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PloS One 2014The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the...
The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics.
Topics: Biocatalysis; Brain; Cell Line, Tumor; Cytochrome P-450 Enzyme System; Gene Expression Regulation, Enzymologic; Humans; Molecular Docking Simulation; Monocrotophos; Neurotoxins; Protein Conformation; Transcription, Genetic; Xenobiotics
PubMed: 24663500
DOI: 10.1371/journal.pone.0091946 -
Paediatrics and International Child... May 2022Munchausen syndrome by proxy is a form of abuse in which an adult, usually the mother, deceives health workers by exaggerating, falsifying or directly inducing...
Munchausen syndrome by proxy is a form of abuse in which an adult, usually the mother, deceives health workers by exaggerating, falsifying or directly inducing psychological or physical symptoms in the child victim for psychological gratification. In 2013, the American Academy of Pediatrics coined the term 'caregiver-fabricated illness in a child' to describe this form of child abuse. A 7-year-old girl had many encounters with health workers over a period of 4 years and presented with evolving clinical features including refractory seizures and red urine for which she was followed up as a case of acute intermittent porphyria. She was later discovered to be the victim of chronic monocrotophos organophosphate poisoning by her mother. If all medical staff who manage children are to avoid becoming inadvertent participants in medical child abuse, this case report is an important reminder that a high index of suspicion is warranted in cases which present a diagnostic dilemma and who respond unexpectedly to treatment. AIP: Acute intermittent porphyria; APSAC: American Professional Society on the Abuse of Children; ASM: anti-seizure medication; CFIC: caregiver-fabricated illness in a child; CT: computed tomography: DVT: deep vein thrombosis; EEG: electroencephalogram: ESR: erythrocyte sedimentation rate; HDW: high-dependency ward; ICU: intensive care unit; LFT: liver function test; MBP: Munchausen syndrome by proxy; NICU: neonatal intensive care unit; RFT: renal function test; TB: Tuberculosis; UTH-CH: University Teaching Hospitals Children's Hospital.
Topics: Adult; Anistreplase; Child; Female; Humans; Infant, Newborn; Insecticides; Monocrotophos; Mothers; Munchausen Syndrome by Proxy; Organophosphate Poisoning; Porphyria, Acute Intermittent
PubMed: 35938355
DOI: 10.1080/20469047.2022.2108671 -
Neurotoxicology Sep 2017Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known...
Monocrotophos, an organophosphorus insecticide, disrupts the expression of HpNetrin and its receptor neogenin during early development in the sea urchin (Hemicentrotus pulcherrimus).
Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0.01, 0.10, and 1.00mg/L MCP. The results showed that MCP disrupted HpNetrin and neogenin expression at different developmental stages in H. pulcherrimus and that Ca appeared to be involved in the MCP-induced developmental neurotoxicity. Specifically, the lower concentrations of MCP elevated HpNetrin and neogenin transcription, resulting in higher intracellular Ca levels during the early developmental stages in the sea urchin; this may affect netrin-directed cell migration/axon extension and subsequently disrupt serotonergic axon branching and synapse formation. In contrast, 1.00mg/L MCP exhibited an inhibitory effect on HpNetrin and neogenin transcription. This finding implies that the regulatory roles of these factors may be diminished during early development, thereby causing developmental defects in the sea urchin. Collectively, our results provide a basis for exploring the involvement of netrin and neogenin in the organophosphate-induced disruption of the SNS during development.
Topics: Actins; Age Factors; Animals; Calcium; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Insecticides; Larva; Membrane Proteins; Monocrotophos; Netrins; RNA, Messenger; RNA, Ribosomal, 18S; Sea Urchins
PubMed: 28645554
DOI: 10.1016/j.neuro.2017.06.010 -
Analytical and Bioanalytical Chemistry Sep 2014The present study on in vitro formation and characterization of lysozyme adduct with monocrotophos (MP) evaluates the potential of lysozyme to be used as a sensitive...
