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Mechanisms of piperonyl butoxide cytotoxicity and its enhancement with imidacloprid and metals in Chinese hamster ovary cells. Mutation research The widespread use of chemicals and the presence of chemical and metal residues in various foods, beverages, and other consumables have raised concerns about the potential for enhanced toxicity. This study assessed the cytotoxic effects of Piperonyl butoxide (PBO) and its enhancement by combination with major contamination chemicals including Imidacloprid and metals, using different cytotoxic and genotoxic assays in Chinese hamster ovary (CHO) cells. PBO exhibited elevated cytotoxic effects in poly (ADP-ribose) polymerase (PARP) deficient CHO mutants but not in Glutathione S-transferase deficient CHO mutants. PBO cytotoxicity was enhanced by PARP inhibitor, Olaparib. PBO cytotoxicity was also enhanced with co-exposure to Imidacloprid, Lead Chloride, or Sodium Selenite. PBO induces γH2AX foci formation and apoptosis. The induction of DNA damage markers was elevated with PARP deficiency and co-exposure to Imidacloprid, Lead Chloride, or Sodium Selenite. Moreover, PBO triggers to form etch pits on plastic surfaces. These results revealed novel mechanisms of PBO cytotoxicity associated with PARP and synergistic effects with other environmental pollutants. The toxicological mechanisms underlying exposure to various combinations at different concentrations, including concentrations below the permitted limit of intake or the level of concern, require further study. 10.1016/j.mrfmmm.2024.111853
DNA damage and oxidative stress induced by imidacloprid exposure in the earthworm Eisenia fetida. Wang Juan,Wang Jinhua,Wang Guangchi,Zhu Lusheng,Wang Jun Chemosphere To investigate the soil ecological effect of imidacloprid, earthworm Eisenia fetida was exposed to various concentrations of imidacloprid (0.10, 0.50, and 1.00 mg kg(-1) soil) respectively after 7, 14, 21, and 28 d. The effect of imidacloprid on reactive oxygen species (ROS) generation, antioxidant enzymes activity [superoxide dismutase (SOD) and catalase (CAT), glutathione S-transferase enzyme (GST)], malondialdehyde (MDA) content and DNA damage of the E. fetida was investigated. Significant increase of the ROS level was observed. The SOD and GST activity were significantly induced at most exposure intervals. CAT activity was inhibited and reflected a dose-dependent relationship on days 7, 14 and 21. High MDA levels were observed and the olive tail moment (OTM) as well as the percentage of DNA in the comet tail (tail DNA%) in comet assay declined with increasing concentrations and exposure time after 7 d. Our results suggested that the sub-chronic exposure of imidacloprid caused DNA damage and lipid peroxidation (LPO) leading to antioxidant responses in earthworm E. fetida. 10.1016/j.chemosphere.2015.09.004
A 90 days oral toxicity of imidacloprid in female rats: morphological, biochemical and histopathological evaluations. Bhardwaj Shipra,Srivastava M K,Kapoor Upasana,Srivastava L P Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association A 90 days oral toxicity study of imidacloprid was conducted in female rats with doses of 0, 5, 10, 20mg/kg/day. Decrease in the body weight gain was observed at 20mg/kg/day and at necropsy the relative body weights of liver, kidney and adrenal was also significantly increased at this dose level. No mortality occurred during treatment period while food intake was reduced at high dose level. In clinical chemistry parameters high dose of imidacloprid has caused significant elevation of serum GOT, GPT, glucose and BUN and decreased the activity of AChE in serum and brain. The spontaneous locomotor activity was also decreased at highest dose exposure where as there were no significant changes in hematological and urine parameters. The brain, liver and kidney of rats exposed with high dose of imidacloprid had showed mild pathological changes. Based on the morphological, biochemical, hematological and neuropathological studies it is evident that imidacloprid has not produced any significant effects at 5 and 10mg/kg/day doses but induced toxicological effects at 20mg/kg/day to female rats. Hence, 10mg/kg/day dose may be considered as no observed effect level (NOEL) for female rats. 10.1016/j.fct.2010.02.009
