Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol.

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0-21 µg/ml) for 6, 12, and 24 h, and in combination with curcumin (9.2 µg/ml) or α-tocopherol (4.3 µg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p < 0.05). The results of the present study provide experimental evidence of involvement of oxidative stress in propoxur-mediated genotoxicity in human PBMC and highlight the antioxidant role of curcumin and α-tocopherol following propoxur exposure.

Assessment of urinary cotinine levels in women with gynecological complaints at a tertiary care hospital: A pilot study.

Gynecological effects due to smokeless tobacco exposure are not well studied. This cross-sectional study was undertaken with the objective to evaluate the urinary cotinine levels in women of reproductive age with gynecological complaints. The study was conducted in 2015 at the outpatient clinic of the Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi. A total of 192 consecutive women presenting with gynecological complaints (pelvic inflammatory disease (PID), infertility, and menstrual abnormality) were recruited. Their demographic details and tobacco exposure were recorded. All of them denied exposure to any form of tobacco. Urinary cotinine level of each participant was measured. The mean urinary cotinine level was 23.60 ± 12.00 ng/ml. PID was the most common gynecological complaint. Women with PID had significantly higher urinary cotinine levels compared to those with menstrual complaints and infertility: 24.9548 (±12.259) ng/ml versus 20.2042 (±10.9248) ng/ml. This study highlights the importance of addressing the issue of secondhand smoke exposure and reproductive morbidities in women.

Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.

Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.

Association of organochlorine pesticides with the mRNA expression of tumour necrosis factor-alpha (TNF-α) & cyclooxygenase-2 (COX-2) genes in idiopathic preterm birth.

BACKGROUND & OBJECTIVES: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in preterm delivery (PTD) cases. METHODS: Maternal blood samples of PTD (n=30) cases and equal number of term delivery (n=30) were collected at the time of labour. Women occupationally exposed to OCPs and other high risk factors such as anaemia, hypertension, bacterial vaginosis, renal and heart disease, diabetes, etc. were excluded. The OCP levels were estimated by gas chromatography, and mRNA expressions of TNF-α and COX-2 genes were analysed using real-time PCR (qPCR). RESULTS: Significantly higher levels of ß-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, p0 =0.001), p'p'-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, p0 =0.003), and o'p'-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. l0 inear positive correlations were observed between period of gestation (POG) and ΔCt of COX-2 and TNF-α genes. INTERPRETATION & CONCLUSIONS: Environmental factors such as OCPs may be associated with inflammatory events showing gene-environment interaction in PTB cases. Evaluating the molecular control of inflammation along with gene environment interaction may be used as a model to explore the aetiology of idiopathic PTB cases and may be considered for the prognosis of adverse reproductive outcomes.

Idiopathic Fetal Growth Restriction: Repercussion of Modulation in Oxidative Stress.

Oxidative stress has been proposed as one of the causes involved in idiopathic fetal growth restriction (IFGR). However, the exact relationship between oxidative stress and IFGR is not understood. This study aimed at understanding the role of oxidative stress and antioxidant status in IFGR materno-fetal dyads and matched controls. 75 materno-fetal dyads with IFGR were enrolled with equal number of normal low risk controls. Malondialdehyde (MDA) levels were measured as marker of oxidative stress, while paraoxonase-1 (PON1) activity and total antioxidant capacity (TAC) of serum were measured as markers of antioxidant status. MDA levels were increased in both maternal and cord blood of IFGR neonates as compared to controls (p < 0.001). TAC of serum were found to be decreased in IFGR (both maternal and cord blood) as compared to controls (p < 0.001; p < 0.05, respectively). PON1 activity was found to be decreased in the IFGR mothers while it was found increased in IFGR cord blood (p < 0.01; p < 0.001)). IFGR is a state of increased oxidative stress. Decreased PON1 enzymatic activity in mothers is also associated with IFGR.

Organochlorine pesticide levels in maternal blood and placental tissue with reference to preterm birth: a recent trend in North Indian population.

