Fenitrothion induces glucose metabolism disorders in rat liver BRL cells by inhibiting AMPKα and IRS1/PI3K/AKT signaling pathway.

Fenitrothion (FNT) is a common organophosphorus pesticide that is widely used in both agricultural and domestic pest control. FNT has been frequently detected in various environmental media, including the human body, and is a notable contaminant. Epidemiological investigations have recently shown the implications of exposure to FNT in the incidence of various metabolic diseases, such as diabetes mellitus in humans, indicating that FNT may be a potential endocrine disruptor. However, the effects of FNT exposure on glucose homeostasis and their underlying mechanisms in model organisms remain largely unknown, which may limit our understanding of the health risks of FNT. In this study, FNT (4 5, 90, 180, and 4 50 µM) exposure model of rat hepatocytes (Buffalo Rat Liver, BRL cells) was established to investigate the effects and potential mechanisms of its toxicity on glucose metabolism. Several key processes of glucose metabolism were detected in this study. The results showed significantly increased glucose levels in the culture medium and decreased glycogen content in the FNT-exposed BRL cells. The results of quantitative real-time PCR and enzymology showed the abnormal expression of genes and activity/content of glucose metabolic enzymes involved in glucose metabolism, which might promote gluconeogenesis and inhibit glucose uptake, glycolysis, and glycogenesis. Furthermore, gluconeogenesis and glycolytic were carried out in the mitochondrial membrane. The abnormal of mitochondrial membrane potential may be a potential mechanism underlying FNT-induced glucose metabolism disorder. In addition, the mRNA and protein expression implicated that FNT may disrupt glucose metabolism by inhibiting the AMPKα and IRS1/PI3K/AKT signaling pathways. In conclusion, results provide in vitro evidence that FNT can cause glucose metabolism disorder, which emphasizes the potential health risks of exposure to FNT in inducing diabetes mellitus.

Pesticides in surface water of the Ondas river watershed, western Bahia, Brazil: Spatial-seasonal distribution and risk assessment.

This study investigated the occurrence and seasonal distribution of different classes of pesticides in surface waters of the Ondas River Watershed, as well as potential risks to the aquatic health and human water consumption in the western region of Bahia state, Brazil. Two gas chromatography-mass spectrometry analytical methods were applied to monitor 34 pesticides in water samples collected during both the dry and rainy seasons at 17 sites. Upon individual analysis, only γ-HCH, methoxychlor, demeton-S, methyl parathion, fenitrothion, chlorpyrifos, and azoxystrobin exhibited statistically significant differences between seasons. During rainy season, concentration medians of residues were higher for γ-HCH (74.7 ng L-1), methoxychlor (25.1 ng L-1), and azoxystrobin (47.2 ng L-1), potentially linked to historical contamination or illegal use. Conversely, pesticides like methyl parathion, fenitrothion, and chlorpyrifos, belonging to the organophosphate class, showed higher concentration medians in the dry period, measuring 75.1, 5.50, and 10.8 ng L-1, respectively, probably due to region crop activities. The risk quotient (RQ) assessment for aquatic life indicated that 59.0% of the samples in the dry season and 76.0% in the rainy season had RQ values greater than one, signifying a critical scenario for species conservation. Regarding human consumption, elevated risks were observed for heptachlor in both sampling periods and for azoxystrobin during the rainy season, surpassing RQ levels above 1, indicating danger in untreated water ingestion. Additionally, 24.0% and 53.0% of the samples in the dry and rainy seasons, respectively, contained at least one pesticide exceeding the EU resolution limit (100 ng L-1). Therefore, considering this information, implementing mitigation measures to avoid the river's contamination becomes imperative.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Ultrasensitive Fluorescence Platform Based on AgNPs In Situ-Incorporated Zr-MOFs for the Detection of Organophosphorus Pesticides.

