Involvement of oxidative stress-related apoptosis in chlorpyrifos-induced cytotoxicity and the ameliorating potential of the antioxidant vitamin E in human glioblastoma cells.

Organophosphate pesticides (OPs), which are among the most widely used synthetic chemicals for the control of a wide variety of pests, are however associated with various adverse reactions in animals and humans. Chlorpyrifos, an OP, has been shown to cause various health complications due to ingestion, inhalation, or skin absorption. The mechanisms underlying the adverse effect of chlorpyrifos on neurotoxicity have not been elucidated. Therefore, we aimed to determine the mechanism of chlorpyrifos-induced cytotoxicity and to examine whether the antioxidant vitamin E (VE) ameliorated these cytotoxic effects using DBTRG-05MG, a human glioblastoma cell line. The DBTRG-05MG cells were treated with chlorpyrifos, VE, or chlorpyrifos plus VE and compared with the untreated control cells. Chlorpyrifos induced a significant decrease in cell viability and caused morphological changes in treated cultures. Furthermore, chlorpyrifos led to the increased production of reactive oxygen species (ROS) accompanied by a decrease in the level of reduced glutathione. Additionally, chlorpyrifos induced apoptosis by upregulating the protein levels of Bax and cleaved caspase-9/caspase-3 and by downregulating the protein levels of Bcl-2. Moreover, chlorpyrifos modulated the antioxidant response by increasing the protein levels of Nrf2, HO-1, and NQO1. However, VE reversed the cytotoxicity and oxidative stress induced by chlorpyrifos treatment in DBTRG-05MG cells. Overall, these findings suggest that chlorpyrifos causes cytotoxicity through oxidative stress, a process that may play an important role in the development of chlorpyrifos-associated glioblastoma.

A Novel Electrochemical Biosensor Based on Polyaniline-Embedded Copper Oxide Nanoparticles for High-Sensitive Paraoxon-Ethyl (PE) Detection.

This paper proposes a fabrication of a hyper-sensitive amperometric biosensor for paraoxon-ethyl (PE) detection. In this developed biosensor, polyaniline (PANI) and copper oxide (CuO)-based nanocomposite is used as a sensing platform. The homogeneous distribution of CuO onto the PANI matrix enhances the surface area and conductivity of the nanocomposite. Additionally, the PANI produces a compatible environment for enzyme immobilization, which further enhances the rate of electron transfer. For biosensor fabrication, the nanocomposite is deposited electrophoretically onto the ITO glass substrate and immobilization of acetylcholinesterase (AChE) enzyme is conducted onto the fabricated electrode surface. The results validate good reproducibility, good stability, and high selectivity of the fabricated biosensor (AChE/PANI@CuO/ITO). The inhibition rate of paraoxon-ethyl (PE) is recorded in the concentration range of 1-200 nM with a low limit of detection of 0.096 nM or 96 pM. The sensitivity of the developed biosensor is found to be 49.86 µA(nM)-1. The developed biosensor is further successfully accomplished for the detection of PE in real samples like rice and pulse.

Associations of organophosphate metabolites with thyroid hormone and antibody levels: findings from U.S. National Health and Nutrition Examination Survey (NHANES).

Studies have shown that organophosphate pesticides (OPs) exposure may disrupt thyroid endocrine functions in animal models, agricultural population, occupational workers, and work-related population. However, the relationships between OPs exposure and thyroid hormone levels in the general population are unclear. This study aimed to explore the relationships of OPs exposure with thyroid hormone and antibody levels in the general population. We analyzed a sample of 1089 US adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2002. OPs exposure was estimated using measures of six non-specific dialkyl phosphate metabolites (DAPs), e.g., dimethylphosphate (DMP). Multiple linear regression models were used to examine the associations of OPs exposure with thyroid hormone and antibody levels. The medians of urinary ∑DAPs detected in males and females were 32.98 nmol/g creatinine and 40.77 nmol/g creatinine, with statistical significance (p = 0.001). After controlling for sociodemographic factors, we found that concentrations of urinary OPs metabolites were positively associated with the serum thyroid stimulating hormone (TSH) in the general US population, particularly in males; OPs metabolites were associated with the serum TgAb, tT3, fT3, and TSH. These findings showed that thyroid hormone and antibody disruption are probably associated with OPs exposure in the general population; more studies are needed to confirm our findings.

