Amelioration of Hepatotoxic and Neurotoxic Effect of Cartap by Aloe vera in Wistar Rats.

Pesticide exposure can pose a serious risk to nontarget animals. Cartap is being broadly used in agricultural fields. The toxic effects of cartap on the levels of hepatotoxicity and neurotoxicity have not been properly studied in mammalian systems. Therefore, the present work focused on the effect of cartap on the liver and brain of Wistar rats and made an assessment of the ameliorating potential of A. vera. The experimental animals were divided into 4 groups, comprising six rats in each: Group 1-Control; Group 2-A. vera; Group 3-Cartap; and Group 4-A. vera + Cartap. The animals orally given cartap and A. vera were sacrificed after 24 h of the final treatment and histological and biochemical investigations were conducted in liver and brain of Wistar rats. Cartap at sublethal concentrations caused substantial decreases in CAT, SOD, and GST levels in the experimental rats. The activity levels of transaminases and phosphatases in cartap group were also found to be substantially altered. The AChE activity was recorded as decreasing in RBC membrane and brain of the cartap-treated animals. The TNF-α and IL-6 level in serum were increased expressively in the cartap challenged groups. Histological investigation of liver showed disorganized hepatic cords and severely congested central veins due to cartap. However, the A. vera extract was observed to significantly protect against the effects of cartap toxicity. The protective impact of A. vera against cartap toxicity may be due to the existence of antioxidants in it. These findings suggest that A. vera may be developed as a potential supplement to the appropriate medication in the treatment of cartap toxicity.

Flow injection chemiluminescence determination of acetochlor and cartap-HCl in freshwater samples using an acidic KMnO4 -rhodamine-B reaction system.

A flow injection (FI) methodology using the acidic potassium permanganate (KMnO4 )-rhodamine-B (Rh-B) reaction with chemiluminescence (CL) detection was established to determine acetochlor and cartap-HCl pesticides in freshwater samples. Experimental parameters were optimized, and Chelex-100 cationic exchanger mini column and solid-phase extraction (SPE) were used as phase separation techniques. Linear calibration curves were observed for the standard solutions of acetochlor and cartap-HCl over the ranges 0.005-2.0 mg L-1 [y = 1155.8x + 57.551, R2  = 0.9999 (n = 8)] and 0.005-1.0 mg L-1 [y = 979.76x + 14.491, R2  = 0.9998 (n = 8)] with LODs and LOQs of 7.5 × 10-4 and 8.0 × 10-4  mg L-1 (3σ blank) and 2.5 × 10-3 and 2.7 × 10-3  mg L-1 (10σ blank), respectively, with an injection throughput of 140 h-1 . These methods were used to estimate acetochlor and cartap-HCl with or without the SPE procedure, respectively, in spiked freshwater samples. Results obtained were not significantly different at a 95% confidence level to those of other reported methods. Recoveries for acetochlor and cartap-HCl were obtained over the ranges 93-112% (RSD = 1.9-3.6%) and 98-109% (RSD = 1.7-3.8%), respectively. The most probable CL reaction mechanism was explored.

High-precision luminescent covalent organic frameworks with sp2-carbon connection for visual detecting of nereistoxin-related insecticide.

A new strategy for nereistoxin-related insecticide, cartap, detection in foodstuff and the environment is of great importance due to its poisoning of human beings through direct exposure or via biomagnification. Herein, a highly planar conjugated sp2 carbon-connected COF (F-Csp2-TT) was synthesized via Knoevenagel condensation reaction followed by the post-modification to develop a new platform for cartap visual detection in agricultural and food samples. The synergistic effect of highly planar conjugation and dense functional groups in the opened framework endowed F-Csp2-TT with a high-precision luminescence sensing performance. Meanwhile, the exquisitely designed F-Csp2-TT presented robust chemical stability, radiation stability, and good reproducibility. Benefiting from these advantages, high-precision luminescent F-Csp2-TT achieves a low detection limit of 0.51 µg/L to cartap over the range of 1-300 µg/L (R2=0.9938), and the recoveries percentage in food products was calculated as 95.90%- 119.3%. More significantly, the smartphone-based high-precision platform by F-Csp2-TT was established and successfully applied to portable monitoring of cartap and water content. Therefore, our work revealed the enormous potential of Csp2-connected COF, which opened a new situation for insecticide detection.

Ameliorative Impact of Aloe vera on Cartap Mediated Toxicity in the Brain of Wistar Rats.