A detailed study of developmental immunotoxicity of imidacloprid in Wistar rats. Gawade Lalita,Dadarkar Shruta S,Husain Raghib,Gatne Madhumanjiri Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Human exposure to imidacloprid is likely to occur during its use as an acaricide or an ectoparasiticide. Accordingly, the developmental immunotoxic potential of imidacloprid was investigated. Oral exposure was initiated in timed pregnant female Wistar rats on gestation day 6 (GD 6) till GD 21. On GD 20, half of the gravid dams were sacrificed, and in utero fetal development was assessed. In the other half of the dams, administration was continued till weaning on postnatal day 21 (PND 21) and maternal toxicity was investigated. A subgroup of weaned pups was sacrificed to assess immunotoxicity parameters. The other half of the pups were exposed to imidacloprid till PND 42, and immunotoxicity was assessed. The findings revealed post-implantation loss in the highest dose group, indicating the risk of abortion. Soft tissue abnormalities and skeletal alterations were observed in the highest dose group. Humoral immunity was assessed by estimating hemagglutination titer and immunoglobulin production. Cell mediated immunity was assessed by Delayed Type Hypersensitivity, whereas, non-specific immunity was assessed by phagocytic index, and other phenotypic parameters. These data revealed that imidacloprid caused age-dependent adverse effects on the developing immunity which was aggravated when exposure continued throughout development, leading to a compromised immune system. 10.1016/j.fct.2012.09.009
Immunotoxic effects of imidacloprid following 28 days of oral exposure in BALB/c mice. Badgujar Prarabdh C,Jain S K,Singh Ajit,Punia J S,Gupta R P,Chandratre Gauri A Environmental toxicology and pharmacology Imidacloprid, a neonicotinoid insecticide has been in use worldwide for several years in agriculture and veterinary medicine. It is possible that residue of this compound may be recycled in the food chain and thus information regarding effects from potential exposure to it is warranted. The objective of the present study was to evaluate immunotoxic effects of imidacloprid in female BALB/c mice. Imidacloprid was administered orally daily at 10, 5, or 2.5mg/kg over 28 days. Specific parameters of humoral and cellular immune response including hemagglutinating antibody (HA) titer to sheep red blood cells (SRBC; T-dependent antigen), delayed type hypersensitivity (DTH) response to SRBC, and T-lymphocyte proliferation in response to phytohemagglutinin (PHA) were evaluated. The results showed that imidacloprid at high dose, specifically suppressed cell-mediated immune response as was evident from decreased DTH response and decreased stimulation index of T-lymphocytes to PHA. At this dose, there were also prominent histopathological alterations in spleen and liver. Histopathological analysis of footpad sections of mice revealed dose-related suppression of DTH response. Imidacloprid at low dose of 2.5mg/kg/day did not produce any significant alterations in cellular and humoral immune response and it seemed to be an appropriate dose for assessment of 'no observable adverse effects level' for immunotoxicity in BALB/c mice. The results also indicated that imidacloprid has immunosuppressive effects at doses >5mg/kg, which could potentially be attributed to direct cytotoxic effects of IMD against T cells (particularly TH cells) and that long-term exposure could be detrimental to the immune system. 10.1016/j.etap.2013.01.012
The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid. El-Gendy Kawther S,Aly Nagat M,Mahmoud Fatma H,Kenawy Anter,El-Sebae Abdel Khalek H Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD(50)) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-s-transferase (GST). Also, the protective effect of vitamin C (200mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD(50)) of imidacloprid after 24h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment. 10.1016/j.fct.2009.10.003
