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Jinjun Wang - One of the best experts on this subject based on the ideXlab platform.
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A glutathione S‐transferase (BdGSTd9) participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in Bactrocera dorsalis (Hendel)
Pest management science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Li‐sha Zheng, Wen-jie Bai, Guy Smagghe, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
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a glutathione s transferase bdgstd9 participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in bactrocera dorsalis hendel
Pest Management Science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Wen-jie Bai, Guy Smagghe, Lisha Zheng, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
Marcelo Farina - One of the best experts on this subject based on the ideXlab platform.
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in vitro reactivating effects of standard and newly developed oximes on Malaoxon inhibited mouse brain acetylcholinesterase
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Alessandra Antunes Dos Santos, Alcir Luiz Dafre, Diogo O. Souza, João Rocha, Kamil Kuca, Danubia Bonfanti Santos, Andreza Fabro De Bem, Marcelo FarinaAbstract:Abstract: Malathion is an organophosphate (OP) pesticide whose toxicity depends on its bioactivation to Malaoxon. Human malathion poisoning has been treated with oximes (mainly pralidoxime) in an attempt to reactivate OP-inhibited acetylcholinesterase (AChE). However, pralidoxime has shown unsatisfactory therapeutic effects in malathion poisoning and its routine use has been questioned. In this study, we evaluated the in vitro potency of standards and newly developed oximes in reactivating Malaoxon-inhibited AChE derived from mouse brain supernatants. Malaoxon displayed a concentration-dependent inhibitory effect on mouse brain AChE (IC50 = 2.36 μM), and pralidoxime caused a modest reactivating effect (30% of reactivation at 600 μM). Obidoxime and trimedoxime, as well as K047 and K075, displayed higher reactivating effects (from 55% to 70% of reactivation at 600 μM) when compared with pralidoxime. The results show that obidoxime, trimedoxime, K074 and K075 present higher reactivating effects on Malaoxon-inhibited AChE under in vitro conditions when compared with pralidoxime. Taking into account the unsatisfactory effects of pralidoxime as antidotal treatment in malathion poisonings, the present results suggest that obidoxime, trimedoxime, K074 and K075 might be interesting therapeutic strategies to reactivate Malaoxon-inhibited AChE in malathion poisonings.
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In vitro Reactivating Effects of Standard and Newly Developed Oximes on Malaoxon‐Inhibited Mouse Brain Acetylcholinesterase
Basic & clinical pharmacology & toxicology, 2010Co-Authors: Alessandra Antunes Dos Santos, Danúbia Bonfanti Dos Santos, Alcir Luiz Dafre, Diogo O. Souza, João Rocha, Kamil Kuca, Marcelo FarinaAbstract:Abstract: Malathion is an organophosphate (OP) pesticide whose toxicity depends on its bioactivation to Malaoxon. Human malathion poisoning has been treated with oximes (mainly pralidoxime) in an attempt to reactivate OP-inhibited acetylcholinesterase (AChE). However, pralidoxime has shown unsatisfactory therapeutic effects in malathion poisoning and its routine use has been questioned. In this study, we evaluated the in vitro potency of standards and newly developed oximes in reactivating Malaoxon-inhibited AChE derived from mouse brain supernatants. Malaoxon displayed a concentration-dependent inhibitory effect on mouse brain AChE (IC50 = 2.36 μM), and pralidoxime caused a modest reactivating effect (30% of reactivation at 600 μM). Obidoxime and trimedoxime, as well as K047 and K075, displayed higher reactivating effects (from 55% to 70% of reactivation at 600 μM) when compared with pralidoxime. The results show that obidoxime, trimedoxime, K074 and K075 present higher reactivating effects on Malaoxon-inhibited AChE under in vitro conditions when compared with pralidoxime. Taking into account the unsatisfactory effects of pralidoxime as antidotal treatment in malathion poisonings, the present results suggest that obidoxime, trimedoxime, K074 and K075 might be interesting therapeutic strategies to reactivate Malaoxon-inhibited AChE in malathion poisonings.
Guy Smagghe - One of the best experts on this subject based on the ideXlab platform.
