B.D. Banerjee

Modulation of stress-induced neurobehavioral changes by nitric oxide in rats

The involvement of nitric oxide (NO) in stress-induced neurobehavioral changes in rats was evaluated using the elevated plus maze and open field tests. Restraint stress (1 h) reduced both the number of entries and time spent in open arms, with both expressed as percent of controls (no restraint stress), and these changes were reversed with diazepam (1 mg/kg) and the NO precursor, L-arginine (500 and 1000 mg/kg) pretreatment. The nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg), aggravated restraint stress effects in the elevated plus maze test, whereas the lower dose (10 mg/kg) of the drug attenuated the same. In the open field test, the restraint stress-induced (a) increased entry latency and (b) decreased ambulation and rearing were reversed by diazepam and L-arginine and L-NAME (10 mg/kg), whereas L-NAME (50 mg/kg) aggravated restraint stress effects. The neuronal nitric oxide synthase inhibitor, 7-nitroindazole (10 and 50 mg/kg), did not influence these restraint stress-induced behavioral changes to any significant extent. Biochemical data showed that L-NAME (10 and 50 mg/kg.) induced opposite effects on the total brain nitrate/nitrite content during restraint stress. The results indicate a possible involvement of NO in stress-induced neurobehavioral effects.

Organochlorine pesticide residue levels and oxidative stress in preterm delivery cases

A number of studies have focused attention on various biochemical abnormalities evoked due to exposure to organochlorine pesticides (OCPs). The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and assess the levels of different non-enzymatic oxidative stress markers as well as to establish correlation with OCP levels, if any. Thirty women in each group of full-term delivery (FTD; ≥37 weeks of gestation) and preterm delivery (PTD; <37 weeks of gestation) were enrolled in this study. Levels of OCPs like Hexachlorocyclohexane (HCH), endosulfan, p,p′ Dichlorodiphenyldichloroethylene (DDE) and p,p’ Dichlorodiphenyltrichloroethane (DDT) were analyzed by gas chromatography. Non-enzymatic oxidative stress was measured by the quantification of malondialhyde (MDA), protein carbonyl, reduced glutathione (GSH) and ferric-reducing ability of plasma (FRAP). MDA and protein carbonyl levels were increased significantly, while the levels of GSH and FRAP were decreased in PTD in comparison to FTD cases. We have observed higher levels of β-HCH and α-endosulfan and increased oxidative stress in PTD than FTD cases. In PTD cases, a significant positive correlation was observed between maternal blood levels of β-HCH and MDA (r = .78), β-HCH and GSH (r = —.65), γ-HCH and MDA (r = .89), γ-HCH and GSH (r = —.74) and α-endosulfan and MDA (r = .54) in PTD cases. We also found significant correlations between cord blood levels of β-HCH and MDA (r = .59), β-HCH and GSH (r = —.69), γ-HCH and MDA (r = .62) and α-endosulfan and MDA (r = .54) in PTD cases. In conclusion, our results suggest that higher levels of some of the OCP residues may be associated with PTD and increased oxidative stress.

Organochlorine pesticide levels and risk of Alzheimer’s disease in north Indian population

Alzheimer’s disease (AD) could result from a multifactorial process involving both genetic predisposition and exposure to environmental factors like pesticides. A case control study of 70 patients of AD and 75 controls was done to examine the association between organochlorine pesticides (OCPs) and risk of AD. OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp′-dichlorodiphenyldichloroethylene (pp′-DDE), op′-DDE, pp′-dichlorodiphenyltrichloroethane (pp′-DDT), op′-DDT, pp′-dichlorodiphenyldichloroethane (pp′-DDD) and op′-DDD) were extracted from blood and quantitatively estimated using gas chromatography. A Mann–Whitney U test revealed significant difference in β-HCH levels (U = 1237.00, W = 4087.00, z = −6.296, p = 0.000, r = −0.71), dieldrin levels (U = 1449.00, W = 4299.00, z = −5.809, p = 0.000, r = −0.68) and pp′-DDE levels (U = 2062.00, W = 4912.00, z = −2.698, p = 0.007, r = −0.59) between AD patients and controls. In conclusion, this study supports epidemiological studies that associate exposure to pesticides with increased risk of AD, and we identified the specific pesticides β-HCH, dieldrin and pp′-DDE that are associated with the risk of AD in the north Indian population. However, further research is needed to establish the potential role of these OCPs as an etiologic agent for AD case.