Organophosphorus pesticides (OPPs) are extensively used in agricultural production, and the contamination caused by their residues has raised significant concerns regarding potential threats to human health. Herein, a novel fluorescence nanoprobe based on an enzyme-mediated silver nanoparticle-modified metal organic framework (AgNPs@PCN-224) was successfully prepared for the rapid detection of OPPs. Initially, AgNPs@PCN-224 were synthesized by reducing silver nitrate (AgNO3) using sodium borohydride (NaBH4) embedded into luminescent PCN-224. This triggered the inner filter effect, leading to fluorescence quenching. Meanwhile, under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), acetylcholine (ATCh) was decomposed to hydrogen peroxide (H2O2), which could destroy AgNPs to form Ag+ released from PCN-224 for fluorescence recovery. Instead, fenitrothion, an OPP, inhibited AChE activity, allowing the quenched fluorescence to be reactivated. Under the current optimum conditions, the fluorescence intensity had a good correlation (Y = -728.5370X + 2178.4248, R2 = 0.9869) over a dynamic range of fenitrothion concentrations from 0.1 to 500 ng/mL, with an LOD of 0.037 ng/mL. In addition, the anti-interference ability and robustness of the proposed sensor was verified for the monitoring of fenitrothion in tea with recoveries of 87.67-103.72% and the relative standard deviations (RSD) < 5.43%, indicating that the system has excellent prospects for OPP determination in practical applications. Furthermore, this work provides a universal platform for screening other enzyme inhibitors to detect OPPs.

Individual variation within wild populations of an arid-zone lizard dictates oxidative stress levels despite exposure to sublethal pesticides.

The relationship between sublethal pesticide exposure and oxidative stress in an ecologically relevant field setting is relatively unknown for reptiles. Oxidative stress is a multi-faceted concept that dictates key survival and fitness parameters in any organism. Fipronil and fenitrothion are two pesticides widely used globally for agricultural pest management. Using a field-based, BACI designed experiment we investigated the impact of sublethal pesticide exposure on oxidative stress biomarkers protein carbonyl and DNA damage (8-OHdG), in an arid-zone lizard species, Pogona vitticeps. A single ecologically relevant dose of pesticide was applied via oral gavage to treatment animals. Lizard condition, activity measures, and blood biomarkers were measured at relevant sampling intervals. Cholinesterase (ChE) and acetylcholinesterase (AChE) enzymatic biomarkers were measured in response to fenitrothion, and fipronil blood residues were measured for fipronil-treated lizards. Results suggested no significant treatment effect of either pesticide on parameters measured, however, 8-OHdG levels decreased by ≥ 45% for both pesticide treatment groups and not controls. Protein carbonyl levels showed a high degree of individual variation that proved more influential than pesticide exposure. Building our understanding of the macromolecular impacts of sublethal pesticide exposure on wild lizard populations is an integral step in addressing the current gap in literature and management practices. Our study has also highlighted the complex nature of studying oxidative stress in the field and the sheer necessity of future study.

Simultaneous electrochemical degradation of pesticides from the aqueous environment using Ti/SnO2-Sb2O3/PbO2/Bi electrode; process modeling and mechanism insight.

In this work, modified Bi-PbO2 electrode was fabricated and employed for simultaneous degradation of fenitrothion (FT), trifluralin (TF), and chlorothalonil (CT) from synthetic and pesticide wastewater through the anodic oxidation process. A novel high-performance liquid chromatography method was developed and optimized to identify the pesticides simultaneously. Quadratic models were developed to investigate the effects of main operating parameters and predict the degradation efficiencies of the treatment processes. The R2 of the degradation efficiencies were obtained of 0.9847, 0.9910, and 0.9821 for FT, TF, and CT, respectively, which indicates the degree of conformity between the experimental and the actual values of degradation efficiencies, and the adjusted R2 values for the degradation efficiency of FT, TF, and CT in proposed models were 0.9826, 0.9898, and 0.9796, and the values of the predicted R2 were 0.9792, 0.9875, and 0.9755, respectively. The maximum degradation efficiencies of 99.7, 100, and 100% obtained for FT, TF, and CT, respectively, under the optimal operating condition of FT, TF, and CT concentration of 10.0, 6.0, and 8.0 mg L-1, respectively, pH 6.0, the current density 6.0 mA cm-2, and electrolysis time of 60 min. Chemical oxygen demand removal and energy consumption were 64.7% and 5.1 kWh m-3. Eventually, the generated intermediates and other produced species of pesticides through the treatment process was evaluated using a gas chromatography-mass spectrometry method, and their degradation pathways were proposed.