Insecticide imidacloprid induces morphological and DNA damage through oxidative toxicity on the reproductive organs of developing male rats. Bal Ramazan,Naziroğlu Mustafa,Türk Gaffari,Yilmaz Ökkes,Kuloğlu Tuncay,Etem Ebru,Baydas Giyasettin Cell biochemistry and function We investigated whether treatment with imidacloprid would induce morphological changes, DNA fragmentation, antioxidant imbalance and apoptosis in the reproductive system of developing male rats. Twenty-four male rats were included in this 90-day study, starting at 7 days of age. The rats were divided into four groups. The first group was used as control. The second, third and fourth groups received oral 0.5-, 2- and 8-mg/kg imidacloprid, respectively. Serum, sperm and testis samples were collected from all groups at the end of the experimental period. The weights of the epididymis, vesicula seminalis, epididymal sperm concentration, body weight gain, testosterone and reduced glutathione values were lower in the imidacloprid-treated groups than that in the controls. All treated groups had increased lipid peroxidation, fatty acid concentrations and higher rates of abnormal sperm. Apoptosis and fragmentation of seminal DNA were higher in rats treated at the two higher doses of imidacloprid. These results show that this compound has a negative effect on sperm and testis of rats. 10.1002/cbf.2826
Effect of imidacloprid on antioxidant enzymes and lipid peroxidation in female rats to derive its No Observed Effect Level (NOEL). Kapoor Upasana,Srivastava Mithilesh Kumar,Bhardwaj Shipra,Srivastava Laxman Prasad The Journal of toxicological sciences Technical imidacloprid was evaluated for its effect on oxidative stress and Lipid peroxidation (LPO) in female rats for No Observed Effect Level (NOEL). Activities of Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and level of Glutathione (GSH) and LPO were estimated in liver, kidney and brain of rats after oral administration of imidacloprid (5, 10, 20 mg/kg/day) for 90 days. Imidacloprid at 5 and 10 mg/kg/day has not produced changes in SOD, CAT, GPx and level of GSH and LPO in liver, brain and kidney. However 20 mg/kg/day has produced significant changes in SOD, CAT, GPx, GSH, LPO in liver; SOD, CAT and GPx in brain and LPO in kidney. Therefore, it is concluded that imidacloprid has not generated oxidative stress at 5 and 10mg/kg/day but induced changes at 20 mg/kg/day. Hence 10 mg/kg/day may be considered as NOEL through antioxidant enzymes and LPO in female rats.
Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio rerio). Ge Weili,Yan Saihong,Wang Jinhua,Zhu Lusheng,Chen Aimei,Wang Jun Journal of agricultural and food chemistry Imidacloprid is a neonicotinoid insecticide that can have negative effects on nontarget animals. The present study was conducted to assess the toxicity of various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7, 14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST), and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably increased during early exposure but were inhibited toward the end of the exposure period. In addition, the CAT levels decreased to the control level following their elevation during early exposure. High concentrations of imidacloprid (1.25 and 5 mg/L) induced excessive ROS production and markedly increased MDA content on the 21st day of exposure. DNA damage was dose- and time-dependent. In conclusion, the present study showed that imidacloprid can induce oxidative stress and DNA damage in zebrafish. 10.1021/jf504895h
Lack of genotoxic potential of pesticides, spinosad, imidacloprid and neem oil in mice (Mus musculus). Saxena Ankita,Kesari V P Journal of environmental biology Pesticides, spinosad, imidacloprid and neem oil are widely used both in residential and agricultural environments because of its broad spectrum insecticidal activity and effectiveness. The present study was undertaken to estimate genotoxicity of formulations of some pesticides in mice. Three pesticides of diverse group studied were spinosad (45% w/v), imidacloprid (17.8%, w/v) and neem oil. Animals were exposed 37, 4.5 and 50 mg kg⁻¹ b.wt. for spinosad, imidacloprid and neem oil, respectively, through oral gavage for 5 consecutive days. A vehicle control group and one positive control (cyclophosphamide; 20 mg kg⁻¹ b. wt.) were also selected. The results showed that cyclophosphamide produced 1.12% micronuclei in mice, as against 0.18 in vehicle control, 0.30 in spinosad, 0.28 in imidacloprid and 0.22% in neem oil, respectively. The gross percentage of chromosomal aberration in mice were 28.5% in cyclophosphamide against 6.5% in vehicle control, 8.0% in spinosad, 9.5% in imidacloprid and 7.0% in neem oil, respectively. The overall findings of the present study revealed that all the three pesticide formulations, imidacloprid, spinosad and neem oil at tested dose did not show any genotoxic effect in mice.
Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials. Yardimci Mustafa,Sevgiler Yusuf,Rencuzogullari Eyyup,Arslan Mehmet,Buyukleyla Mehmet,Yilmaz Mehmet Arhiv za higijenu rada i toksikologiju Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid's adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg⁻¹) or in combination with piperonyl butoxide (100 mg kg⁻¹) or menadione (25 mg kg⁻¹) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity. 10.2478/10004-1254-65-2014-2554
Low Concentration of Quercetin Reduces the Lethal and Sublethal Effects of Imidacloprid on Apis cerana (Hymenoptera: Apidae). Liu Jialin,Li Yaying,Zhang Zihui,Luo Wenhua,Cao Lan,Liu Huai Journal of economic entomology Large-scale use of systemic pesticides has been considered a potential factor for pollinator population decline. Phytochemicals, e.g., quercetin, have been demonstrated to increase the pesticide tolerance of Apis mellifera Linnaeus (Hymenoptera: Apidae), which is helpful to develop strategies to reduce the pesticides hazards to pollinators. In this study, we hypothesized phytochemicals could reduce the detrimental effects of imidacloprid on Apis cerana Fabricius. The lethal and sublethal effects of imidacloprid on A. cerana workers were investigated. The results showed that A. cerana workers chronically exposed to 100 μg/liter imidacloprid had a significantly shorter longevity by 10.81 d compared with control. Acute exposure to imidacloprid at 100 μg/liter impaired the sucrose responsiveness and memory retention of the workers, and 20 μg/liter reduced the sucrose responsiveness. The treatment with 37.8 mg/liter quercetin for 24 h could increase the longevity of A. cerana workers when chronically exposed to 100 μg/liter imidacloprid, and 75.6 mg/liter quercetin feeding treatment alleviated the impairment of sucrose responsiveness. However, workers treated with 151.2 mg/liter and 75.6 mg/liter quercetin had a significantly shorter longevity compared to that of bees chronically exposed to 100 μg/liter imidacloprid without quercetin treatment. Our results suggested that quercetin treatment could produce a biphasic influence on the lethal effects of imidacloprid on A. cerana. Quercetin at 37.8 mg/liter and 75.6 mg/liter in the diet before pesticide exposure was able to reduce the lethal and sublethal effects of imidacloprid, respectively, providing potential strategies to reduce the pesticides hazards to native honey bees (A. cerana). 10.1093/jee/toab043
Cytotoxicity, morphological and ultrastructural effects induced by the neonicotinoid pesticide, imidacloprid, using a rat Leydig cell line (LC-540). Environmental toxicology and pharmacology Imidacloprid is a systemic neonicotinoid insecticide widely used to combat agricultural pests and flea infestations in dogs and cats. Despite its low toxicity to mammals, imidacloprid is reported to cause male reproductive toxicity. This study evaluated the cytotoxic effects of 75-800 μM imidacloprid on a rat Leydig cell line (LC-540). The effect of exposure to 300, 400, and 500 µM imidacloprid on selected cytoskeletal proteins, mitochondrial morphology, lysosomal acidity, and ultrastructure were investigated. Cell viability was markedly reduced after 48 and 72 h of exposure to higher imidacloprid concentrations. The immunocytochemical analysis revealed that the cytoskeletal filaments exhibited disorganization, disruption, and perinuclear aggregation in treated LC-540 cells. Ultrastructurally, cytoplasmic vacuoles, autophagic vacuoles, lysosomes, and mitochondrial damage were detected. Changes in the mitochondrial morphology and lysosomes induced by imidacloprid were confirmed. The cytotoxicity of imidacloprid observed in LC-540 cells might be due to its mitochondrial damage and cytoskeletal protein disruption. 10.1016/j.etap.2023.104310
