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The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

In this study, nerve conduction, organochlorine (OC) pesticide residues in blood and cholinesterase activity levels of pesticide sprayers employed in mango plantations at Lucknow, North India, were determined. Fifty-two sprayers from mango plantations who regularly spray mixture of pesticides like organophosphates (OP), OCs, and carbamates were considered as exposed group. Eighteen subjects with similar socio-economic status of exposed group, who do not handle pesticides, were selected as controls. Questionnaire-based interviews related to personal and occupational histories of the study subjects were carried out. Sprayers did not use any personal protective equipment during pesticide handling. The blood-pesticide analyses of sprayers show higher mean values of hexachlorohexane (HCH), γ-HCH, δ-HCH, total HCH, op-DDT compared with the controls. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activites were significantly reduced among sprayers. Risk of motor nerve conduction deficits was observed in sprayers with low AChE activity. Negative correlation of motor and sensory nerve conduction deficits was observed with the duration of exposure and age among sprayers. The study demonstrated that the prolonged exposure to mixture of pesticides, ergonomic factors, decline in cholinesterase activity may lead to nerve conduction dysfunction. The findings suggest the need for controlled use of pesticides in the plantation and indicated the need for training and implementation of hygiene practices like proper usage of personal protective equipments. [ABSTRACT FROM AUTHOR]

Long-term exposure to cypermethrin induces the nigrostriatal dopaminergic neurodegeneration in adult rats and its pre-exposure in the critical periods of brain development enhances the susceptibility during adulthood. Monoamine transporters, xenobiotic metabolizing enzymes and oxidative stress play critical roles in the nigrostriatal dopaminergic neurodegeneration. The study was undertaken to investigate the effects of cypermethrin on DAT, VMAT 2, CYP2E1, GST Ya, GST Yc and GSTA4-4 expressions, CYP2E1 and GST activities and lipid peroxidation in the nigrostriatal system of adult rats with/without post-natal exposure to cypermethrin. Cypermethrin reduced VMAT 2 and increased CYP2E1 expressions without causing significant change in DAT. Although GSTA4-4 mRNA expression and lipid peroxidation were increased, no significant changes were observed in GST Ya and GST Yc expressions and total GST activity. The results obtained demonstrate that long-term exposure to cypermethrin modulates VMAT 2, CYP2E1, GSTA4-4 expressions and lipid peroxidation, which could contribute to the nigrostriatal dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the hematological and cholinesterase (ChE) activity levels of pesticide sprayers employed in mango plantations at Lucknow. Fifty-two sprayers from mango plantations who regularly spray mixtures of pesticides including organochlorines (OC), organophosphates (OP), and carbamates were included as exposed group. Twenty residents living close to mango plantations, but not involved in pesticide spraying were taken as controls. Pesticide residues for OC were analyzed in blood by gas chromatography with electron capture detector. There was a significant decrease in acetylcholinesterase and butyrylcholinesterase activities in pesticide sprayers (n = 52) relative to the control group (n = 20). A significant difference in the frequency distribution of hematological variations in red blood cell, white blood cell, monocytes, neutrophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count was observed. Residues of OC pesticides including α-hexachlorocyclohexane (HCH) and total HCH were found to be significantly higher in the blood of sprayers compared to controls. Hematological variations were quantitatively more frequent among the sprayers with 5 years of pesticide exposure compared to the controls and to subjects with less than 5 years of exposure group. Hematological abnormalities in sprayers were correlated with pesticide exposure as evidenced by lower ChE activity as well as the presence of OC pesticides in blood. The poorly controlled use of pesticides in the plantation appeared to have produced sub-clinical intoxication in the sprayers and indicated the need for training and implementation of proper, safer hygiene practices. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in Parkinson's disease (PD). Metallothioneins (MT), cytochrome P450 IIE1 (CYP2E1) and glutathione S-transferases alpha4-4 (GSTA4-4) are involved in oxidative stress-mediated damage. Altered dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are also documented in PD. The present study was undertaken to investigate the effect of Zn and PQ co-exposure on neurodegeneration in rats. A significant reduction was observed in spontaneous locomotor activity (SLA), striatal dopamine (DA) levels, tyrosine hydroxylase (TH) immunoreactivity, glutathione reductase (GR) and catalase activity along with increased lipid peroxidation (LPO) and glutathione peroxidase (GPx) activity after Zn and/or PQ exposure. Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II, but reduced the expression of VMAT-2. Protein expression analysis of TH, VMAT-2 and DAT showed results similar to those obtained with gene expression study. Zn and PQ co-exposure caused a more pronounced effect than that of individual exposure. The results obtained in this study suggest that, similar to PQ, Zn induced neurodegeneration via alterations in oxidative stress and expression of the above-mentioned genes. However, the effect of Zn+PQ was only slightly higher than that of alone, indicating that probably Zn and PQ follow some different molecular events leading to neurodegeneration. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS), a progressive disorder that usually runs a fatal course within 2-5 years of onset, is characterized by loss of motor neurons in the cortex, brain stem, and spinal cord. In this study mercury (Hg) concentrations were determined in blood samples of 40 ALS patients, of whom 24 ALS patients were from the Ganga plain region and their metal levels were found to be significantly higher. In contrast, Hg levels in the 16 ALS patients from non-Ganga plain regions whose levels were similar to those of the control subjects. Mercury in stream water samples and freshly deposited stream sediment were determined in the locations of patients' native residences along the Ganga plain region and metal levels were found to be higher than the threshold guideline values for Hg in stream waters recommended by WHO. The geo-accumulation index in selected sites of freshly deposited stream sediment ranged from moderate to highly polluted. The high levels of Hg observed in ALS patients may potentially alter the redox status of neuronal cell components and induce cell-death pathways. [ABSTRACT FROM AUTHOR]

Hemoglobin mediated cytotoxicity and apoptosis has been evaluated in Tumor necrosis factor-α(TNF-α) sensitive cell line, U937 and compared with TNF-α. Both species of hemoglobin, Hemoglobin A2 and Hemoglobin A0 induced apoptosis and cytotoxicity in U937 cell as measured by flow cytometry and 3-(4,5-dihydro-6-(4-(3,4-dimethoxybenzooyl)-1-piperazinyl)-2(1H)-quinoline(MTT) assay respectively. Different concentration of Hemoglobin A0(4 ng/mL to 4000 ng/mL) induced apoptosis ranging from 9% to 16% in U937 cells. 4000 ng/mL hemoglobin A0 showed maximal apoptotic cells. TNF-α showed 87% apoptotic U937 cells at concentration of 1 pg/mL. HbA0 displayed cytotoxicity in U937 cell line at higher concentration in comparison to TNF-α. 4000 ng/mL of hemoglobin A0 showed optimal cytotoxic response in U937 cells. A dose response curve was also observed with varying doses of hemoglobin A0. U937 cells pretreated with serum activated LPS for 1 hr and incubated with different concentration of hemoglobin or human TNF-α for 24 h reduced the cytotoxic effect on U937. Dexamethasone treatment of U937 cells helped in protecting the HbA0 and HbA2 mediated cytotoxicity and anti-TNF-α antibody neutralized the hemoglobin mediated apoptosis and cytotoxicity. It is therefore apparent that human hemoglobin shares some of the bioactivities previously ascribed to TNF-α. Sharing of bioactivities of TNF-α by hemoglobin is interesting and suggests that cell free hemoglobin can mimic TNF-α functionally. [ABSTRACT FROM AUTHOR]