Exposure to organophosphorus compounds of Japanese children and the indoor air quality in their residences.

Several organophosphorus compounds such as organophosphate pesticides (OPPs) and trialkylphosphates (TAPs) are suspected to inhibit cholinesterase activities, to affect endocrine systems or to possibly be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially in children, we measured the household exposure to OPPs and TAPs by Japanese children via all exposure pathways and the contribution of indoor air quality. First-morning void urine was collected from subjects aged 6 to 15 years (n = 132), and airborne organophosphorus compounds were sampled in the subject's bedroom for 24 h. Airborne levels of nine OPPs and three TAPs and their urinary metabolites were determined. No significant correlations were detected for any compounds between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The estimated daily intakes were as follows (median, µg/kg b.w./d): chlorpyrifos, 0.042; diazinon, 0.067; tri-n-butylphosphate, 0.094. The 95th percentiles of the intakes for fenthion, fenitrothion and the above three compounds did not exceed their reference limit values, although one subject had a daily intake of tri-n-butylphosphate that was about twice its reference limit value. The concentration levels of the urinary metabolite of tri-n-butylphosphate in our subjects tended to be higher than those for children in many other countries. The fractions of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways was only 2.3 % (median) for tri-n-butylphosphate. Inhalation did not seem to contribute very much as an absorption pathway of the organophosphorus compounds in these Japanese children while they were at home. The exposure amounts of OPPs were not suggested to be high enough to adversely affect the health of these children at present on the basis of their daily intakes compared to their reference limit values.

Ultrasonic stimulation of milk fermentation: effects on degradation of pesticides and physiochemical, antioxidant, and flavor properties of yogurt.

BACKGROUND: Ultrasound has the potential to increase microbial metabolic activity, so this study explored the stimulatory effect of ultrasound pre-treatment on the degradation of four common pesticides (fenitrothion, chlorpyrifos, profenofos, and dimethoate) during milk fermentation by Lactobacillus plantarum and its effect on yogurt quality. RESULTS: Appropriate ultrasound pretreatment significantly enhanced the growth of L. plantarum. The degradation percentages of pesticides increased by 19-38% under ultrasound treatment. Ultrasonic intensity, pulse duty cycle, and duration time were key factors affecting microbial growth and pesticide degradation. Under optimal ultrasonic pre-treatment conditions, the degradation rate constants of four pesticides were at least 3.4 times higher than those without sonication. In addition, such ultrasound pretreatment significantly shortened yogurt fermentation time, increased the water holding capacity, hardness and antioxidant activity of the yogurt, and improved the flavor quality of the yogurt. CONCLUSION: Ultrasonic pretreatment significantly accelerated the degradation of the four pesticides during yogurt fermentation. In addition, such ultrasound pretreatment increased the efficiency of yogurt making and improved the quality of yogurt in terms of water holding capacity, firmness, antioxidant activity, and flavor. These findings provide a basis for the application of ultrasound to the removal of pesticide residues and quality improvement of yogurt. © 2022 Society of Chemical Industry.

Facile synthesis disposable MOF membrane filter: Growth of NH2-MIL-125 (Ti) on filter paper for fast removal of organophosphorus pesticides in aqueous solution and vegetables.