Assessment of Global DNA Methylation in SH-SY5Y Cells Exposed to the Neonicotinoid Insecticides Imidacloprid and Thiamethoxam. International journal of toxicology Neonicotinoid insecticides, known for their selectivity and low mammalian toxicity, have been widely used in recent years as alternatives to organophosphate insecticides. Although neonicotinoids are generally considered to be safe, data show that they can cause harmful effects on human and environmental health. Due to the lack of information on their mechanism of toxicity, the effects of imidacloprid and thiamethoxam on DNA methylation as the most used marker for epigenetic effects were investigated in human neuroblastoma (SH-SY5Y) cells. The cells were exposed to imidacloprid and thiamethoxam in concentrations of 100, 200, and 500 μM for 24 hours, then global DNA methylation and expression of genes involved in global DNA methylation (, and ) were investigated. Global DNA methylation significantly increased after imidacloprid exposure at 100 μM, and thiamethoxam exposures at 200 µM and 500 μM (>1.5-fold). Imidacloprid significantly decreased the expression of and , whereas thiamethoxam did not cause any significant changes in the expression of genes. Our findings suggested that alteration in global DNA methylation may be involved in the toxic mechanisms of imidacloprid and thiametoxam. 10.1177/10915818231154470
An integrated approach, based on mass spectrometry, for the assessment of imidacloprid metabolism and penetration into mouse brain and fetus after oral treatment. Passoni Alice,Mariani Alessandro,Comolli Davide,Fanelli Roberto,Davoli Enrico,De Paola Massimiliano,Bagnati Renzo Toxicology Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic acetylcholine receptors that shows higher affinities in insects compared to mammals. However, recent evidence show that neonicotinoids can bind to the mammalian receptors, leading to detrimental responses in cultured neurons. We developed an analytical strategy which uses mass spectrometry with multiple reaction monitoring (targeted approach) and high-resolution acquisitions (untargeted approach), which were applied to quantify imidacloprid and to identify its metabolites in biological tissues after oral treatments of mice. Mouse dams were treated with doses from 0.118 mg/kg bw day up to 41 mg/kg day between gestational days 6-9. Results showed quantifiable levels of imidacloprid in plasma (from 30.48 to 5705 ng/mL) and brain (from 20.48 to 5852 ng/g) of treated mice, proving the passage through the mammalian blood-brain barrier with a high correspondence between doses and measured concentrations. Untargeted analyses allowed the identification of eight metabolites including imidacloprid-olefin, hydroxy-imidacloprid dihydroxy-imidacloprid, imidacloprid-nitrosimine, desnitro-imidacloprid, 6-chloronicotinic acid, 5-(methylsulfanyl)pyridine-2-carboxylic acid and N-imidazolidin-2-ylidenenitramide in plasma and brain. Moreover, analysis of embryonic tissues after oral treatment of mouse dams showed detectable levels of imidacloprid (816.6 ng/g after a dose of 4.1 mg/Kg bw day and 5646 ng/g after a dose of 41 mg/Kg bw day) and its metabolites, proving the permeability of the placenta barrier. Although many studies have been reported on the neurotoxicity of neonicotinoids, our study paves the way for a risk assessment in neurodevelopmental toxicity, demostrating the capability of imidacloprid and its metabolites to pass the biological barriers. 10.1016/j.tox.2021.152935
Assessment of acetylcholinesterase, catalase, and glutathione S-transferase as biomarkers for imidacloprid exposure in penaeid shrimp. Aquatic toxicology (Amsterdam, Netherlands) Shrimp aquaculture is a valuable source of quality seafood that can be impacted by exposure to insecticides, such as imidacloprid. Here, adult black tiger shrimp (Penaeus monodon) were used to evaluate the activity of acetylcholinesterase (AChE), catalase (CAT), and glutathione S-transferase (GST) in abdominal, head, gill, and hepatopancreas tissue as biomarkers for imidacloprid exposure. Adult P. monodon were continuously exposed to imidacloprid in water (5 μgL and 30 μgL) or feed (12.5 μg g and 75 μg g) for either 4 or 21 days. The imidacloprid concentration in shrimp tissues was determined using liquid chromatography-mass spectrometry after QuEChER extraction, and AChE, CAT, and GST activities were estimated by spectrophotometric assay. Imidacloprid exposure in shrimp elevated the activity of biomarkers, and the enzymatic activity was positively correlated to tissue imidacloprid accumulation, although the effects varied in a tissue-, dose- and time-dependent manner. AChE activity was correlated to imidacloprid concentration in the abdominal tissue of shrimp and was likely related to neural tissue distribution, while the activity of CAT and GST confirmed a generalised anti-oxidant stress response. AChE, CAT, and GST were valuable biomarkers for assessing shrimp response to imidacloprid exposure from dietary or water sources, and the abdominal tissue was the most reliable for exposure assessment. An elevated response in each of these biomarkers during routine monitoring could provide an early warning of shrimp stress, suggesting that investigating potential contamination by neonicotinoid pesticides would be worthwhile. 10.1016/j.aquatox.2021.106050