Organochlorine pesticides (OCPs) have been widely used in public health and agriculture programs in developed as well as developing countries, including India. Being xenoestrogenic in nature, OCPs may act as endocrine disruptors leading to preterm birth (PTB) through disturbance of normal estrogen-progesterone ratio. PTB is the leading cause of neonatal deaths worldwide. Therefore, the present study is aimed to determine the extent to which persistent environmental chemicals may accumulate in pregnant women and placenta and ascertain possible associations between exposure level and period of gestation (POG), baby weight, and/or placental weight in PTB cases. Maternal blood and placenta samples of PTB cases (n = 50) and subjects of term delivery as controls (n = 50) were collected. OCP residue levels were estimated by the gas chromatography system equipped with an electron capture detector. Significantly higher levels of α-hexachlorocyclohexane (α-HCH), ß-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethane (DDD), and dichlorodiphenyldichloroethylene (DDE) were found in maternal blood of PTB cases as compared to control. Significantly higher levels of DDE and dichlorodiphenyltrichloroethane (DDT) were also found in placental tissue of PTB cases as compared to control group. There was a statistically significant negative correlation between maternal blood level of α-HCH and birth-weight (r = -0.299) and POG (r = -0.234). γ-Hexachlorocyclohexane (γ-HCH) and dieldrin had a negative correlation with placental weight (r = -0.401 and -0.256, respectively), and DDE and ß-HCH had a negative correlation with POG (r = -0.251 and -0.229, respectively). The presence of OCPs in maternal blood and placental tissue represents prenatal exposure hazard for fetuses due to chronic bioaccumulation and poor elimination with possible deleterious effect on health.

Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population.

OBJECTIVES: It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. METHODS: This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. RESULTS: We found a statistically significant association between AD and high levels of ß-hexachlorocyclohexane (ß-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION: This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with ß-HCH, dieldrin, and copper to influence the risk of AD.

Gene-environment interaction in preterm delivery with special reference to organochlorine pesticides.

We investigated the association between glutathione S-transferases mu1 (GSTM1), theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs) level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected at the time of delivery/after delivery. Women occupationally exposed to OCPs and other high-risk factors such as anemia, hypertension and dietary habit were excluded. The OCP levels were estimated by gas chromatography, and polymorphic analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and PCR-restriction fragment length polymorphism, respectively. The frequency of GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the controls. Significantly high levels of α-hexachlorocyclohexane (HCH), γ-HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane and p'p'-DDE were found in the cord blood of PTD cases compared with the controls. A significant association was seen between ß-HCH and GSTM1 genotype when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and period of gestation (POG) was ascertained. A significant reduction in POG was observed. Similarly, cord blood dieldrin levels were significantly associated with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that higher levels of OCPs in pregnant women may be associated with increased risk of 'idiopathic' PTD. Furthermore, this study shows that the interaction between high OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the risk of PTD, thus providing evidence for a gene-environment interaction in pregnant women.

Salivary progesterone as a biochemical marker to predict early preterm birth in asymptomatic high-risk women.

OBJECTIVE: To evaluate salivary progesterone as a predictor of early preterm birth (PTB) and compare it with transvaginal sonographic (TVS) cervical length in asymptomatic high-risk women. DESIGN: Prospective study. SETTING: Departments of Obstetrics and Gynaecology and Biochemistry at UCMS & GTBH, Delhi, India. SAMPLE: Ninety pregnant women. METHODS: The progesterone concentration in saliva of asymptomatic pregnant women at high risk for preterm delivery was estimated by immunoassay, and cervical length was measured by TVS, at the first antenatal visit at 24-28 weeks of gestation, and then repeated 3-4 weeks later. MAIN OUTCOME MEASURES: Early PTB, mean and critical cut-off values of salivary progesterone, and a diagnostic value comparison of salivary progesterone with TVS cervical length. RESULTS: The mean value of salivary progesterone was significantly lower in all women who delivered at <37 weeks of gestation (n = 38), compared with the term group (n = 52; P < 0.001). Salivary progesterone decreased significantly from the first to the second visit, with the maximum decrease observed in women who delivered at <34 weeks of gestation (29.6%, 95% CI 17.8-41.4%, P < 0.002). The single predictive critical cut-off value for salivary progesterone was 2575 pg/ml, below which more than 80% of women delivered prematurely before 34 weeks of gestation, with sensitivity, specificity, and positive and negative predictive values of 83% (95% CI 58.6-96.4%), 86% (95% CI 75.9-93.1%), 60% (95% CI 38.6-78.8%) and 95% (95% CI 87.1-99.0%), respectively. The TVS cervical length decreased significantly (P < 0.001) in the women who delivered prematurely. CONCLUSIONS: Low salivary progesterone concentration can be used for predicting early PTB in asymptomatic high-risk women.