Exposure to pesticides can pose a greater threat to multiple organs of nontarget animals. Cartap is a thiocarbamate pesticide, broadly used in agricultural fields. The assessment of neurotoxicity of cartap has not been properly studied in the mammalian systems. The present investigation unveils the toxic effects of cartap in the brain of Wistar rats its amelioration by using aqueous extract of Aloe vera leaves. We have used 4 groups of animals comprising six in each: Group 1- control, Group 2- control with Aloe vera, Group 3- cartap, Group 4- cartap with Aloe vera treated. After 15 days of treatment, biochemical investigations were conducted. Wistar rats orally exposed to sublethal doses of cartap, showed significant variations in the levels of prooxidants i.e. MDA and GSH (an oxidative stress marker) and enzymatic antioxidants i.e. SOD, CAT, GST, GPx. The decreased levels of CAT, SOD, GST and increased levels of GPx were detected in the experimental rats treated with cartap. The significant alterations were recorded with the declined activities of LDH and AChE, considered as the biomarker of energy metabolism and altered cholinergic function, respectively. However, the pre-administration of aqueous extract of Aloe vera leaves was found to markedly ameliorate the toxic effects of cartap by shielding the levels of aforesaid oxidative markers near to the control. The ameliorative impact of Aloe vera, might be due to the presence of several antioxidant molecules in it which were able to counter the oxidative stress generated by cartap stress. These results suggested that Aloe vera could be utilized as a possible supplement with the relevant therapeutics in the suitable management of cartap toxicity in association.

Insight into electrochemical degradation of Cartap (in Padan 95SP) by boron-doped diamond electrode: kinetic and effect of water matrices.

In this work, the kinetic electrochemical degradation of Cartap (CT) (in Padan 95 SP) at boron-doped diamond (BDD) electrode was investigated. This study indicated that the degradation of CT underwent both direct and indirect oxidations. Water matrices can either accelerate or inhibit the removal efficiency of CT: adding 15 mM Cl- improved kCT from 0.039 min-1 to 0.054 min-1 (increased by 38%), while kCT decreased by 61.5% and 64% when increasing the concentration of HCO3- and humic acid (HA) to 15 mM and 15 mg L-1, respectively. CT degradation was inhibited in the presence of methanol (MeOH) and tert-butanol (TBA) due to the scavenging effect of those chemicals toward reactive species. The contribution of reactive oxidants was calculated as: DET (direct electron transfer) accounted for 15%; •OH accounted for 61.5%; SO4•- accounted for 12.8%; ROS (the other reactive oxygen species) accounted for 8.5%. The transformation pathways of major reactive species were established.

Development, optimization, and validation of a method for detection of cartap, thiocyclam, thiosultap-monosodium, and thiosultap-disodium residues in plant foods by GC-ECD.

A method was developed for the simultaneous determination of four nereistoxin-related pesticides, viz. cartap, thiocyclam, thiosultap-monosodium, and thiosultap-disodium, in 20 plant foods. The samples were extracted using a hydrochloric acid solution containing cysteine hydrochloride, derivatized to nereistoxin under alkaline conditions, and analyzed by gas chromatography with electron capture detector. The average recoveries of the method were 72-108%, with relative standard deviations (RSDs) of 0.3-14.7% (n = 1200, p < 0.05). The intermediate precision and reproducibility experiments using established methods were also carried out. All the results passed the Cochrane and Grubbs tests (n = 2400, p < 0.05). The RSDs of intermediate precision and RSDs of reproducibility among laboratories were in the ranges 1.7-10.9% and 2.4-15.3% (n = 2400, p < 0.05), respectively, indicating that the accuracy and precision of the method are satisfactory. This method can be used to detect nereistoxin-related pesticides in plant foods.

Cartap hydrochloride induced stress response in Anabaena variabilis ARM 441.

