a wide range of biological effects depending upon the level and duration of exposure. The purpose of this study was to find out the effect of lead exposure on systolic and diastolic blood pressure, serum calcium, ionized calcium, phosphorus, parathyroid hormone and vitamin D and examine the overall effect of all these parameters on the bone mineral density of battery manufacture workers. For this study ninety battery manufacture workers were selected and divided in three groups depending upon duration of lead exposure. Group I—workers with duration of lead exposure 1–5 years, Group II—workers with duration of lead exposure 6–10 years and Group III—workers with duration of lead exposure more than 10 years. Each group consisted of thirty workers. Thirty age matched healthy control subjects were taken for comparison. Demographic, occupational and clinical data were collected by using questionnaire and interview. The venous blood samples were collected from the study groups and normal healthy control group. At the time of blood collection random urine samples were collected in amber coloured bottles. The biochemical parameters were estimated by using standard assay procedures. Statistical analysis of the data was done using independent student‘t’ test for parametric variables. Values were expressed as mean ± standard deviation (SD). P values of 0.05 or less were considered to be statistically significant. The blood lead levels and urinary lead levels of all workers were significantly increased (P < 0.001) in proportion to the duration of lead exposure as compared to controls. Systolic and diastolic blood pressure were significantly raised (P < 0.001) in all three study groups of battery manufacture workers as compared to controls. Serum Calcium, Ionized calcium, phosphorus were significantly decreased (P < 0.001) in all the three study groups. Serum vitamin D levels were lowered (P < 0.01) and serum PTH was increased (P < 0.01) in workers as compared to controls. The results of this study clearly indicate that the absorption of lead is more in these workers which adversely affects blood pressure, disturbs calcium and phosphorus metabolism which further impairs mineralization of bone resulting in decreased bone mineral density observed in these workers. Lead toxicity is still persistent in battery manufacture workers though they are using sophisticated techniques in these industries. There is a need to protect the workers from the health hazards of occupational lead exposure.     

Effect of folic acid and vitamin B<Subscript>12</Subscript> administration on phenytoin induced toxicity in rats

Folic acid and vitamin B₁₂ are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B₁₂ on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated. The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as indices of biochemical changes. The ingestion of phenytoin alone in rats significantly reduced serum protein while AST, ALT activities incresed as compared to the control (P<0.05). Supplementation of phenytoin with oral administration of 70microgram/kg body wt of folic acid resulted in a significant reversal in serum total protein and suppression in serum AST and ALT activities. Vitamin B₁₂ supplementation did not afford any significant protection against the effect of phenytoin ingestion but rather phenytoin toxicity was exacerbated in this study. However, the combined effects of vitamin B₁₂ and folic acid ameliorated the effects of phenytoin on serum enzymes of experimental rats. The effect of combination of phenytoin with folic acid or folic acid and vitamin B₁₂ is an interesting finding. Supplementation of phenytoin with folic acid or combination of these vitamins may be recommended for the purpose of ameliorating the adverse biochemical changes which are associated with phenytoin therapy. Further work is ongoing to help elucidate the effects of phenytoin and these vitamins on oxidative stress inducing mechanism.     

Reduced plasma ascorbic acid and red cell glutathione contents in sickle cell disease—A preliminary report

Glutathione and ascorbic acid in erythrocytes are suggested to be essential in the detoxification of superoxide radicals and hydrogen peroxide formed during red cell metabolism. In sickle cell patients who are more prone to haemolysis have greater propensity for the formation of superoxide radical and hydrogen peroxide. In the present study conducted on sickle cell patients provide evidence for the presence of reduced levels of both ascorbic acid and glutathione in the red cells. This may seem to suggest that vitamin C supplementation may help such patients who are prone to haemolysis.     

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T₃, T₄, TSH, Liver and Kidney Function tests were analysed using standard kits. Forty-six hypothyroid patients were re-evaluated 6 weeks after thyroxine substitution therapy. Hypothyroid subjects (n=80) showed significantly raised serum creatinine and uric acid levels as compared to euthyroid subjects (n=96). After 6 weeks of thyroxine replacement, serum creatinine and uric acid decreased significantly and were comparable to euthyroid group. A positive correlation of ALT, AST, uric acid, protein and albumin with TSH levels (p<0.05) and negative correlation of serum T₄ levels with ALT, AST, proteins (p<0.05) was observed in the hypothyroid group. Hypothyroidism results in reversible impairment of hepatorenal function.     

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.     

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.     

Serum creatine phosphokinase in thyroid disorders

The decreased serum levels of triiodothyroinine (T3) and thyroxine (T4) in hypothyroid patients is well established but whether there is any correlation of creatinephosphokinase (CPK) with hypothyroidism is not well established. There is a paucity of reference on this study. Therefore a study of serum CPK and thyroid profile was carried out in thyroid diseases. In hypothyroid patients T3, T4 levels in serum were found to be lowered with an increase level of thyroid stimulating hormone (TSH) associated with marked rise in serum CPK level. In hyperthyroid patients serum levels of T3, T4 were found to be increased with decrease in TSh with significant decrease in creatine phosphokinase level. Serum creatine phosphokinase levels thus show an inverse relation with serum T3, T4 levels.     

Evaluation of the changes in serum iron levels in pre-eclampsia

Serum iron levels were studied in 50 patients with pre-eclampsia and the results were compared with 50 control cases. Their serum iron levels were found to be higher than the controls. Increase in serum iron was directly proportional to the increased levels of uric acid, urea and creatinine. Mean reticulocyte counts, plasma free haemoglobin and unconjugated bilirubin levels were also higher in these patients. It is suggested that haemolysis may be a major contributory factor for the increased levels of serum iron in pre-eclampsia.     

Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis and Vitamin D in Hemodialysis Patients: Relation to Carotid Intima-Media Thickness

Cardiovascular disease, as the leading cause of patient death with chronic kidney disease, could be predicted by carotid atherosclerosis. The aim of the present study was to evaluate a possible relationship between serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Vitamin D levels with mean right/left carotid intima-media thickness (cIMT), in the hemodialysis (HD) patients. In this cross-sectional study, serums were obtained from 50 stable chronic HD patients and 39 healthy controls. The serum levels of sTWEAK, Vitamin D, intact parathyroid hormone (iPTH) in both groups, and cIMT were determined in HD patients by standard methods. Serum levels of sTWEAK were higher [808.8 (521.6–5032.4) pg/ml vs. 664.4 (487.4–2955.8) pg/ml (p = 0.006)] and Vitamin D levels were lower [13.4 (2.5–153) ng/ml vs. 27.8 (18.4–59.0) ng/ml (p = 0.001)] in the hemodialysis patients than in the healthy control. No important correlation was found between sTWEAK Vitamin D levels (r = 0.010/p = 0.946), and mean right(r = ?0.194/p = 0.178) and left (r = 0.061/p = 0.673) cIMT in the HD patients. Our study shows that sTWEAK levels are elevated in HD patients. This elevation has no association with the cIMT.     

Correlative study of fluoride content in urine,serum and urinary calculi

Fluoride content was measured in 100 urinary stones retrieved by open surgery of stone formers admitted at PGIMS Rohtak and their respective urine and serum and compared with those of healthy individuals. The concentration of fluoride was also measured in the sources of drinking water of these stone formers. The concentration of fluoride was definitely significantly higher in serum (p>0.01) and highly significantly higher in urine (p>−0.001) of stone formers compared to those of healthy individuals. The content of oxalate in serum and 24 h urine of the stone formers was also measured, which was increased significantly (p<0.005 and p<0.001) compared to healthy individuals. The concentration of fluoride was probably significantly higher in drinking water of these stone formers than the normal ones. There was a positive correlation between the content of fluoride of urinary stones and urine of stone patients (r=.88); stone and serum (r=.62); drinking water and stone (r=.85) and their urine and serum (r=.54); urine and drinking water (r=.83) and serum and water (r=.51). These results indicate a definite role of fluoride in urinary stone formation.     

Circadian Periodicity of Circulating Plasma Lipid Peroxides,Uric Acid and Ascorbic Acid in Renal Stone Formers

Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20–60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21–45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90 ± 0.03 vs. 2.28 ± 0.06; F = 94.929, p < 0.001), a lower MESOR of serum ascorbic acid (0.722 ± 0.010 vs. 0.839 ± 0.10; F = 32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient’s response to treatment for further management.     

Serum lipids, lipoproteins and sex-hormone binding globulin in breast cancer

Serum levels of various lipid parameters, i.e., triglycerides, total cholesterol, alpha lipoprotein or high density lipoprotein (HDL)-cholesterol and beta lipoprotein or low density lipoprotein (LDL)-cholesterol were measured in a total of 138 histologically proven cases of breast cancer along with 146 control women. The mean levels of serum triglycerides, total cholesterol and LDL-cholesterol were found to be significantly higher in breast cancer cases as compared to controls. However, lower mean levels of serum HDL-cholesterol and sex-hormone binding glubulin (SHBG) were observed in breast cancer patients than the control subjects. The results indicate a probable relation between serum lipids and the activity of sex-hormones. Moreover, the study reflects an overall disturbance of lipid metabolism in the pathological process of breast cancer.     

Association of Obesity with Hormonal Imbalance in Infertility: A Cross-Sectional Study in North Indian Women

Hormones play an important role in the development and regulation of reproductive function and the menstrual cycle of women. Extremes of body weight tend to affect the homeostasis of the hypothalamo–pituitary–gonadal axis. This cross-sectional study was carried out in 113 women (57 with primary infertility and 56 with secondary infertility) in the age group 20–35 years, presenting for hormonal evaluation of infertility in a tertiary care hospital. After preliminary clinical evaluation, anthropometric indices (height, weight, BMI, waist circumference and waist hip ratio) were measured in all subjects. Fasting blood sample drawn on second/third day of menstrual cycle was analysed for serum luteinizing hormone, follicle stimulating hormone (FSH), prolactin and thyroid stimulating hormone (TSH). Serum FSH levels showed a significant positive correlation with indicators of central obesity (waist circumference and waist hip ratio in both the study groups). In primary infertility, significant positive correlation was also observed between serum FSH levels and other markers of obesity like body weight, hip circumference and BMI. In secondary infertility, serum prolactin and serum TSH levels demonstrated a significant positive correlation with body weight and BMI. Obesity is associated with hormonal derangements which are responsible for infertility. In overweight women with infertility, weight loss should be considered as a first line treatment.     

Serum glycoconjugates and ceruloplasmin in cancer of uterine cervix

The present study was done to assess the levels of glycoconjugates and ceruloplasmin in sera of patients with cervical cancer. Serum hexoses, hexosamines, sialic acid and fucose are elevated in a variety of inflammatory and neoplastic conditions. All the glycoconjugates, except fucose were increased in serum of patients compared to controls. Also, hexoses and sialic acid levels were high in patients with later stages of cancer compared to patients with early stage disease (P=<0.0001, P=0.03). Serum ceruloplasmin was increased in patients with early stage cancer (51.5mg/dl) and with late stage cancer (61mg/dl) compared to controls (38mg/dl). The elevated glycoconjugates may be the result of inflammatory reaction associated with neoplasia, as serum ceruloplasmin (an acute phase reactant) is also increased in these patients.