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A glutathione S‐transferase (BdGSTd9) participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in Bactrocera dorsalis (Hendel)
Pest management science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Li‐sha Zheng, Wen-jie Bai, Guy Smagghe, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
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a glutathione s transferase bdgstd9 participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in bactrocera dorsalis hendel
Pest Management Science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Wen-jie Bai, Guy Smagghe, Lisha Zheng, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
Li-wei Meng - One of the best experts on this subject based on the ideXlab platform.
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A glutathione S‐transferase (BdGSTd9) participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in Bactrocera dorsalis (Hendel)
Pest management science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Li‐sha Zheng, Wen-jie Bai, Guy Smagghe, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
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a glutathione s transferase bdgstd9 participates in malathion resistance via directly depleting malathion and its toxic oxide Malaoxon in bactrocera dorsalis hendel
Pest Management Science, 2020Co-Authors: Li-wei Meng, Meng-lan Peng, Meng-ling Chen, Guo-rui Yuan, Wen-jie Bai, Guy Smagghe, Lisha Zheng, Jinjun WangAbstract:Background The oriental fruit fly, Bactrocera dorsalis (Hendel), is a widespread agricultural pest that has evolved resistance to many commonly used insecticides including malathion. Glutathione S-transferases (GSTs) are multifunctional enzymes that metabolize insecticides directly or indirectly. The specific mechanism used by GSTs to confer malathion resistance in B. dorsalis is unclear. Results BdGSTd9 was identified from B. dorsalis and was expressed at twice the level in a malathion-resistant strain (MR) than in a susceptible strain (MS). By using RNAi of BdGSTd9, the toxicity of malathion against MR was increased. Protein modelling and docking of BdGSTd9 with malathion and Malaoxon indicated key amino acid residues for direct binding in the active site. In vitro assays with engineered Sf9 cells overexpressing BdGSTd9 demonstrated lower cytotoxicity of malathion. High performance liquid chromatography (HPLC) analysis indicated that malathion could be broken down significantly by BdGSTd9, and it also could deplete the malathion metabolite Malaoxon, which possesses a higher toxicity to B. dorsalis. Taken together, the BdGSTd9 of B. dorsalis could not only deplete malathion, but also react with Malaoxon and therefore enhance malathion resistance. Conclusion BdGSTd9 is a component of malathion resistance in B. dorsalis. It acts by depleting both malathion and Malaoxon. © 2020 Society of Chemical Industry.
Janusz Blasiak - One of the best experts on this subject based on the ideXlab platform.
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Genotoxicity of Malaoxon: Induction of Oxidized and Methylated Bases and Protective Effect of α-Tocopherol
Pesticide Biochemistry and Physiology, 2001Co-Authors: Janusz Blasiak, Dorota L. StankowskaAbstract:Abstract Malaoxon, the first and main metabolite of malathion, unlike its parent compound, can damage DNA in human lymphocytes, by mechanism(s) including oxidative action. Vitamin C may inhibit the DNA-damaging effect of Malaoxon. To explore this effect further, we investigated the action of Malaoxon on DNA in lymphocytes pretreated with a potent antioxidant, α-tocopherol (vitamin E), using the single-cell gel electrophoresis (comet assay). Addition of α-tocopherol to a final concentration of 20 and 80 μM reduced a dose-dependent DNA damaging effect of a 1-h incubation of human peripheral blood lymphocytes at 37°C with Malaoxon at 25, 75, or 200 μM, measured as the increase in the comet tail moment of the lymphocytes. Lymphocytes treated with α-tocopherol displayed faster kinetics of removing damage to their DNA, and α-tocopherol abolished the cytotoxic effect of Malaoxon at 200 μM. The protective action of α-tocopherol followed from its interaction with DNA or with Malaoxon bound to DNA or lymphocytes rather than from chemical inactivation of Malaoxon by it. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by Malaoxon. Lymphocytes exposed to Malaoxon and treated with formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, enzymes recognizing oxidized and methylated bases, displayed a greater extent of DNA damage than those not treated with these enzymes. The results suggest that hydrogen peroxide and reactive oxygen species may be involved in the formation of DNA lesions induced by Malaoxon. Malaoxon can also methylate DNA bases, and α-tocopherol can be considered a protective agent against DNA damage in persons occupationally exposed to malathion/Malaoxon.