Metal-organic frameworks (MOFs) have great potential to remove pesticide residues. However, the lack of affinity between the materials and target and the process of trivial sample preparation resulted in limited removal efficiency. Here, we report a one-pot method for the fast preparation of NH2-MIL-125 (Ti)-based filter paper to synthesise NH2-MIL-125 (Ti)-based filter paper membranes. The NH2-MIL-125 (Ti)-based filter paper membrane takes advantage of π-π interactions between the organophosphorus pesticides (OPPs) and the benzene ring of MOFs. The affinity of amino groups and metal Ti for phosphorus atoms in the OPPs exhibits rapid removal efficiency for three OPPs, imidan, fenthion, and fenitrothion. The isothermal adsorption results for imidan, fenthion, and fenitrothion were consistent with the Langmuir, Freundlich, and Langmuir models, respectively. The kinetic results for imidan, fenthion, and fenitrothion agreed with the pseudo-second-order kinetic model, and the removal efficiency reached equilibrium within 1 min. There was no significant change in the adsorption capacity of OPPs in different pH solutions (pH = 2-10). Compared with that of MOFs, the NH2-MIL-125 (Ti)-based filter paper membrane removal efficiency of OPPs is the same, and it also has better removal efficiency in actual spinach samples. As a result, the sample pretreatment procedure was simplified using a low-cost and simple-to-synthesize disposable NH2-MIL-125 (Ti)-based filter paper membrane, samples' quick separation and the simultaneous fast removal of OPPs.

Degradation of pesticides in wheat flour during noodle production and storage.

The fate of five pesticides comprising triadimefon, imidacloprid, fenitrothion, chlorpyrifos-methyl, and chlorpyrifos in wheat flour during noodle production and accelerated storage was systematically investigated. Pesticide residues were determined by high-performance liquid chromatography with diode array detection (HPLC-DAD) after each processing step and accelerated storage. The results indicated that dough mixing reduced the concentration of five pesticide residues by 23-42%, mainly owing to the increase of moisture content. Dough resting had little effect on the residues of triadimefon, imidacloprid, and fenitrothion, but decreased chlorpyrifos-methyl and chlorpyrifos significantly by 24% and 15%, respectively. The pesticide residues increased by 3% to 69% during the drying step, attributed to the different role played by thermal evaporation or thermal degradation and concentration of the different pesticides. Boiling lowered the pesticide residues significantly by 56% to 74% in both fresh noodles and dried noodles. All the pesticide residues decreased during accelerated storage, especially for fenitrothion, chlorpyrifos-methyl, and chlorpyrifos. The processing factors (PFs) of the five pesticides in the drying step were greater than 1, while the others were all less than 1. The whole process for noodle production was beneficial to reduce the pesticide residues with PFs ranging from 0.15 to 0.35. The PFs of five pesticides in accelerated storage were all below 1.

Contamination, dynamics, and health risk assessment of pesticides in seawater and marine samples from the Seto Inland Sea, Japan.

We assessed the contamination, dynamics, and health risks of the pesticides cyanazine, simetryn, fenarimol, isoprothiolane, diazinon, irgarol, fenitrothion, and diuron in marine samples (seawater, sediments, plankton, fish, and other edible organisms) at various locations in the Seto Inland Sea in Japan in 2016 and 2017. Pesticide concentrations were highest at sampling sites close to the coastline, and mean concentrations in seawater were slightly higher in surface water than in bottom water. All eight pesticides were detected in plankton. Diazinon concentrations (77-387 ng/g dw) were highest in sediments and cyanazine was the most frequently detected pesticide (88%, n = 17) in sediments. Only cyanazine (2.7-41.9 ng/g dw), simetryn (1.0-34.3 ng/g dw), and diazinon (6.3-308.8 ng/g dw) were detected in fish and other edible marine organisms. Based on the calculated bioconcentration factor, the results showed that plankton, fish, and marine animals bioaccumulated pesticides. The highest hazard quotients were calculated for diazinon in red seabream and greenling, indicating a possible risk to consumers. It is, therefore, imperative to promote strict implementation of pollution control, integrated pest management practices, and policy formulation on pesticides. Usage of diazinon must be controlled and monitored to ensure large residues do not reach aquatic ecosystems and marine coastlines.

Resveratrol alleviates cardiac apoptosis following exposure to fenitrothion by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway through pro-oxidant and inflammatory response improvements: In vivo and in silico studies.

Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1ß (IL1ß,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.

The ameliorative effect of curcumin on hepatic CYP1A1 and CYP1A2 genes dysregulation and hepatorenal damage induced by fenitrothion oral intoxication in male rats.

This research aimed to assess curcumin (CUR) effects on fenitrothion (FNT), a broad-spectrum organophosphate insecticide, -induced hepatorenal damage. Thirty adult male Wistar rats were allocated at random to five equal groups orally administered distilled water containing 1% carboxyl methylcellulose, corn oil (1 mL/rat), CUR (100 mg/kg b.wt.), FNT (5 mg/kg b.wt.), or CUR + FNT. CUR and FNT were dosed three times a week for two months. At the end of this trial, blood and tissue samples (liver and kidney) were subjected to molecular, biochemical, and histopathological assessments. The results revealed that CUR significantly diminished the FNT-induced up-regulation of hepatic CYP1A1 and CYP1A2 transcriptional levels. Moreover, CUR significantly suppressed the increment of the serum levels of hepatic alanine aminotransferase, gamma-glutamyl transferase, and kidney damage indicators (urea and creatinine) in FNT-intoxicated rats. Furthermore, in the hepatic and renal tissues, CUR remarkably restored the FNT-associated depletion of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase, and superoxide dismutase). In addition, CUR notably reduced the FNT-induced increment in malondialdehyde content in the hepatic and renal tissues. Besides, the pathological aberrations in liver and kidney tissues resulting from FNT exposure were significantly abolished in FNT + CUR treated rats. Overall, CUR could be an effective ameliorative agent against negative pesticide impacts like FNT.

Linseed ameliorates renal apoptosis in rat fetuses induced by single or combined exposure to diesel nanoparticles or fenitrothion by inhibiting transcriptional activation of p21/p53 and caspase-3/9 through pro-oxidant stimulus.

Gestational exposure to environmental pollutants can induce oxidative injury and apoptosis since the fetal organs are sensitively vulnerable to these chemicals. In this work, we have investigated the renal anti-apoptotic efficiency of linseed (LS) against the oxidative stress-mediated upregulation of the fetal apoptosis-related genes following the prenatal intoxication with diesel nanoparticles (DNPs) and/or fenitrothion (FNT). A fifty-six timed-pregnant rats were equally divided to eight groups; control, LS (20% in diet), DNPs (0.5 mg/kg by intratracheal inoculation), FNT (3.76 mg/kg by gavage), DNPs+FNT, LS + DNPs, LS + FNT, and LS + DNPs+FNT. The transmission electron microscope analysis revealed the spherical shape of diesel particles with a homogeneous nanosized range (20-92.3 nm) and the crystallinity was confirmed by electron diffraction microscopy. Administration of DNPs and/or FNT significantly increased fetal renal malondialdehyde, nitric oxide, and glutathione reductase as compared with the control group. However, they declined the level of glutathione together with the activities of glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase. Furthermore, DNPs and/or FNT elicited many histopathological changes in fetal renal cells, markedly up-regulated apoptosis-related gene expressions (p53, p21 caspase-3, and caspase-9), and evoked DNA breaks as detected by comet assay. Interestingly, LS supplementation significantly ameliorated the disturbances in oxidant/antioxidant biomarkers, downregulated the apoptosis gene expressions, and alleviated DNA damage alongside renal cell architecture. These findings reveal that the antioxidant and anti-apoptotic characteristics of LS are acceptable defender pointers for the renal injury especially during gestational exposure to DNPs and/or FNT.

Quercetin ameliorates the hepatic apoptosis of foetal rats induced by in utero exposure to fenitrothion via the transcriptional regulation of paraoxonase-1 and apoptosis-related genes.

