Cytogenetic alterations induced by flupyradifurone, a new butenolide insecticide, in human lymphocytes

Flupyradifurone (FPD), a member of the new class of butenolide insecticides, acts on nicotinic acetylcholine receptors. Studies on genotoxic and carcinogenic effects of FPD are very limited. This is the first study to investigate the cytotoxic and genotoxic effects of FPD and its metabolites on human lymphocyte cultures with or without a metabolic activation system (S9 mix) using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 85, 170, and 340 µg/ml of FPD in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. Statistically significant decreases were detected at the medium and highest concentrations for 48 h treatments while decreases in mitotic index (MI) in the presence of the S9 mix were found statistically significant at all FPD concentrations tested when compared with the solvent control. FPD also decreased the nuclear division index (NDI) at the highest concentration (340 µg/ml) in the absence of S9 mix. When compared with the solvent control, increases in CA frequencies were significant at the medium and highest concentrations. Significantly increased MN frequency was only found at the highest FPD concentration in cultures without S9 mix compared with the solvent control while increases in the MN frequencies in the presence of S9 mix were statistically significant at all FPD concentrations. The results of the present study indicate that FPD and its metabolites can show cytotoxic and genotoxic effects in human lymphocytes. More genotoxicity studies are necessary to make a possible risk assessment in humans.

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αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish

Toxins ◽

10.3390/toxins12030197 ◽

2020 ◽

Vol 12 (3) ◽

pp. 197

Author(s):

Matthew J. Rybin ◽

Henrik O’Brien ◽

Iris Bea L. Ramiro ◽

Layla Azam ◽

J. Michael McIntosh ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Neuromuscular Junctions ◽

Functional Characterization ◽

Cone Snail ◽

Nicotinic Acetylcholine ◽

New Class ◽

Goldfish Carassius Auratus ◽

Snake Neurotoxin

We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus. Injections of αM-MIIIJ induced paralysis in goldfish (Carassius auratus) but not mice. Intracellular recording from skeletal muscles of fish (C. auratus) and frog (Xenopus laevis) revealed that αM-MIIIJ inhibited postsynaptic nicotinic acetylcholine receptors (nAChRs) with an IC50 of ~0.1 μM. With comparable potency, αM-MIIIJ reversibly blocked ACh-gated currents (IACh) of voltage-clamped X. laevis oocytes exogenously expressing nAChRs cloned from zebrafish (Danio rerio) muscle. αM-MIIIJ also protected against slowly-reversible block of IACh by α-bungarotoxin (α-BgTX, a snake neurotoxin) and α-conotoxin EI (α-EI, from Conus ermineus another fish hunter) that competitively block nAChRs at the ACh binding site. Furthermore, assessment by fluorescence microscopy showed that αM-MIIIJ inhibited the binding of fluorescently-tagged α-BgTX at neuromuscular junctions of X. laevis, C. auratus, and D. rerio. (Note, we observed that αM-MIIIJ can block adult mouse and human muscle nAChRs exogenously expressed in X. laevis oocytes, but with IC50s ~100-times higher than those of zebrafish nAChRs.) Taken together, these results indicate that αM-MIIIJ inhibits muscle nAChRs and furthermore apparently does so by interfering with the binding of ACh to its receptor. Comparative alignments with homologous sequences identified in other fish hunters revealed that αM-MIIIJ defines a new class of muscle nAChR inhibitors from cone snails.

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Polyarginine Peptides As a New Class of Ligands of Nicotinic Acetylcholine Receptors

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672918060017 ◽

2018 ◽

Vol 483 (1) ◽

pp. 313-315

Author(s):

E. V. Kryukova ◽

I. A. Ivanov ◽

D. S. Lebedev ◽

E. N. Spirova ◽

D. A. Senko ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Nicotinic Acetylcholine ◽

New Class

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Acute poisoning with acetamiprid, a type of neonicotinoid insecticide causing severe lactic acidosis: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x211059296 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110592

Author(s):

Mohanaruban Pravinson ◽

Selladurai Pirasath ◽

Srivickneswaran Ghetheeswaran ◽

Sivahamy Uthayakumaran

Keyword(s):

Lactic Acidosis ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Acute Poisoning ◽

Severe Lactic Acidosis ◽

New Class ◽

The World ◽

Excess Amount ◽

Neonicotinoid Insecticide ◽

Specific Management

Acetamiprid is a type of neonicotinoid that belongs to the new class of insecticides. It is fatally toxic to insects by acting as an agonist to nicotinic acetylcholine receptors. Cases with neonicotinoids including acetamiprid poisoning in humans were reported around the world. Only one case with acetamiprid poisoning associated with severe adverse effects has been described from Sri Lanka. Serious side effects will occur if it is consumed in excess amount. Here, we described a case of acetamiprid poisoning in a man who developed severe lactic acidosis, myocardial suppression, hyperglycemia, and intestinal obstruction following accidental intake of acetamiprid insecticide. The patient was managed conservatively as there is no specific management mentioned in the literature.