Assessment of oxidative stress markers and concentrations of selected elements in the leaves of Cassia occidentalis growing wild on a coal fly ash basin.

Assessment of oxidative stress levels and tissue concentrations of elements in plants growing wild on fly ash basins is critical for realistic hazard identification of fly ash disposal areas. Hitherto, levels of oxidative stress markers in plants growing wild on fly ash basins have not been adequately investigated. We report here concentrations of selected metal and metalloid elements and levels of oxidative stress markers in leaves of Cassia occidentalis growing wild on a fly ash basin (Badarpur Thermal Power Station site) and a reference site (Garhi Mandu Van site). Plants growing on the fly ash basin had significantly high foliar concentration of As, Ni, Pb and Se and low foliar concentration of Mn and Fe compared to the plants growing on the reference site. The plants inhabiting the fly ash basin showed signs of oxidative stress and had elevated levels of lipid peroxidation, electrolyte leakage from cells and low levels of chlorophyll a and total carotenoids compared to plants growing at the reference site. The levels of both protein thiols and nonprotein thiols were elevated in plants growing on the fly ash basin compared to plants growing on the reference site. However, no differences were observed in the levels of cysteine, reduced glutathione and oxidized glutathione in plants growing at both the sites. Our study suggests that: (1) fly ash triggers oxidative stress responses in plants growing wild on fly ash basin, and (2) elevated levels of protein thiols and nonprotein thiols may have a role in protecting the plants from environmental stress.

Prevalence and predictors of adverse outcomes in neonatal seizures.

OBJECTIVES: Neonatal seizures are significant cause of neonatal mortality and morbidity. Current study was planned to study prevalence of adverse outcomes in neonatal seizures and identify its predictors. METHODS: This observational descriptive study was carried out on 220 neonates with seizures. Neonates who succumbed to illness/ death before investigations, or whose maternal records were incomplete were excluded. Blood sugar, serum calcium, serum electrolytes, and USG skull were done in all patients. CT scan, MRI and inborn errors of metabolism profile were done as and when indicated. Adverse outcomes were defined as death, phenobarbitone non responders, or abnormal examination at discharge. Antenatal, perinatal and neonatal predictors of adverse outcomes in neonatal seizures were evaluated. RESULTS: Out of 220 neonates with seizures 76(34.5%) had adverse outcomes. Very low birth weight babies (≤1500 gm) [OR 1.27(CI 0.57-2.84)], microcephaly [OR 5.93 (CI 0.55-64.41)], Apgar score≤3 at 5 minutes [OR 11.28(CI 14.18-30.45)], seizure onset within 24 hours [OR 5.99(CI 12.43-14.78)], meningitis [OR 2.63(CI 0.08-6.39)], septicemia [OR1.22(CI 0.45-3.31)] and abnormal cranial USG [OR 7.95(CI 12.61-24.22)] were significant predictors of adverse outcomes in neonates with seizures. CONCLUSION: Prematurity, very low birth weight, birth asphyxia, meningitis, septicemia and abnormal USG could predict adverse outcomes in neonatal seizures. Improved antenatal and neonatal clinical practices may help reduce adverse outcomes in these patients.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Ameliorating effect of N-acetylcysteine and curcumin on pesticide-induced oxidative DNA damage in human peripheral blood mononuclear cells.