Association of glutathione S-transferase M1 and T1 gene polymorphisms and oxidative stress markers in preterm labor

OBJECTIVE Oxidative stress and related gene polymorphism may be associated with the etiology of preterm labor (PTL). The present study was designed to investigate association of GSTM1 and GSTT1 gene polymorphisms with PTL and their relationship with oxidative stress markers. DESIGN AND METHODS Sixty cases of PTL and sixty three subjects of full term labor (FTL) were included in the study. Multiplex PCR was performed for GSTM1 and GSTT1 genes polymorphism and oxidative stress markers were analyzed. RESULT MDA and 8-OHdG levels were increased, while GSH was decreased in PTL than FTL subjects. Frequency of GSTM1-/GSTT1-(null) was significantly higher in PTL in comparison to FTL (p=0.028, OR=3.4). Subjects with GSTM1-/GSTT1+, GSTM1+/GSTT1-, GSTM1-/GSTT1- have significant differences of oxidative stress markers as compared to GSTM1+/GSTT1+ genotype. CONCLUSION GSTM1-/GSTT1- (null) genotype may be one of the associated genetic factor for the increased risk of PTL.

Intra uterine growth retardation: Association with organochlorine pesticide residue levels and oxidative stress markers

Intra uterine growth retardation (IUGR) is a major complication of pregnancy, affecting ∼5% to 10% of newborns. Hexachlorocyclohexane (HCH) is an organochlorine pesticide that consists of eight stereoisomers and γ-isomer is the only isomer that possesses insecticidal activity. The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and to assess the level of oxidative stress markers as well as to establish correlation with OCP levels. Fifty women delivering neonates with low birth weight (IUGR) and equal number of women delivering normal birth weight babies (control) were recruited. We have observed higher levels of γ-HCH and T-HCH and increased oxidative stress markers in IUGR subjects versus control subjects. Significant correlations were also found between HCH isomers and oxidative stress markers in IUGR subjects. In conclusion, our results suggest that higher levels of HCH isomers may be associated with IUGR and increased oxidative stress.

Association between recurrent miscarriages and organochlorine pesticide levels.

OBJECTIVES Recurrent miscarriage (RM) is a challenging medical problem because of its unknown pathogenesis and etiology in most of the cases. Recent studies suggest the role of persistent environmental pollutants such as organochlorine pesticides (OCPs) in the etiology of RM. The present study was conducted to investigate possible associations of OCPs in the pathogenesis of RM. DESIGN AND METHODS Blood OCP levels were analyzed in women with RM (cases) and women with normal full term delivery with live birth (controls) by using a gas chromatograph equipped with an electron capture detector. RESULTS A statistically significant association (p=0.01) was observed between blood gamma-HCH levels and women with recurrent miscarriages. CONCLUSIONS This study suggests that high blood levels of gamma-HCH may be associated with risk of RM.

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), β-hexachlorocyclohexane (β-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 β-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.

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

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.

Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats.

Dementia is a syndrome of progressive nature, affects wide range of cognitive abilities like memory, language, calculation and so on, neuropsychiatric and social deficits to impair the routine social functions. The present study was designed to assess the effect of curcumin against colchicine-induced cognitive dysfunction and oxidative stress in rats and compare it with rivastigmine. Colchicine (15 µg/5µl) was administered to male Wistar rats intracerebroventricularly (i.c.v.) by stereotaxic apparatus to induce cognitive dysfunction. Administration of colchicine caused poor retention of memory in elevated plus maze, passive avoidance apparatus and Morris water maze paradigms. Chronic treatment with curcumin (100, 200 and 400 mg/kg, p.o.) twice daily and rivastigmine (2.5 mg/kg, p.o.) daily for a period of 28 days beginning 7 days prior to colchicine injection significantly improved colchicine-induced cognitive impairment. Biochemical assessment revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, depleted reduced glutathione levels and decreased acetyl cholinesterase (AChE) activity in rat brains. Chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the reduced glutathione levels and AChE activity; however, rivastigmine failed to prevent oxidative stress. The results of the current study indicate that curcumin (100, 200 and 400 mg/kg, p.o.) twice daily has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.

Pharmacological and biochemical studies on the role of free radicals during stress-induced immunomodulation in rats

The present study was designed to evaluate the role of free radicals in restraint stress (RS)-induced modulation of immune responses in rats. RS significantly suppressed both humoral and cell-mediated immune responses as evidenced by reduced (a) anti-SRBC antibody titre (b) splenic Plaque Forming Cell counts, (c) footpad thickness response, and (d) IFN-γ and IL-4 levels. Assay for oxidative stress markers in blood showed that there was significant enhancement in plasma corticosterone and products of lipid peroxidation, viz. malondialdehyde and lowered reduced glutathione levels on exposure to RS. Further, this was associated with decreased antioxidant enzyme activity, viz. superoxide dismutase and catalase. These RS-induced changes in immunological and oxidative stress markers were markedly attenuated by pretreatment with the antioxidants, L-ascorbic acid (100 and 200 mg/kg) and α-tocopherol (30 and 60 mg/kg), by differential degrees. The combination of L-ascorbic acid and α-tocopherol was shown to have synergistic effects on reversal of these RS-induced effects. The results suggest that reactive oxygen species may be involved in stress-induced immunomodulation.