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Novel Pathways and Mechanism of Nicotine-Induced Oral Carcinogenesis

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210806161312 ◽

2021 ◽

Vol 16 ◽

Author(s):

Mohit Sharma ◽

Smitha S Shetty ◽

Raghu Radhakrishnan

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Search Strategy ◽

The Novel ◽

Review Of The Literature ◽

Brain Dopamine ◽

Carcinogenic Effect ◽

Oral Carcinogenesis ◽

Carcinogenic Effects ◽

Oral Cancer Cells

Background: Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine-derived Nitrosamines (NDNs). Methods: A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis. Results: Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR. Conclusion: Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.

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Neonicotinoid insecticides: an emerging cause of acute pesticide poisoning

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20192275 ◽

2019 ◽

Vol 6 (3) ◽

pp. 976 ◽

Cited By ~ 1

Author(s):

Pradeep Kumar Bansal ◽

C. L. Nawal ◽

Aradhana Singh ◽

Radheyshyam Chejara ◽

Siddharth Chouhan ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Crop Protection ◽

Kidney Injury ◽

High Specificity ◽

Warning Signs ◽

Selective Toxicity ◽

New Class ◽

Protection Information ◽

Cns Depression

Neonicotinoids are a new class of insecticides widely applied for crop protection. Information on human exposures to neonicotinoids is limited. The most common routes of exposure were ingestion (51%), dermal (44%), and ocular (11%). These insecticides act as agonists at nicotinic acetylcholine receptors, which cause insect paralysis and death the high specificity for receptors in insects was considered to possess highly selective toxicity to insects and relative sparing of mammals. However, an increasing number of cases of acute neonicotinoid poisoning have been reported in recent years. Present study report three cases presented to us with acute neonicotinoid poisoning with different manifestations including acute myocardial infarction, central nervous system (CNS) depression, and acute kidney injury, who recovered subsequently with supportive care. A detailed literature review found that respiratory, cardiovascular and certain neurological presentations are warning signs of severe neonicotinoid intoxication. Supportive treatment and decontamination are the practical methods for the management of all neonicotinoid-poisoned patients.

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An alternative approach to studying the effects of ZnO nanoparticles in cultured human lymphocytes: combining electrochemistry and genotoxicity tests

Archives of Industrial Hygiene and Toxicology ◽

10.1515/aiht-2016-67-2910 ◽

2016 ◽

Vol 67 (4) ◽

pp. 277-288 ◽

Cited By ~ 3

Author(s):

Gina Branica ◽

Marin Mladinić ◽

Dario Omanović ◽

Davor Želježić

Keyword(s):

Human Lymphocytes ◽

High Density ◽

Genotoxic Effects ◽

Zno Nps ◽

Experimental Conditions ◽

Cytogenetic Effects ◽

Alternative Approach ◽

Lymphocyte Cultures ◽

Genotoxicity Tests ◽

Primary Dna Damage

Abstract Nanoparticle use has increased radically raising concern about possible adverse effects in humans. Zinc oxide nanoparticles (ZnO NPs) are among the most common nanomaterials in consumer and medical products. Several studies indicate problems with their safe use. The aim of our study was to see at which levels ZnO NPs start to produce adverse cytogenetic effects in human lymphocytes as an early attempt toward establishing safety limits for ZnO NP exposure in humans. We assessed the genotoxic effects of low ZnO NP concentrations (1.0, 2.5, 5, and 7.5 μg mL-1) in lymphocyte cultures over 14 days of exposure. We also tested whether low and high-density lymphocytes differed in their ability to accumulate ZnO NPs in these experimental conditions. Primary DNA damage (measured with the alkaline comet assay) increased with nanoparticle concentration in unseparated and high density lymphocytes. The same happened with the fragmentation of TP53 (measured with the comet-FISH). Nanoparticle accumulation was significant only with the two highest concentrations, regardless of lymphocyte density. High-density lymphocytes had significantly more intracellular Zn2+ than light-density ones. Our results suggest that exposure to ZnO NPs in concentrations above 5 μg mL-1 increases cytogenetic damage and intracellular Zn2+ levels in lymphocytes.