Endosulfan, malathion, and phosphamidon are widely used pesticides. Subchronic exposure to these contaminants commonly affects the central nervous system, immune, gastrointestinal, renal, and reproductive system. There effects have been attributed to increased oxidative stress. This study was conducted to examine the role of oxidative stress in genotoxicity following pesticide exposure using peripheral blood mononuclear cells (PBMC) in vitro. Further possible attenuation of genotoxicity was studied using N-acetylcysteine (NAC) and curcumin as known modulators of oxidative stress. Cultured mononuclear cells was isolated from peripheral blood of healthy volunteers, and exposed to varying concentrations of different pesticides: endosulfan, malathion, and phosphamidon for 6, 12, and 24 h. Lipid peroxidation was assessed by cellular malondialdehyde (MDA) level and DNA damage was quantified by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) using ELISA. Both MDA and 8-OH-dG were significantly increased in a dose-dependent manner following treatment with these pesticides. There was a significant decrease in MDA and 8-OH-dG levels in PBMC when co-treated with NAC or/and curcumin as compared to pesticide alone. These results indicate that pesticide-induced oxidative stress is probably responsible for the DNA damage, and NAC or curcumin attenuate this effect by counteracting the oxidative stress.

Adipose tissue expression of UCP1 and PRDM16 genes and their association with postprandial triglyceride metabolism and glucose intolerance.

AIMS: UCP1 and PRDM16 genes, primarily involved in browning of adipose tissue that can affect lipid metabolism are also associated with diabetes risk. Therefore, we planned to study the adipose tissue expression of UCP1 and PRDM 16 genes in subjects with glucose intolerance to find out its association with postprandial triglyceride (PPTg) measures and T2DM. METHODS: A total of 30 subjects were recruited in three groups i.e., NGT, prediabetes and T2DM (NDDM + known T2DM) who were matched for age, sex and BMI. An 8-hour standardized fat challenge test was performed to study lipemic responses. UCP1 and PRDM16 genes quantification in adipose tissue was performed by real-time PCR followed by SDS PAGE. RESULTS: UCP1 gene expression in SAT was significantly lower in T2DM and prediabetes as compared to NGT group while PRDM16 gene expression was significantly lower in T2DM group as compared to NGT group. UCP1 gene expression correlated with PPTg measures as well as with glycaemic measures while PRDM16 gene expression correlated with glycaemic measures only. CONCLUSION: This study found downregulation of PRDM16 and UCP1 gene expression in SAT in subjects with glucose intolerance. The association of UCP1 gene expression with PPTg dysmetabolism may contribute to greater predisposition to T2DM.

Effect of postprandial triglycerides on DDT/ppDDE levels in subjects with varying degree of glucose intolerance.

BACKGROUND: Organochlorine pesticides such as DDT as well as postprandial hypertriglyceridemia have been linked with insulin resistance and diabetes mellitus. The cardiometabolic risk of PPhTg could also be due to its potential to increase the serum levels of this highly lipophilic pesticide. We studied the effect of postprandial triglyceride responses to a standard oral fat challenge on the levels of DDT and its metabolites in subjects with varying degree of glucose intolerance METHODS: A standard fat challenge was performed in 60 subjects who were categorized as NGT, prediabetes, and NDDM based on an earlier OGTT. Fasting and postprandial levels of serum triglycerides, plasma DDT and its metabolites were estimated and compared in the 3 groups and their association with each other, and measures of glycemia and insulin resistance were also determined. RESULTS: Peak Tg and TgAUC levels were significantly higher in NDDM group as compared to NGT and PD groups. TgAUC showed positive correlation with fasting plasma glucose (r=0.33, p=0.01), postprandial plasma glucose (r=0.39, p=0.002) and HOMA IR(r=0.63, p=0.001). ppDDE levels were found to be significantly higher in NDDM subjects compared with NGT group. ppDDE-AUC was significantly higher in the NDDM group compared with the other two study groups. Mean ppDDE levels also showed strong positive correlation with peak Tg (r=0.295 p=0.022), TgAUC (r=0.303 p=0.018), iPPTgAUC(r=0.57 p≤0.001) and iPPpeakTg(r=0.51 p≤0.001) as well as with FPG (r=0.269 p=0.038) PPPG (r=0.424 p=0.001) and HbA1c (r=0.321 p=0.012). CONCLUSION: The findings of this study support the concept that the cardiometabolic risk associated with PPhTg may at least in part be related to the associated increase in serum levels of lipophilic OCPs like DDT.