The present study on in vitro formation and characterization of lysozyme adduct with monocrotophos (MP) evaluates the potential of lysozyme to be used as a sensitive biomarker to monitor exposure levels to the commonly used organophosphorus pesticide monocrotophos. Crystallization of lysozyme protein adduct with monocrotophos was also undertaken to understand the adduct formation mechanism at a molecular level. The binding of organophosphorus pesticides to lysozyme is one of the key steps in their mutagenicity. The formation and structural characterization of lysozyme adduct with monocrotophos was done using MALDI-TOFMS, fluorescence, UV/Vis spectroscopy, circular dichroism, and X-ray diffraction studies. We report the crystal structure of lysozyme adduct with monocrotophos at 1.9 Å. It crystallized in the P43 space group with two monomers in one asymmetric unit having one molecule of monocrotophos bound to each protein chain. The results proved that the fluorescence quenching of lysozyme by monocrotophos is due to binding of monocrotophos with a tryptophan residue of lysozyme. Monocrotophos interacts most strongly with the Trp-108 and Asp-52 of lysozyme. The interactions of the monocrotophos molecule with the lysozyme suggest the formation of a stable adduct. In addition, the alteration of lysozyme secondary structure in the presence of monocrotophos was confirmed by circular dichroism and fluorescence inhibition of lysozyme by increasing monocrotophos and UV/Vis spectrophotometry. The formation of lysozyme adduct with monocrotophos was confirmed by MALDI-TOFMS.
Topics: Animals; Binding Sites; Biomarkers; Buffers; Chickens; Circular Dichroism; Humans; Hydrogen-Ion Concentration; Monocrotophos; Muramidase; Pesticides; Protein Binding; Protein Structure, Secondary; Spectrometry, Fluorescence; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrophotometry, Ultraviolet; Tryptophan; X-Ray Diffraction
PubMed: 24969463
DOI: 10.1007/s00216-014-7953-y -
Journal of Applied Toxicology : JAT Jun 2017The present study aimed to obtain insights into the mechanism(s) by which glucose-rich diet aggravates monocrotophos (MCP)-induced dopaminergic neuronal dysfunction in...
The present study aimed to obtain insights into the mechanism(s) by which glucose-rich diet aggravates monocrotophos (MCP)-induced dopaminergic neuronal dysfunction in Caenorhabditis elegans. In this study, we exposed three different strains of worms (wild-type N2, CB1112 (cat-2(e1112)II, tyrosine hydroxylase-deficient mutant, catecholamine absent) and the transgenic BZ555 (egls1-dat-1p::green fluorescent protein [GFP]) (in which bright GFP is tagged to the dopamine neuronal soma and processes) grown and maintained in normal nematode growth medium or 2% glucose enriched-nematode growth medium to MCP (0.75 mm) for 48 h. After the exposure, dopamine-mediated behaviors such as repulsion to nonanone, chemotaxis index and basal slowing response were determined in worms. Dopamine, 3,4-dihydroxy phenyl acetic acid and homovanillic acid content were quantified in N2 worms. The extent of neurodegeneration was visualized and quantified in dat-1::GFP worms. Basal slowing response study clearly indicated that cat-2 worms exposed to MCP and glucose were less affected compared to N2 of the same treatment. Learning and memory were affected by MCP and glucose. While MCP-treated worms showed lesser repulsion to nonanone compared to control worms, MCP-treated, glucose-fed worms showed a greater reduction in repulsion to nonanone. Further, MCP-treated, glucose-fed worms exhibited a marked reduction in dopamine content and an increase in 3,4-dihydroxy phenyl acetic acid and homovanillic acid levels compared to that in control. Dat-1::GFP showed a significant degeneration of dopaminergic neurons when exposed to glucose and MCP. Thus, our results clearly demonstrate that glucose-rich diet aggravates the dopaminergic neuronal dysfunction induced by MCP in C. elegans. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Animals; Animals, Genetically Modified; Behavior, Animal; Caenorhabditis elegans; Catalase; Catecholamines; Diet; Dopamine; Dopaminergic Neurons; Glucose; Green Fluorescent Proteins; Microscopy, Confocal; Microscopy, Fluorescence; Monocrotophos
PubMed: 27995639
DOI: 10.1002/jat.3426 -
Antioxidants (Basel, Switzerland) Dec 2021Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective,...
Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective, anti-inflammatory and antiapoptotic properties. The present study evaluated the effect of -acetylcysteine (NAC) against monocrotophos (MCP) exposure-induced toxicity in the rat liver. Albino Wistar rats were divided into four groups: (1) control, (2) NAC-treated, (3) MCP-exposure, (4) NAC and MCP-coexposure group. The dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) were administered orally for 28 days. Exposure to MCP caused a significant increase in lipid peroxidation, protein oxidation and decreased glutathione content along with the depletion of antioxidant enzyme activities. Further MCP exposure increased pro-inflammatory cytokines levels and upregulated Bax and Caspase-3 expressions. MCP exposure also caused an array of structural alternations in liver tissue, as depicted by the histological and electron microscopic analysis. Thepretreatment of NAC improved glutathione content, restored antioxidant enzyme activities, prevented oxidation of lipids and proteins, decreased pro-inflammatory cytokines levels and normalized apoptotic protein expression. Treatment of NAC also prevented histological and ultrastructural alternations. Thus, the study represents the therapeutic efficacy and antioxidant potential of NAC against MCP exposure in the rat liver.
PubMed: 35052593
DOI: 10.3390/antiox11010090 -
Toxicology May 2013The morbidity and mortality rate of cardiovascular diseases are increasing massively worldwide. The environmental pollutants especially agrochemicals are the most...
The morbidity and mortality rate of cardiovascular diseases are increasing massively worldwide. The environmental pollutants especially agrochemicals are the most unrecognized cardiovascular risk factors. Monocrotophos (MCP), an organophosphate pesticide with acetylcholine esterase inhibition activity is widely used in India and other parts of the world. The present study investigated the cardiotoxicity of prolonged intake of MCP. Wistar rats were administered 1/50th of LD50 dosage of MCP (0.36mg/kg body weight) orally via gavage daily for three weeks. MCP administered animals exhibited mild-hyperglycemia and dyslipidemia in blood. Cardiac oxidative stress was conferred by accumulation of protein carbonyls, lipid peroxidation and glutathione production. The cardiac markers (cTn-I, CK-MB and LDH) were showed elevated expression in blood plasma, which signals the cardiac tissue damage. The histopathology of the heart tissue authenticated the MCP induced tissue damage by showing signs of nonspecific inflammatory changes and oedema between muscle fibres. Thus the findings of this preliminary study illustrate the cardiotoxic effect of prolonged MCP intake in rats and suggest that MCP can be a possible independent and potent environmental cardiovascular risk factor.
Topics: Animals; Blood Glucose; Cardiomyopathies; Cardiotoxins; Creatine Kinase; Female; Glutathione; Heart; L-Lactate Dehydrogenase; Monocrotophos; Myocardium; Oxidative Stress; Pesticides; Rats; Rats, Wistar; Troponin I
PubMed: 23228476
DOI: 10.1016/j.tox.2012.11.022 -
Chemosphere May 2022The use of plastics has increased significantly with consequent rise in the generation of wastes. Microplastics (MPs) with particle size <5 mm are produced in natural...
The use of plastics has increased significantly with consequent rise in the generation of wastes. Microplastics (MPs) with particle size <5 mm are produced in natural terrestrial habitats by weathering of the discarded plastic debris and therefore are likely to impact soil biota. Earthworms are the dominant soil fauna which play vital role in soil formation and decomposition of organics. Since these animals are soil feeders, MP particles contaminating soil are likely to enter in to the gut of these animals affecting their physiology. MPs have been shown to be potent adsorbents of various other pollutants such as heavy metals and agrochemicals. This study reports the effects of two MPs, polyvinyl chloride (PVC) and polypropylene (PP) alone and in combination with the pesticide monocrotophos in soil on tissue protein, lipid peroxidation (LPX), activities of lactate dehydrogenase (LDH) and catalase (CAT) of an epigeic earthworm Eudrillus eugeniae over an exposure period of 48h. Results from molecular docking and laboratory experiment confirmed that both the MPs are potent adsorbents of the pesticide and enhanced oxidative stress on the animal with significant reduction in protein, increased LPX level and enzyme activities. PP indicated significantly higher pesticide adsorption relative to PVC.
Topics: Animals; Annelida; Molecular Docking Simulation; Monocrotophos; Oxidative Stress; Pesticides; Plastics; Polypropylenes; Polyvinyl Chloride; Soil; Soil Pollutants
PubMed: 35120958
DOI: 10.1016/j.chemosphere.2022.133837 -
Environmental Science and Pollution... Feb 2018The bacterial strain Sphingobium sp. YW16, which is capable of degrading monocrotophos, was isolated from paddy soil in China. Strain YW16 could hydrolyze monocrotophos...