BACKGROUND & PURPOSE: Exposure to organophosphorus during different phases of pregnancy induces many adverse impacts on the developing foetuses due to their immature detoxification system. We have estimated the potential amelioration role of quercetin against hepatic injury-induced apoptosis in rat foetuses following gestational exposure to fenitrothion and probable involvement of paraoxonase-1. METHODS: Forty pregnant rats were allocated into four groups; the first one kept as control, the second intubated with quercetin (100 mg/kg), the third orally administrated fenitrothion (4.62 mg/kg) and the last group received quercetin two hours before fenitrothion intoxication. RESULTS: Fenitrothion significantly elevated the foetal hepatic levels of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide, but it reduced the enzymatic activities of glutathione-S-transferase, superoxide dismutase, catalase, and acetylcholinesterase. Furthermore, fenitrothion provoked many histopathological changes in the foetal liver and markedly up-regulated the mRNA gene expression of p53, caspase-9 along with elevation in the immunoreactivity of Bax and caspase-3, but it down-regulated the expression level of paraoxonase-1. Remarkably, quercetin co-treatment successfully ameliorated the hepatic oxidative injury and apoptosis prompted by fenitrothion. CONCLUSIONS: Dietary supplements with quercetin can be used to reduce the risk from organophosphorus exposure probably through paraoxonase-1 up-regulation and enhancement of the cellular antioxidant system.

Optimization of reaction time for detection of organophosphorus pesticides by enzymatic inhibition assay and mathematical modeling of enzyme inhibition.

Enzyme inhibition assay was used as a biomarker for detection of organophosphates pesticides in food and environmental samples. The aim of the present study was to optimize the time of enzyme-inhibitor reaction for quantitative determination of fenitrothion organophosphate based on cholinesterase inhibition. The results showed that this method provides a time-efficient, best linearity and simple assay. The effect of reaction time on the linearity relationship of the noncompetitive inhibition equation was studied. The best linearity of the assay was found at an optimum reaction time of 3.0 min, with coefficient of determination r 2 of 0.9972, in the range of inhibitor concentrations from 0.016 to 2.0 µg mL-1. The enzyme inhibition reached a plateau at 5 min by addition of pesticide in vitro and then the inhibited enzyme reactivate spontaneously and approached steady state at 20 min. A theoretical kinetic model to explain the effect of reaction time on the enzyme inhibition by addition of pesticide in vitro was derived. The higher values of coefficient of determination r 2 for the predicted model and error functions of the minimum deviations suggest that this model can be used to represent the experimental data and explain the plasma cholinesterase inhibition by fenitrothion pesticide.

Cloisite Microrobots as Self-Propelling Cleaners for Fast and Efficient Removal of Improvised Organophosphate Nerve Agents.

Naturally available microclays are well-known materials with great adsorption capabilities that are available in nature in megatons quantities. On the contrary, artificial nanostructures are often available at high cost via precision manufacturing. Such precision nanomanufacturing is also typically used for fabrication of self-propelled micromotors and nanomachines. Herein, we utilized naturally available Cloisite microclays to fabricate autonomous self-propelled microrobots and demonstrated their excellent performances in pesticide removal due to their excellent adsorption capability. Six different modified Cloisite microrobots were investigated by sputtering their microclays with platinum (Pt) for the fabrication of platinum-Cloisite (Pt-C) microrobots. The obtained microrobots displayed fast velocities (v > 110 µm/s) with fast and efficient enhanced removal of the pesticide fenitrothion, which is also considered as improvised nerve agent. The fabricated Pt-C microrobots exhibited low cytotoxicity even at high concentrations when incubated with human lung carcinoma epithelial cells, which make them safe for human handling.

Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine.