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Protective Action of Sodium Ascorbate against the DNA-Damaging Effect of Malaoxon
Pesticide Biochemistry and Physiology, 1999Co-Authors: Janusz Blasiak, Joanna KowalikAbstract:Abstract In our previous work we showed that Malaoxon, the first and main metabolite of the commonly used organophosphorus insecticide malathion, unlike its parent compound, damaged DNA in human lymphocytes. To search for the mechanism(s) underlying the observed effect we investigated the action of Malaoxon on DNA in lymphocytes pretreated with sodium ascorbate using the single-cell gel electrophoresis (comet assay). On 1-h incubation at 37°C, sodium ascorbate at a concentration of 10 μM reduced a dose-dependent DNA damaging effect of 1-h incubation of human peripheral blood lymphocytes at 37°C with Malaoxon at 25, 75, or 200 μM, measured as the increase in the comet tail moment of the lymphocytes. Treated cells were able to recover within a 30-min incubation in Malaoxon-free medium at 37°C, except for the lymphocytes exposed to the chemical at 200 μM, which did not show measurable DNA repair even on a 120-min incubation. The latter result suggests a considerable cytotoxic effect (cell death) of Malaoxon at the highest concentration used. Sodium ascorbate at 10 μM abolished this cytotoxic effect of Malaoxon. Sodium ascorbate displayed an antioxidant potency in the concentrations up to 50 μM, reducing DNA damage evoked by hydrogen peroxide. We showed that the ascorbate partly inactivated Malaoxon and this inactivation may be, at least in part, responsible for the observed protective effect of the ascorbate. Lymphocytes treated with endonuclease III, which recognizes oxidized pyrimidines, displayed greater tail moment than those untreated with the enzyme, suggesting that the damages induced by Malaoxon have, at least in part, an oxidative origin. In conclusions, sodium ascorbate exerted the protective effect against DNA damage induced by Malaoxon by direct inactivation of it and probably by a mechanism which may involve antioxidative action.
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In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues.
Mutation research, 1999Co-Authors: Janusz Blasiak, Paweł Jałoszyński, A. Trzeciak, Krzysztof SzyfterAbstract:Malathion [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorodithioate] is a commonly used organophosphorus insecticide reported to be genotoxic both in vivo and in vitro, but the reports are conflicting. In order to elucidate the genotoxic potency of the main compounds present in commercial preparations of malathion, the DNA-damaging effect of this insecticide, its major metabolite Malaoxon [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorothiolate] and its isomer isomalathion [S-(1,2-dicarboethoxyethyl)O,S-dimethyl phosphorodithioate], all at purity of at least 99.8%, was investigated by use of the alkaline single cell gel electrophoresis (comet assay). Freshly isolated human peripheral blood lymphocytes were incubated with 25, 75 and 200 μM of the chemicals for 1 h at 37°C. The concentrations used are comparable to those found in blood following various non-lethal human exposures to pesticides. Malathion did not cause any significant changes in the comet length of the lymphocytes, throughout the range of concentrations tested. Malaoxon and isomalathion introduced damage to DNA in a dose-dependent manner. The effect induced by Malaoxon was more pronounced than that caused by isomalathion. Treated cells were able to recover within a 60-min incubation in insecticide-free medium at 37°C except the lymphocytes exposed to Malaoxon at 200 μM, which did not show measurable DNA repair. The latter result suggests a considerable cytotoxic effect (cell death) of Malaoxon at the highest concentration used. The reported genotoxicity of malathion might, therefore, be a consequence of its metabolic biotransformation to Malaoxon or the presence of Malaoxon and/or isomalathion as well as other unspecified impurities in commercial formulations of malathion. In this regard, the results of our study clearly indicate that malathion used as commercial product, i.e., containing Malaoxon and isomalathion, can be considered as a genotoxic substance in vitro. This means that it may also produce DNA disturbances in vivo, such as DNA breakage at sites of oncogenes or tumor suppressor genes, thus playing a role in the induction of malignancies in individuals exposed to this agent. Therefore, malathion can be regarded as a potential mutagen/carcinogen and requires further investigation.