The bacterial strain Sphingobium sp. YW16, which is capable of degrading monocrotophos, was isolated from paddy soil in China. Strain YW16 could hydrolyze monocrotophos to dimethylphosphate and N-methylacetoacetamide and utilize dimethylphosphate as the sole carbon source but could not utilize N-methylacetoacetamide. Strain YW16 also had the ability to hydrolyze other organophosphate pesticides. A fragment (7067 bp) that included the organophosphorus hydrolase gene, opdA, was acquired from strain YW16 using the shotgun technique combined with SEFA-PCR. Its sequence illustrated that opdA was included in TnopdA, which consisted of a transpose gene, a putative integrase gene, a putative ATP-binding protein gene, and opdA. Additionally, a conjugal transfer protein gene, traI, was located downstream of TnopdA. The juxtaposition of TnopdA with TraI suggests that opdA may be transferred from strain YW16 to other bacteria through conjugation. OpdA was able to hydrolyze a wide range of organophosphate pesticides, with the hydrolysis efficiency decreasing as follows: methyl parathion > fenitrothion > phoxim > dichlorvos > ethyl parathion > trichlorfon > triazophos > chlorpyrifos > monocrotophos > diazinon. This work provides the first report of opdA in the genus Sphingobium.
Topics: Bacterial Proteins; Biodegradation, Environmental; China; Cloning, Molecular; DNA Transposable Elements; Hydrolysis; Mixed Function Oxygenases; Monocrotophos; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soil Microbiology; Soil Pollutants; Sphingomonadaceae
PubMed: 29204940
DOI: 10.1007/s11356-017-0718-3 -
Chemosphere May 2019The main aim of this study is to investigate the toxicity of organophosphate (OPs) insecticides monocrotophos (MCP) and chlorpyrifos (CLS) on plant growth promoting...
The main aim of this study is to investigate the toxicity of organophosphate (OPs) insecticides monocrotophos (MCP) and chlorpyrifos (CLS) on plant growth promoting (PGP) properties and seed germination of brinjal, tomato and okra vegetables inoculated by Microbacterium hydrocarbonoxydans (BHUJP-P1), Stenotrophomonas rhizophila (BHUJP-P2), Bacillus licheniformis (BHUJP-P3) and Bacillus cereus (BHUJP-P4). Maximum increase in microbial growth (52.6% & 47.9%) with enhanced EPS production (447.67 mg/ml & 75.00 mg/ml) was showed by BHUJP-P4 and BHUJP-P3 at 10× dose of MCP and CLS over control, BHUJP-2 and BHUJP-P1 respectively. Simultaneously, both strains recorded minimum reduction in PGP activities and seed germination at 3× dose of both insecticides as compared to BHUJP-2 and BHUJP-P1, respectively. Strains BHUJP-P3 and BHUJP-P4 showed 83 and 81% of monocrotophos degradation at 50 mg/kg concentration; 81 and 80% at 150 mg/kg concentration within 5days respectively. Concurrently, these strains BHUJP-P3 and BHUJP-P4 were recorded 53 and 90% of chlorpyrifos degradation at 50 mg/kg concentration; 49% and 87% at 100 mg/kg concentration within 72 h, respectively. The OPs insecticide degrading gene opdA and opd was found in strain BHUJP-P3 and BHUJP-P4, respectively. The multifarious biological activities of strain BHUJP-P3 and BHUJP-P4 showed maximum tolerance against insecticide, and minimum reduction in P-solubilisation, IAA, siderophore and HCN production for plant growth promotion and biological control under insecticide stress. Thus, these novel isolates may be used as biodegradation of organophosphate insecticide and plant growth promoting bacterial (PGPB) inoculum for enhancing seed germination of vegetables under stress insecticide. These novel strains will be environment friendly, socially acceptable and economically viable.
Topics: Biodegradation, Environmental; Chlorpyrifos; Germination; Monocrotophos; Soil Microbiology; Vegetables
PubMed: 30798059
DOI: 10.1016/j.chemosphere.2019.02.053