Cartap hydrochloride is a moderately hazardous nereistoxin analogue insecticide that is predominantly applied in paddy fields of India, at a recommended dose of 10 µg ml-1 to kill chewing and sucking insect pests of rice crop. Toxicity of cartap hydrochloride was studied on non-target free-living nitrogen fixing cyanobacterium Anabaena variabilis ARM 441 commonly used as algal biofertilizer in rice cultivation. Anabaena sp. could tolerate commercial grade insecticide up to 30 µg ml-1. However, at the recommended dose of 10 µg ml-1, it caused reduction in algal growth, total nitrogen and heterocyst frequency by 47.28, 24.29 and 17.72% respectively, as well as photosynthetic pigments under pure culture conditions. Scanning electron micrographs revealed cell rupture and breakage in filaments due to cartap exposure with the formation of akinetes. Cartap hydrochloride induced stress, since level of superoxide dismutase, peroxidase and catalase were increased by 108.57, 187.5 and 117% respectively. Generation of superoxide radicals and hydrogen peroxide were also increased by 152.48 and 34% respectively. Lipid peroxidation was increased by 31.03%, whereas there was decline in ascorbate content by 48.45%, however the glutathione content was increased by 128.57%. Increase in osmolytes such as proline from 8.6 to 32.8% and sucrose from 61.22 to 90.13% indicates their possible role in overcoming cartap induced oxidative stress and can be helpful in assessing its detrimental effect on Anabaena variabilis ARM 441, since cyanobacterial biofertilizers are purposely used in paddy fields as nitrogen contributors.

Photolysis kinetics of cartap and nereistoxin in water and tea beverages under irradiation of simulated sunlight and ultraviolet under laboratory conditions.

Cartap applied widely in agricultural crops and tea plants is readily degraded into nereistoxin, resulting in a longer residual period and higher exposure risk to humans. The photolysis kinetics of cartap and nereistoxin in water and tea beverages was firstly investigated to explore the effect and mechanism of pesticide residue removal. Cartap and nereistoxin could be effectively photolyzed by ultraviolet and their photolysis rate increased with light intensity increasing. The photolysis percentage of cartap and nereistoxin in different solutions under ultraviolet irradiation of 200 W mercury lamp reached 81.8%-100.0% within 6 h. Relative to water solution, the water-soluble components in tea had an inhibition effect on the photodegradation of cartap and nereistoxin. This research provided a reference for the development of effective methods for the removal of cartap and its metabolite in water and tea beverages.

Studies on oral subacute toxicity of cartap in male mice.

S-[3-carbamoylsulfanyl-2-(dimethylamino)propyl] carbamothioate (Cartap) (CAS number: 15263-52-2) is a synthetic insecticide of thiocarbamates group that is extensively used in field of agriculture for controlling of several pests like rice stem borer, leaf folder pests in paddy field and diamond back moth, aphids in cabbage and cauliflower crops. Cartap, as a pesticide has not been investigated yet for its effect on vital organs and biochemical stress in vivo and the present study was undertaken to evaluate the same in Swiss albino mice. For this purpose male mice were given three different dose levels of cartap, i.e. 5 mg/kg, 7.5 mg/kg and 15 mg/kg body weight respectively, for 28 days orally. Water was used as vehicle to dissolve cartap. Oral administration of cartap caused significant increase in serum biomarkers, tissue oxidants and decrease in antioxidants along with histopathological findings in liver, kidney and brain tissues. Thus, present study showed that in vivo exposure to cartap induces tissue damage probably via oxidative stress in important vital organs of mice.

Kinetic characterization of rat brain acetylcholinesterase modulated by lead and cartap: the ameliorative effect of Citrus limon fruit juice.

OBJECTIVES: Human exposure to heavy metals and pesticides is a worldwide major health problem. These environmental pollutants have been considered as the most neurotoxic agents and responsible to causing neurological toxicity. Plant-based therapeutic supplement may be used in the event of toxicity. Citrus limon contains several useful bioactive ingredients including flavonoids, dietary fiber, carotenoids, vitamins, pectin, minerals, and essential oils, which are responsible for its therapeutic potential. In the present investigation, we have studied the toxicity of heavy metals such as lead (Pb) and a carbamate pesticide such as cartap (Cp) on rat brain acetylcholinesterase (AChE). METHODS: The chemical characterization of C. limon involved determination of total antioxidants and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging activity using known methods. The AChE activity and its kinetic characterization were performed by assaying the enzyme activity at varying substrate concentrations, pH, temperature, and time of reaction. Its different kinetic parameters such as K i , V max, K m , K cat, and K cat/K m were determined by using standard procedures. The amelioration potential of the extract was evaluated on the neurotransmission system of rat brain AChE treated with Pb, Cp, and their combination (Pb-Cp), considering their 50% inhibitory concentration (IC50) values. RESULTS: The optimal activity of rat brain AChE was recorded at 25 µg of protein, pH of 7.4, substrate concentration [S] of 0.5 mM, and temperature of 37.4-40°C. The enzyme was stable for 10 min when incubated at 37.4 °C in vitro. The enzyme displayed 70% of its activity remaining even after 160 min of incubation in this condition. It may be stable up to 1 month when stored at -20°C. The IC50 values for Pb, Cp, and Pb-Cp were found to be 75, 2.9, and 5 mM, respectively. Pb, Cp, and Pb-Cp inhibited the activity of rat brain AChE in the noncompetitive, mixed, and uncompetitive manners, respectively, with their respective K i values to be 675, 2.37, and 22.72 mM. CONCLUSIONS: The results indicated that the Pb and Cp were able to cause significant alterations in the level and properties of AChE. However, the introduction of lemon juice on Pb- and Cp-treated AChE indicated protection of its activity from their adverse effects. The results may be useful in prospective therapeutic applications of lemon juice or as a food supplement to protect mammalian systems from adverse effects of these toxicants.

