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Parkinson's disease (PD) is one of the most common neurodegenerative disorders with limited clinical interventions. A number of epidemiological as well as case-control studies have revealed an association between pesticide exposure, especially of paraquat (PQ) and occurrence of PD. Hsp70, a molecular chaperone by function, has been shown as one of the modulators of neurological disorders. However, paucity of information regarding the protective role of Hsp70 on PQ-induced PD like symptoms led us to hypothesize that modulation of hsp70 expression in the dopaminergic neurons would improve the health of these cells. We took advantage of Drosophila, which is a well-established model for neurological research and also possesses genetic tools for easy manipulation of gene expression with limited ethical concern. Over-expression of hsp70 was found to reduce PQ-induced oxidative stress along with JNK and caspase-3 mediated dopaminergic neuronal cell death in exposed organism. Further, anti-apoptotic effect of hsp70 was shown to confer better homeostasis in the dopaminergic neurons of PQ-exposed organism as evidenced by their improved locomotor performance and survival. The study has merit in the context of human concern since we observed protection of dopaminergic neurons in PQ-exposed organism by over-expressing a human homologue of hsp70, HSPA1L, in these cells. The effect was parallel to that observed with Drosophila hsp70. These findings reflect the potential therapeutic applicability of hsp70 against PQ-induced PD like symptoms in an organism. [ABSTRACT FROM AUTHOR]

A dimensionless numerical investigation of turbulent flow and heat transfer characteristics due to the impingement of a free inclined slot jet onto the moving hot surface has been performed using the k − ω turbulence model. The parameters considered for the investigation are: the Reynolds number, impingement angle and plate velocity. The influence of parameters on the properties such as the pressure and velocity profiles, skin-friction coefficients, Nusselt number, interface temperature, and the location of stagnation has been presented. The displacement of stagnation point depends primarily on ϕ , whereas the effect of plate velocity is less significant. These relocations are found in between X = − 2 to 0. The effect of plate velocity on average skin-friction coefficient is continuously decreasing with increase in jet angle. A continuous increase in average Nu has been found with increase in Re for all values of ϕ and U p considered in the present study. It is revealed that the change in plate velocity has more influence on the average Nu for lower angles of impingement. Further reduction in the impingement angle shows an adverse effect on the average Nu. Correlations have been developed for Nusselt number at different zones based on the parameters considered for the study. [ABSTRACT FROM AUTHOR]

Fipronil is a highly effective, broad-spectrum insecticide used to control pests, globally. The increased usage has led to contamination of soil, water, fruits, and vegetables. The wide and frequent usage of fipronil across the globe calls for attention regarding risk assessment of undesirable effects on non-target microorganisms. In this context, the present study was carried to understand the impact of fipronil on non-pathogenic Escherichia coli. The non-pathogenic E. coli are important commensal of the intestinal tract of humans and animals and are also indicator organisms in the environment. Our study indicates that exposure of E. coli to fipronil (100 μM concentration) leads to significant reactive oxygen species production, loss of membrane potential and viability. Further, we have witnessed the bioaccumulation and biotransformation of fipronil by E. coli at non-lethal concentrations. The bio-transformed products (fipronil sulfone and fipronil sulfide) are also the major metabolites (along with amide) reported in the feces of the mammals when exposed to fipronil. Thus, there is a possibility that the gut E. coli might play a role in the degradation and thereby removal of fipronil. In addition, the bioaccumulation of fipronil in bacteria is of concern and need to be further explored because it can lead to biomagnification in the higher trophic level and can disturb the ecological balance. In our knowledge, this is the first report on the determination of fipronil and its metabolites in bacteria through GC-MS/MS. Image 1067 • Fipronil at 100 μM concentration is toxic to E. coli. • E. coli K12 biotransforms fipronil into fipronil sulfone and fipronil sulfide. • Fipronil bioaccumulates in bacteria. [ABSTRACT FROM AUTHOR]

Abstract: Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A549. The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite. [Copyright &y& Elsevier]

β-triketone herbicides have been efficiently employed as an alternate to atrazine. Triketones are 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme inhibitors and exposure is reported to cause significant increase in plasma tyrosine levels. In this study, we have employed a non-target organism Caenorhabditis elegans to determine the impact of β-triketone exposures at recommended field doses (RfD). Our results indicate sulcotrione and mesotrione, negatively influence the survival, behavior, and reproduction of the organism at RfD. Additionally, we have traced the parallels regarding the impact of triketones on the tyrosine metabolism pathway, in C. elegans to those in mammalian models, wherein the expression of the tyrosine metabolism pathway genes are altered, directly influencing tyrosine catabolism leading to significant tyrosine accumulation in exposed organism. Further, we investigated the impact of sulcotrione and mesotrione exposure on fat deposition (triglyceride levels, Oil-Red-O staining and lipidomics) and the fatty acid metabolism pathway. In the exposed worms, the expression of enlongases and fatty acid desaturases were up-regulated along with an increase in the levels of triglycerides. Thus, the data indicates a positive association of β-triketone exposure to mis-regulation of the fatty acid metabolism pathway genes leading to fat accumulation in worms. Therefore, β-triketone might be a potential obesogen. [Display omitted] • β-triketone significantly impacts behavior, and reproduction in C. elegans. • β-triketone exposure causes tyrosine and triglyceride accumulation in C. elegans. • Up-regulation of desaturases and elongases leads to fat deposition in exposed worms. [ABSTRACT FROM AUTHOR]