Prediction of dose-dependent in vivo acetylcholinesterase inhibition by profenofos in rats and humans using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry.

Organophosphate pesticides (OPs) are known to inhibit acetylcholine esterase (AChE), a critical effect used to establish health-based guidance values. This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. A physiologically based kinetic (PBK) model was developed for both species. Parameter values for profenofos conversion to 4-bromo-2-chlorophenol (BCP) were derived from in vitro incubations with liver microsomes, liver cytosol, and plasma from rats (catalytic efficiencies of 1.1, 2.8, and 0.19 ml/min/mg protein, respectively) and humans (catalytic efficiencies of 0.17, 0.79, and 0.063 ml/min/mg protein, respectively), whereas other chemical-related parameter values were derived using in silico calculations. The rat PBK model was evaluated against literature data on urinary excretion of conjugated BCP. Concentration-dependent inhibition of rat and human AChE was determined in vitro and these data were translated with the PBK models to predicted dose-dependent AChE inhibition in rats and humans in vivo. Comparing predicted dose-dependent AChE inhibition in rats to literature data on profenofos-induced AChE inhibition revealed an accurate prediction of in vivo effect levels. Comparison of rat predictions (BMDL10 of predicted dose-response data of 0.45 mg/kg bw) and human predictions (BMDL10 of predicted dose-response data of 0.01 mg/kg bw) suggests that humans are more sensitive than rats, being mainly due to differences in kinetics. Altogether, the results demonstrate that in vivo AChE inhibition upon acute exposure to profenofos was closely predicted in rats, indicating the potential of this novel approach method in chemical hazard assessment.

Organophosphate pesticide exposure in school-aged children living in rice and aquacultural farming regions of Thailand.

Organophosphate pesticides (OPs) are widely used in agricultural sectors in Thailand. Previous studies have documented that children residing in agricultural areas have higher exposure to OPs than children living in other residential areas. The objective of this study was to quantify urinary biomarkers of OP exposure and determine the environmental conditions and activities that predict their levels among children living in Central Thailand farming regions. In October 2011, 53 6-8-year-old participants were recruited from Pathum Thani Province, Thailand. Twenty-four lived in rice farming communities at Khlong Luang District where OPs are the pesticides used frequently. Twenty-nine participants, living in aquacultural farming communities at Lum Luk Ka District where OPs are not used, were recruited to serve as controls for pathways of exposure (e.g., residential, dietary) other than occupational/paraoccupational exposures encountered in rice farming. Household environments and participants' activities were assessed using a parental structured interview. Urine samples (first morning voids) were collected from participants for OP urinary metabolite (i.e., dialkylphosphates [DAPs] and 3,5,6-trichloro-2-pyridinol [TCPy]) measurements. The levels of most urinary OP metabolites were significantly higher in participants who lived in a rice farming community than those who lived in an aquacultural farming community (P < .05). The results from linear regression analysis revealed that the frequency of OP application on rice farms (∑DAP: P = .001; TCPy: P = .001) and living in a rice farming community (∑DAP: P = .009; TCPy: P < .001) were significant predictors of urinary DAP metabolite levels in participants. Increasing TCPy levels were significantly related to proximity to rice farm (P = .03), being with parent while working on a farm (P = .02), playing on a farm (P = .03), and the presence of observable dirt accumulated on the child's body (P = .02). In conclusion, OP metabolite levels among children who live in rice farming communities were strongly influenced by farming activity, household environments, and child behaviors, suggesting that these are the primary pathways in which children living in these agricultural communities in Thailand were exposed to OPs.