Stomach absorption of intubated insecticides in fasted mice

Ahdaya, S.M.; Guthrie, F. E.

doi:10.1016/0300-483x(81)90025-1

Cited by 14 publications

(5 citation statements)

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“…Carbofuran is a very toxic carbamate compound and among the most readily absorbed insecticides as compared to several well-known pesticides including carbaryl, chlorpyrifos, dichlorodiphenyltrichloroethane (DDT), malathion, and parathion. Upon rapid absorption through the skin, lungs, GI tract, and mucous membranes, carbofuran is distributed to all organs and is rapidly eliminated. ,, Over the years, carbofuran poisoning has been extensively studied by many researchers in humans, insects, mice, and plants. − In humans, carbofuran metabolism is mediated by the cytochrome P450 (CYP3A4) enzyme, which is one of the most abundant drug-metabolizing CYP isoforms in the human liver that metabolizes endogenous compounds. The main pathway of oxidative metabolism of carbofuran in animals, insects, and plants appears to consist of hydroxylation of a benzylic carbon to yield a major ring oxidation metabolite, 3-hydroxycarbofuran, and two minor metabolites (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…Upon rapid absorption through the skin, lungs, GI tract, and mucous membranes, carbofuran is distributed to all organs and is rapidly eliminated. 3,37,38 Over the years, carbofuran poisoning has been extensively studied by many researchers in humans, insects, mice, and plants. 39−42 In humans, carbofuran metabolism is mediated by the cytochrome P450 (CYP3A4) enzyme, which is one of the most abundant drug-metabolizing CYP isoforms in the human liver that metabolizes endogenous compounds.…”

Section: ■ Resultsmentioning

confidence: 99%

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Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan

Rehman

Khan

Shad

et al. 2016

Chem. Res. Toxicol.

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This study was conducted to investigate the protein adducts with pesticides in a cohort of 172 factory workers that were exposed to a mixture of pesticides. The 35 samples showing considerable variation in biochemical parameters, i.e., butyrylcholinestrase (BChE), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transferase (GGT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP/ALKP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK) enzymes, and controls were analyzed by reversed-phase nanoscale liquid chromatography tandem mass spectrometry (nLC-MS/MS) on an Orbitrap mass spectrometer employing a shotgun proteomics approach. Only protein adducts with carbofuran were found on serum proteins of these workers. These adducts were of carbofuran labeled lysine (Lys-142, Lys-183, Lys-287, and Lys-467), arginine (Arg-210, Arg-242, and Arg-256) from serum albumin, and serine (Ser-07, Ser-54, and Ser-150) from immunoglobulin proteins. The arginine residues (Arg-210, Arg-242, Arg-246, and Arg-434) from albumin were also found to be glycated in serum of workers showing a high level of glucose who also had glycated arginine (Arg-1120) modified with carbofuran in their tankyrase-1-binding protein. The number of tandem mass spectra of modified peptides increased with increasing time of exposure. This is the first report to demonstrate the presence of carbofuran-labeled albumin, immunoglobulin, and glycated arginine, which shows that lysine and arginine of human albumin and serine of immunoglobulin are covalently modified in the serum of workers that were occupationally exposed to carbofuran, and the modification is detectable by tandem mass spectrometry. These peptides modified with carbofuran can potentially be used as a biomarker of carbofuran exposure.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Resultsmentioning

confidence: 99%

Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan

Rehman

Khan

Shad

et al. 2016

Chem. Res. Toxicol.

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“…CPS administered in corn oil appears to be well absorbed (around 80%) over a range of dose levels and the HFD animals receive a larger amount of CPS when compared to STD animals due to the increased body weights of HFD animals. [ 17,37 ] Exposure to CPS (10 mg/kg) in TK‐NOG mice decreased plasma BChE activity by approximately one half compared to control mice with peak inhibition observed after 0.5 h and exposure to CPS (30 mg/kg) produced peak plasma levels of CPS after 2–4 h. Detectable CPS levels were found up to 7 h after dosing. [ 21,38 ] The current dosage in this study is considered a high dose and utilized to quantitatively measure the CPS and TCP levels.…”

Section: Discussionmentioning

confidence: 99%

Effect of high fat diet on the toxicokinetics and toxicodynamics of chlorpyrifos following acute exposure in male C57BL/6J mice