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IN VITRO GENOTOXICITY OF THREE PLANTS FROM ASTERACEAE FAMILY IN HUMAN LYMPHOCYTES CULTURES

Universal Journal of Pharmaceutical Research ◽

10.22270/ujpr.v6i6.692 ◽

2022 ◽

Author(s):

M. Kinan Aljaja ◽

Adawia Kitaz ◽

Raghda Lahdo

Keyword(s):

Medicinal Plants ◽

Peer Review ◽

Mitotic Index ◽

Human Lymphocyte ◽

Human Lymphocytes ◽

Genotoxic Effects ◽

Medicinal Uses ◽

Lymphocyte Cultures

Background: Onopordum carduiforme, Centaurea verutum, and Achillea santolina are medicinal plants grown in Syria and commonly used in traditional medicine. Such as antibacterial, antioxidant and anticancer properties. However, the genotoxic effects of these plants have not been studied. Aim and objective: the aim of this study was to evaluate the genotoxic effects of hydroethanolic extracts of these plants on human lymphocyte cultures model by evaluating the cell proliferation, determination of mitotic index (MI), and their effects on chromosomes. Methods: the hydroethanolic extracts of the aerial parts of the three plants were extracted using an Ultrasonic bath. Then the genotoxic effects of hydroethanolic extracts of these plants on human lymphocyte cultures was conducting by determination of mitotic index (MI). Results: the results showed that all three plants decreased non-significantly the mean of mitotic index in comparison with negative control (normal MI) (p>0.05) at concentrations (1, 3, 5 mg/ml) and the mitotic index values ranged was between (2.25±0.07 and 3.3±0.28). However, C. verutum showed the lowest mitotic index (3±0.14 at 1 mg/ml) and (2.25±0.07 at 5 mg/ml), and did not induce chromatid or chromosome breaks or gaps. Conclusion: these preliminary results on cytotoxicity and mutagenicity of these plants provide valuable information about the safety of using them in alternative medicine. Peer Review History: Received: 11 November 2021; Revised: 13 December; Accepted: 28 December, Available online: 15 January 2022 Academic Editor: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Ahmad Najib, Universitas Muslim Indonesia, Makassar, Indonesia, [email protected] Dr. Dennis Amaechi, MrsFoluBabade Mini Estate , Flat 5 by Old Soldiers Quarter, Sabongari/Bwari, Abuja- Federal Capital Territory, Nigeria. [email protected] Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, [email protected] Similar Articles: A STUDY ON DIFFERENT PLANTS OF APOCYNACEAE FAMILY AND THEIR MEDICINAL USES STUDY LITERATION OF CHEMICAL CONTENTS OF SOME PLANTS THAT POTENTIALLY AS THE SOLAR SOWS EXPLORING THE ANTIPARASITIC ACTIVITY OF MEDICINAL PLANTS

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Chromosome Aberrations Produced by Mestranol in Human Lymphocyte Cultures

Acta veterinaria ◽

10.2478/acve-2019-0036 ◽

2019 ◽

Vol 69 (4) ◽

pp. 426-433

Author(s):

Radislava Teodorović ◽

Vladimir Drašković ◽

Spomenka Đurić ◽

Kartarina Nenadović ◽

Milorad Mirilović ◽

...

Keyword(s):

Human Lymphocyte ◽

Chromosome Aberrations ◽

Human Lymphocytes ◽

Genotoxic Effects ◽

Robertsonian Translocations ◽

Lymphocyte Cultures ◽

Structural Aberrations ◽

Numerical Aberrations ◽

Dose Dependent

Abstract In this investigation, the genotoxic properties of mestranol were examined in vitro. Human lymphocyte cultures were exposed for 72 h to mestranol at concentrations of 7.5, 15 and 30 µg/g. The genotoxic effects of the chemosterilant were assessed by numerical and structural chromosome aberrations. Mestranol induced certain genotoxic effects in human lymphocytes. There was a dose-dependent significant (p<0.01) increase in the number of numerical aberrations in comparison to the control, but without significant differences (p>0.05) between the doses applied. Further, structural aberrations increased significantly (p<0.01) in the presence of mestranol, being most frequent in cultures exposed to the highest mestranol dose. The frequency of Robertsonian translocations increased significantly only in cultures treated with mestranol at concentration of 30 µg/g in comparison both with the control (p<0.01) and the lowest chemosterilant dose (p<0.01). There were significant differences (p<0.01) in the levels of chromosome gaps and fragments compared to Robertsonian translocations, whilst the frequencies between gaps and fragments were not significantly different (p>0.05).

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