N-acetylcysteine (NAC) has largely been used as an effective chemo- protective agent owing to their beneficial effect in restoring several physiological parameters and relieving oxidative stress. Interestingly, it has been suggested that NAC mechanisms of action extend beyond being a precursor to the antioxidant glutathione and that they may involve several neurotropic and inflammatory pathways. Exposure to fenitrothion, an organophosphorus insecticide, promotes oxidative stress and induces several deleterious changes in the immune response and various tissues including cerebrum and spleen. The main objective of our study was to investigate ameliorative efficacy of N-acetylcysteine for immunological and neurological alterations and oxidative DNA damage induced by fenitrothion toxicity in cerebrum and spleen tissues of male rats. Our results revealed that oral exposure to fenitrothion for 30 days caused a reduction in the erythrocyte count in addition to leukocytosis, lymphocytosis, and neutrophilia. Also, this route of administration increased the serum levels of LDH, TNF-α, and IL-2 with reduction in serum immunoglobulins (IgG & IgM) concentrations. Furthermore, a significant downregulation in the antioxidant markers (GSH & SOD) with an elevation of free radical (MDA) levels were noticed. Regarding the brain, fenitrothion administration inhibited AchE activity and increased brain GABA, serotonin and dopamine levels. Moreover, it induced an elevation in oxidative DNA damage indicated by 8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine co-treatment restored the normal physiological tone in most of these parameters. Immunostaining for GFAP and Caspase-3 markers in the brain and spleen tissues were increased respectively. In conclusion, N-acetylcysteine supplementation has an ameliorative effect against immunotoxic, neurotoxic and oxidative DNA damage induced by fenitrothion exposure.

Protective effect of N-acetylcysteine on fenitrothion-induced toxicity: The antioxidant status and metabolizing enzymes expression in rats.

The existence of fenitrothion (FNT) in the soil, water, and food products has harmful effects on non-target organisms. Therefore, this study was conducted to evaluate the hepatotoxic, nephrotoxic and neurotoxic effects of FNT and the possible ameliorative effect of N-acetylcysteine (NAC), a precursor of intracellular GSH, on FNT-induced toxicity. For this purpose, thirty-two adult male albino rats were allocated into control group and groups treated with NAC (200 mg/kg), FNT (10 mg/kg) and FNT + NAC via gastric tube daily for 28 days. FNT intoxication significantly reduced food intake, water intake, body weight, and body weight gain and altered the expression of phase I and phase II xenobiotic-metabolizing enzymes-cytochrome P450 (CYP1A1) and glutathione S-transferase (GSTA4-4). In hepatic, renal and brain tissues, FNT induced oxidative stress, hepatopathy, nephropathy, and encephalopathy, and significantly increased pro-inflammatory cytokines. Furthermore, FNT exposure significantly elevated the level of hepatic and renal injury biomarkers and significantly inhibited the brain acetylcholinesterase activity. Co-administration of NAC with FNT modulated most of these altered biochemical, oxidative and inflammatory markers and restored the xenobiotic-metabolizing enzymes expression and histological structures. Our study indicated the involvement of oxidative damage, inflammation, and alteration of xenobiotic-metabolizing enzymes expression in FNT-induced toxicity and revealed that they were significantly improved by NAC co-treatment. These findings suggest that NAC administration might protect against FNT-induced toxicity in non-target organisms, including humans.

Walnut Polyphenol Extract Protects against Fenitrothion-Induced Immunotoxicity in Murine Splenic Lymphocytes.

Fenitrothion (FNT), an organophosphate pesticide, exerts an immunotoxic effect on splenocytes. Dietary polyphenol compounds exert antioxidant, anticancer and antihypertensive effects. In this study, we investigated the effect of walnut polyphenol extract (WPE) on FNT-induced immunotoxicity in splenic lymphocytes in vitro. Treatment with WPE significantly increased the proliferation of FNT-exposed splenocytes, as evidenced by increases in the proportions of splenic T lymphocytes (CD3⁺ T cells) and T-cell subsets (CD8⁺ T cells), as well as the secretion of the T-cell-related cytokines interleukin (IL)-2, interferon-γ, IL-4 and granzyme B. These effects were associated with a reduction in oxidative stress, as evidenced by changes in the levels of hydroxyl radical, superoxide dismutase, glutathione peroxidase and malondialdehyde. Moreover, WPE decreased the FNT-induced overexpression of NADPH oxidase 2 and dual oxidase 1 by regulating Toll-like receptor 4 signaling in splenic T-cells. Taken together, these findings suggest that WPE protects against FNT-mediated immunotoxicity and improves immune function by inhibiting oxidative stress.