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction. [Display omitted] • Bisphenol A (BPA) induces type 2 diabetes (T2D) like condition in Drosophila. • BPA induced oxidative stress results in fibrosis of Malpighian tubules (MTs). • Fibrosis in the MTs results in the structural deformities in them. • Structural deformities result in reduced function of MTs and shortened life span of Drosophila. • BPA + high sucrose diet (HSD) further increased the magnitude of T2D and MTs dysfunction parameters. [ABSTRACT FROM AUTHOR]

Abstract: In this in vitro study we investigated the toxic responses in hepatocytes treated with occupational dust to which workers are exposed in bone-based industrial units. The present study investigated the toxicity mechanism of bone-based occupational dust, from a particular industrial unit, on isolated rat hepatocytes. The hepatocytes were isolated by collagenase perfusion method and cell viability was determined by trypan blue exclusion and MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay treated with occupational dust at 0.1–1.0mgmL−1, for 120min. The cell viability decreased significantly in a concentration-dependent manner. Dust induced significant membrane damage measured by lactate dehydrogenase (LDH) and glutathione (GSH) release in culture media for 30-, 60- and 120min treatment duration. The toxicity was found to be correlated with the induction of lipid peroxidation (LPO). In addition, nitric oxide (NO), and hydrogen peroxide (H2O2) generation by occupational dusts were also found to be time- and concentration-dependent. Over all the present study provides initial evidences for the toxic potential of occupational dust generated in bone-based industries and, therefore, the dust exposure to workers in unorganized industrial units should be controlled. [Copyright &y& Elsevier]

Abstract: Experimental studies have shown that toxicant responsive genes, cytochrome P450s (CYPs) and glutathione S-transferases (GSTs) play a critical role in pesticide-induced toxicity. CYPs play pro-oxidant role and GSTs offer protection in maneb (MB) and paraquat (PQ)-induced brain and lung toxicities. The present study aimed to investigate the effect of repeated exposures of MB and/or PQ on lipid peroxidation (LPO), glutathione content (GSH) and toxicant responsive genes, i.e., CYP1A1, 1A2, 2E1, GSTA4-4, GSTA1-1 and GSTA3-3 in the liver and to correlate the same with polymorphonuclear leukocytes (PMNs). A significant augmentation in LPO and reduction in GSH content was observed in a time of exposure dependent manner in the liver and PMNs of MB and/or PQ treated animals. The expression and catalytic activity of CYP2E1 and GSTA4-4 were significantly increased following MB and/or PQ exposure both in the liver and PMNs. Although the expression of GSTA3-3 was increased, the expression of GSTA1-1 was unaltered after MB and/or PQ treatment in both the liver and PMNs. MB augmented the expression and catalytic activity of CYP1A1 in the liver, however, CYP1A2 was unaffected. PQ, on the other hand, significantly increased hepatic CYP1A2 expression and catalytic activity. MB and/or PQ did not produce any significant changes in CYP1A1 and CYP1A2 in PMNs. The results of the study thus demonstrate that MB and PQ differentially regulate hepatic CYP1A1 and CYP1A2 while LPO, GSH, CYP2E1, GSTA4-4 and GSTA3-3 are modulated in the similar fashions both in the liver and PMNs. [Copyright &y& Elsevier]

Parabens, the alkyl esters of p -hydroxybenzoic acid such as methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP) are used as a preservative in food, personal care products (PCPs), and pharmaceuticals, due to their antimicrobial properties. Parabens are continuously released into the environment, during washout of PCPs, disposal of industrial waste from the pharmaceutical and paper industries. Parabens have been detected in the indoor dust, wastewater stream, surface water of rivers, and the marine system. Recent eco-toxicological data and the environmental presence of parabens, has raised concerns regarding the safety and health of environment/humans. Thus, to further understand the toxicity of parabens, the present study was carried out in the soil nematode and well established biological model organism Caenorhabditis elegans. In the present study, LC 50 of MeP, EtP, PrP and BuP for 72 h exposures from L1 larva to adult stage was found to be 278.1, 217.8, 169.2, and 131.88 μg/ml, respectively. Further exposure to 1/5th of LC 50 of parabens yielded an internal concentration ranging from 1.67 to 2.83 μg/g dry weight of the organism. The toxicity of parabens on the survival, growth, behavior, and reproduction of the C. elegans was found in the order of BuP > PrP > EtP > MeP. Worms exposed to parabens show significant down-regulation of vitellogenin genes, high levels of reactive oxygen species and anti-oxidant transcripts, the latter being concordant with nuclear localization of DAF-16 and up-regulation of HSF-1 and SKN-1/Nrf. Hence, parabens caused endocrine disruption, oxidative stress and toxicity in C. elegans at environment relevant internal concentration of parabens. Image 10156 • The order of toxicity of parabens in C. elegans is BuP > PrP > EtP > MeP. • Parabens caused down-regulation of vitellogenins in C. elegans. • Parabens induced ROS and antioxidant response in C. elegans. • Cellular response to parabens is mediated through DAF-16, HSF-1, and SKN-1 transcription factors in C. elegans. [ABSTRACT FROM AUTHOR]