Dissipation pattern and safety evaluation of cartap and its metabolites during tea planting, tea manufacturing and brewing.

There are few studies for risk assessment of cartap and its metabolites, although cartap is easily transformed into metabolites which could induce higher toxicity. This study aimed to investigate the dissipation pattern of cartap and its metabolites during tea planting, manufacturing and brewing for evaluating the safety of cartap pesticide. Cartap metabolites were identified using Q-Exactive Orbitrap mass spectrometry. Half-lives of cartap in fresh tea leaves ranged from 0.49 to 0.59 days. Cartap decreased rapidly with time, and it was degraded into nereistoxin and cartap monothiol during tea production chain. Cartap monothiol residues dissipated rapidly by 98% in three days during tea planting. Nereistoxin had a longer residual period than cartap and it dominated the total residue in made tea after tea manufacturing. Transfer rates of nereistoxin during tea brewing ranged from 78.24% to 121.56%. Therefore, we suggested sum of cartap and nereistoxin residues as maximum residual limits in tea.

Simultaneous determination of cartap and its metabolite in tea using hydrophilic interaction chromatography tandem mass spectrometry and the combination of dispersive solid phase extraction and solid phase extraction.

Risk assessment of cartap residue in tea should include the exposure of cartap and its metabolite due to rapid degradation of cartap into nereistoxin. Herein, a reliable method for determination of cartap and nereistoxin in tea was developed by hydrophilic interaction chromatography tandem mass spectrometry. Target compounds were extracted with water containing 1% formic acid and 5 mM ammonium formate. The use of dichloromethane effectively removed caffeine. Tea extracts were cleaned up by dispersive adsorbents of octadecylsilane and strong anion exchanger, then further purified using hydrophilic lipophilic balanced solid phase extraction cartridge. Isotopic internal standard was employed to calibrate the loss of analytes during sample preparation and compensate matrix effects. Method validation illustrated excellent linearity, with correlation coefficients (R2) higher than 0.999. Satisfactory recoveries of target compounds spiked in green tea, black tea and oolong tea ranged from 87.6% to 119.9% with intra- and inter-day precisions below 20%. Limits of quantification of cartap and nereistoxin were 10.0 µg kg-1, and limits of detection were 2.0 µg kg-1 for cartap and 4.0 µg kg-1 for nereistoxin. The developed method was applied to determine cartap and nereistoxin in thirty tea samples.

Biophysical study on the interaction of cartap hydrochloride and hemoglobin: Heme degradation and functional changes of protein.

Cartap hydrochloride is a mildly perilous insecticide known as "Padan" which is used largely in agricultural farms to control weevil and caterpillars. The over use of cartap causes harmful effects on human health. Since the blood may acts as a target and carrier for insecticides, the effect of these compounds on blood in mammalian toxicology is very important. Hemoglobin is a tetramer protein that play critical role in oxygen transport. The aim of this study was to analyze and compare the function and structural changes of hemoglobin in the presence of different concentrations of cartap by employing different spectroscopic techniques. The obtained results show that cartap has a high hemolytic effect which is increased with cartap concentration and reduces the thermal midpoint of hemoglobin. Fluorescence measurements reveal heme degradation at different concentrations of cartap. In consequence of theoretical and experimental results, cartap has an undesirable effect on hemoglobin structure and function.

Rapid Colorimetric Detection of Cartap Residues by AgNP Sensor with Magnetic Molecularly Imprinted Microspheres as Recognition Elements.