Kondakala

Ross

Chambers

et al. 2022

J Biochem & Molecular Tox

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Chlorpyrifos (CPS) is one of the most widely used organophosphate (OP) insecticides. The acute neurotoxicity of OPs results from the inhibition of acetylcholinesterase (AChE). However, some OPs also inhibit noncholinergic targets including monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and carboxylesterase (CES). Data have shown that highly lipophilic OPs, including CPS, have a persistent toxic effect in obese patients. Therefore, the present study was designed to determine the effect of high fat diet (HFD) induced obesity on the disposition of CPS and its detoxified metabolite 3,5,6-trichloro-2-pyridinol (TCP) following acute exposure as well as effects on cholinergic and noncholinergic CPS targets. Male C57BL/6J mice were fed a standard diet (STD) or HFD for 4 weeks, then treated with vehicle or CPS (25 mg/kg) via oral gavage and euthanized postdosing at 0, 3, 6, and 12 h. Following exposure, CPS levels in adipose tissue of HFD fed animals were increased to a greater extent than in STD fed animals, whereas overall hepatic TCP levels were decreased in HFD fed animals. Red blood cell (RBC) AChE and plasma cholinesterase activities were inhibited regardless of diet intake, but inhibition of RBC AChE activity was significantly lower after 3 h in HFD animals. Hepatic CES and FAAH activities were also significantly decreased following CPS exposure regardless of diet. In conclusion, increased time-integrated CPS levels in adipose tissue indicate CPS may possibly form a depot there and may be retained longer in obese animals than in normal animals.acetylcholinesterase, carboxylesterase, chlorpyrifos, endocannabinoid system, high fat diet | INTRODUCTIONOrganophosphates (OPs) have been widely used as pesticides in agriculture and household settings. Chlorpyrifos (CPS) is one of the most widely used phosphorothioate insecticides in agriculture settings where it is used mainly on corn, cotton, soy beans, in addition to other crops. [1] CPS is bioactivated via a desulfuration reaction catalyzed by cytochrome P450s (CYP450) to form chlorpyrifos oxon (CPO), which is a potent inhibitor of acetylcholinesterase (AChE). [2] The CYP450 isozymes also mediate the detoxication of CPS to form 3,5,6-trichloro-2-pyridinol (TCP). [3,4] In addition to CYP450 mediated detoxication, CPO can also be detoxified to TCP via hydrolysis by paraoxonase-1 (PON-1) and carboxylesterases (CES). [5,6] Along with the primary cholinergic toxicity produced by inhibition of AChE in the

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“…Previous studies have revealed that acute oral exposure to CPS (1 or 2.0 mg/kg) do not significantly alter RBC AChE activities in humans which is in contrast to our previous studies demonstrating marked inhibition of RBC AChE activity following oral exposure to CPS (2.0 mg/kg) by 39% in C57BL/6J mice (Griffin et al, 1999; Kondakala et al, 2017; Timchalk et al, 2002). This difference may be due to differences in oral absorption of CPS between species with approximately 70% absorption in humans and 90% absorption in mice (Ahdaya and Guthrie, 1981; Nolan et al, 1984). With regards to repeated exposures of CPS as used in the current study, a NOAEL of 0.1 mg/kg/day for humans in terms of RBC AChE inhibition has been reported which is greater than ten-fold lower than the presently utilized concentration of CPS (Coulston et al, 1972).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cholinergic and non-cholinergic targets following subacute exposure to chlorpyrifos in normal and high fat fed male C57BL/6J mice

Howell

Kondakala

Holdridge

et al. 2018

Food and Chemical Toxicology

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The effects of obesity on organophosphate pesticide-mediated toxicities, including both cholinergic and non-cholinergic targets, have not been fully elucidated. Therefore, the present study was designed to determine if high fat diet intake alters the effects of repeated exposure to chlorpyrifos (CPS) on the activities of both cholinergic and noncholinergic serine hydrolase targets. Male C57BL/6J mice were placed on either standard rodent chow or high fat diet for four weeks with CPS exposure (2.0 mg/kg) for the last 10 days of diet intake. Exposure to CPS did not alter acetylcholinesterase in the central nervous system, but it did significantly inhibit circulating cholinesterase activities in both diet groups. CPS significantly inhibited hepatic carboxylesterase and fatty acid amide hydrolase and this inhibition was significantly greater in high fat fed animals. Additionally, CPS exposure and high fat diet intake downregulated genes involved in hepatic de novo lipogenesis as well as cytochrome P450 enzymes involved in hepatic xenobiotic metabolism. In summary, the present study demonstrates that high fat diet intake potentiates CPS mediated inhibition of both carboxylesterase and fatty acid amide hydrolase in the liver of obese animals following subacute exposure and suggests obesity may be a risk factor for increased non-cholinergic hepatic CPS toxicity.

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Stomach absorption of intubated insecticides in fasted mice

Cited by 14 publications

References 6 publications

Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan

Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan

Effect of high fat diet on the toxicokinetics and toxicodynamics of chlorpyrifos following acute exposure in male C57BL/6J mice

Inhibition of cholinergic and non-cholinergic targets following subacute exposure to chlorpyrifos in normal and high fat fed male C57BL/6J mice

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