Relationship of possible stress-related biochemical markers to oxidative/antioxidative status in obsessive-compulsive disorder.

Free radicals have been found to play an important role in obsessive-compulsive disorder (OCD). So, we measured the oxidative/antioxidative status of OCD patients, and assessed its use as a biological marker. The study was carried out on 20 healthy and 20 OCD subjects, aged between 20 and 40 years. Biochemical parameters of all subjects were assessed and compared. A significant difference in superoxide dismutase (SOD) levels was observed between the OCD and control groups (p < 0.05); malondialdehyde (MDA) levels were also significantly higher in OCD subjects (p < 0.05). Our study found an overall oxidative imbalance in OCD, leaning towards the antioxidant side in sufferers (specifically towards SOD). SOD has a protective role in overcoming oxidative stress; therefore, oxidative stress could have a pathophysiological role in OCD. Therapy specifically targeting MDA production will have a beneficial effect in overcoming the oxidative stress, anxiety and affective disorder which may be associated with OCD.

Maternal and cord blood levels of aldrin and dieldrin in Delhi population.

Aldrin and dieldrin, structurally similar organochlorine pesticides belong to cyclodiene family and were widely used for agriculture and public health program in India. Although the manufacturing, use and import of aldrin and dieldrin have been banned in India since 2003, these pesticides are still persistent in environment and may be associated with adverse neurological and reproductive effects. The aim of this study is to assess the recent exposure level of aldrin and dieldrin and their placental transfer to fetus in normal healthy full-term pregnant women belonging to north Indian population undergoing normal delivery at Obstetrics and Gynecology department of UCMS and GTB hospital, Delhi. Quantitative analysis of aldrin and dieldrin residues in maternal and cord blood samples were carried out by gas chromatography system equipped with electron capture detector. The results of our study clearly revealed that maternal and cord blood levels of aldrin and dieldrin of pregnant women are age and dietary habit dependent. The aldrin level in maternal blood and dieldrin level in cord blood are higher in women in the age group 25-30 years than in women in age group of 19-24 years. Similarly, aldrin level in maternal blood is significantly higher in women with non-vegetarian dietary habit than in women with vegetarian dietary habit. No significant association is found for maternal and cord blood level. The results of the present study clearly demonstrate prenatal uptake of aldrin and dieldrin and provide recent information on the subsequent transplacental transfer.

Induction of oxidative stress and histopathological changes by sub-chronic doses of triazophos.

The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with aconcomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histoarchitectural alterations at sub-chronic doses of triazophos in rats.

Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: attenuation by Withania somnifera.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immunomodulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus.

PURPOSE: Peroxisome proliferator-activated receptor γ (PPARγ) gene is strongly associated with type 2 diabetes mellitus, as well as postprandial lipemia, and plays an important role in Wnt dependent adipogenesis in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We aimed to study the expression of PPARγ gene in SAT and VAT to find out its correlation with postprandial hypertriglyceredemia and glucose intolerance. METHODS: Thirty subjects who were scheduled to undergo abdominal surgery were recruited in three groups (n = 10 in NGT, n = 10 in prediabetes, and n = 10 in T2DM). A standardized oral fat challenge was performed. Anthropometry, plasma glucose, HbA1c, and fasting serum insulin were also measured. SAT and VATs were collected during surgery for PPARγ gene expression studies by real-time PCR. RESULTS: PPARγ gene expression was 5.5-fold lower in T2DM and 1.7-fold lower in prediabetes as compared with NGT subjects in VAT. There was a significant negative correlation of expression of PPARγ gene in VAT {Tgauc (r = -0.57, p < 0.007), Peak Tg (r = -0.51, p < 0.01)} as well as in subcutaneous adipose tissue {Tgauc (r = -0.45, p < 0.02)} with PPTg responses measures. CONCLUSION: Reduced adipocyte expression of PPARγ gene and the resultant postprandial hypertriglyceredemia is associated with greater risk of diabetes and prediabetes.