The overuse of cartap in tea tree leads to hazardous residues threatening human health. A colorimetric determination was established to detect cartap residues in tea beverages by silver nanoparticles (AgNP) sensor with magnetic molecularly imprinted polymeric microspheres (Fe3O4@mSiO2@MIPs) as recognition elements. Using Fe3O4 as supporting core, mesoporous SiO2 as intermediate shell, methylacrylic acid as functional monomer, and cartap as template, Fe3O4@mSiO2@MIPs were prepared to selectively and magnetically separate cartap from tea solution before colorimetric determination by AgNP sensors. The core-shell Fe3O4@mSiO2@MIPs were also characterized by FT-IR, TEM, VSM, and experimental adsorption. The Fe3O4@mSiO2@MIPs could be rapidly separated by an external magnet in 10 s with good reusability (maintained 95.2% through 10 cycles). The adsorption process of cartap on Fe3O4@mSiO2@MIPs conformed to Langmuir adsorption isotherm with maximum adsorption capacity at 0.257 mmol/g and short equilibrium time of 30 min at 298 K. The AgNP colorimetric method semi-quantified cartap ≥5 mg/L by naked eye and quantified cartap 0.1⁻5 mg/L with LOD 0.01 mg/L by UV-vis spectroscopy. The AgNP colorimetric detection after pretreatment with Fe3O4@mSiO2@MIPs could be successfully utilized to recognize and detect cartap residues in tea beverages.

Advanced analytical method of nereistoxin using mixed-mode cationic exchange solid-phase extraction and GC/MS.

Nereistoxin(NTX) was originated from a marine annelid worm Lumbriconereis heteropoda and its analogue pesticides including cartap, bensultap, thiocyclam and thiobensultap have been commonly used in agriculture, because of their low toxicity and high insecticidal activity. However, NTX has been reported about its inhibitory neuro toxicity in human and animal body, by blocking nicotinic acetylcholine receptor and it cause significant neuromuscular toxicity, resulting in respiratory failure. We developed a new method to determine NTX in biological fluid. The method involves mixed-mode cationic exchange based solid phase extraction and gas chromatography/mass spectrometry for final identification and quantitative analysis. The limit of detection and recovery were substantially better than those of other methods using liquid-liquid extraction or headspace solid phase microextraction. The good recoveries (97±14%) in blood samples were obtained and calibration curves over the range 0.05-20 mg/L have R2 values greater than 0.99. The developed method was applied to a fatal case of cartap intoxication of 74 years old woman who ingested cartap hydrochloride for suicide. Cartap and NTX were detected from postmortem specimens and the cause of the death was ruled to be nereistoxin intoxication. The concentrations of NTX were 2.58 mg/L, 3.36 mg/L and 1479.7 mg/L in heart, femoral blood and stomach liquid content, respectively. The heart blood/femoral blood ratio of NTX was 0.76.

Highly sensitive and selective cartap nanosensor based on luminescence resonance energy transfer between NaYF4:Yb,Ho nanocrystals and gold nanoparticles.

Fluorescent detection is an attractive method for the detection of toxic chemicals. However, most chemosensors that are currently utilized in fluorescent detection are based on organic dyes or quantum dots, which suffer from instability, high background noise and interference from organic impurities in solution, which can also be excited by UV radiation. In the present research, we developed a novel NaYF4:Yb,Ho/Au nanocomposite-based chemosensor with high sensitivity (10 ppb) and selectivity over competing analytes for the detection of the insecticide cartap. This nanosensor is excited with a 970-nm laser instead of UV radiation to give an emission peak at 541 nm. In the presence of cartap, the nanocomposites aggregate, resulting in enhanced luminescence resonance energy transfer between the NaYF4:Yb,Ho nanocrystals and the gold nanoparticles, which decreases the emission intensity at 541 nm. The relative luminescence intensity at 541 nm has a linear relationship with the concentration of cartap in the solution. Based on this behavior, the developed nanosensor successfully detected cartap in farm produce and water samples with satisfactory results.

Cartap hydrochloride poisoning: A clinical experience.

Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [(3)H]-ryanodine binding to the Ca(2+) release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca(2+) influx and induction of internal Ca(2+) release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

Cartap poisoning: A rare case report.

Cartap is a pesticide commonly used to control weevil and caterpillars. It is an analogue of nereistoxin, a neurotoxic substance isolated from the marine annelid Lumbriconereis heteropoda. It causes neuromuscular blockade. Poisoning with cartap is very rare and not yet reported from India. We report a 35-year-old lady with cartap poisoning who presented with nausea, vomiting, and dyspnea. She improved with N-acetyl cysteine and symptomatic management.

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.