Mutagenic effect of imidacloprid insecticide: The ameliorative effect of pre and post exposure to olive oil. Mohamed Wafaa H,Amein Karam A,Yahia Doha,Sharkawy Ahmed A,Mahmoud Adel S Journal of food biochemistry Imidacloprid, a systemic chloro-nicotinyl insecticide belong to neonicotinoid insecticides. In this study 120 rats were divided into four groups, the first group used as a control group, the second group was administered imidacloprid at a dose of 22.5 mg/kg b.w. for 4, 8, and 12 weeks. The third group was treated with olive oil (OLO) in a dose of 10 ml/kg body weight for 2 weeks before the oral dose of imidacloprid for 4, 8, and 12 weeks. The fourth group was given OLO in a dose of 10 ml/kg b.w. for 2 weeks after exposure to imidacloprid for 4, 8, and 12 weeks. Bone marrow was collected for micronucleus and chromosomal aberrations assays. The results revealed that imidacloprid induced a mutagenic effect in the 8 and 12 weeks of exposure and OLO decreased the mutagenic effect of imidacloprid in albino rats but not completely revert them to normal. PRACTICAL APPLICATIONS: Using OLO as a protective or therapeutic agent due to it has an ameliorative effect on mutagenicity induced by IMI. 10.1111/jfbc.13221
Effects of low-level imidacloprid oral exposure on cholinesterase activity, oxidative stress responses, and primary DNA damage in the blood and brain of male Wistar rats. Chemico-biological interactions Imidacloprid is a neonicotinoid insecticide that acts selectively as an agonist on insect nicotinic acetylcholine receptors. It is used for crop protection worldwide, as well as for non-agricultural uses. Imidacloprid systemic accumulation in food is an important source of imidacloprid exposure. Due to the undisputable need for investigations of imidacloprid toxicity in non-target species, we evaluated the effects of a 28-day oral exposure to low doses of imidacloprid (0.06 mg/kg b. w./day, 0.8 mg/kg b. w./day and 2.25 mg/kg b. w./day) on cholinesterase activity, oxidative stress responses and primary DNA damage in the blood and brain tissue of male Wistar rats. Exposure to imidacloprid did not cause significant changes in total cholinesterase, acetylcholinesterase and butyrylcholinesterase activities in plasma and brain tissue. Reactive oxygen species levels and lipid peroxidation increased significantly in the plasma of rats treated with the lowest dose of imidacloprid. Activities of glutathione-peroxidase in plasma and brain and superoxide dismutase in erythrocytes increased significantly at the highest applied dose. High performance liquid chromatography with UV diode array detector revealed the presence of imidacloprid in the plasma of all the treated animals and in the brain of the animals treated with the two higher doses. The alkaline comet assay results showed significant peripheral blood leukocyte damage at the lowest dose of imidacloprid and dose-dependent brain cell DNA damage. Oral 28-day exposure to low doses of imidacloprid in rats resulted in detectable levels of imidacloprid in plasma and brain tissue that directly induced DNA damage, particularly in brain tissue, with slight changes in plasma oxidative stress parameters. 10.1016/j.cbi.2020.109287
Imidacloprid Promotes High Fat Diet-Induced Adiposity in Female C57BL/6J Mice and Enhances Adipogenesis in 3T3-L1 Adipocytes via the AMPKα-Mediated Pathway. Sun Quancai,Qi Weipeng,Xiao Xiao,Yang Szu-Hao,Kim Daeyoung,Yoon Kyong Sup,Clark John M,Park Yeonhwa Journal of agricultural and food chemistry Imidacloprid, a neonicotinoid insecticide, was previously reported to enhance adipogenesis and resulted in insulin resistance in cell culture models. It was also reported to promote high fat diet-induced obesity and insulin resistance in male C57BL/6J mice. Thus, the goal of the present study was to determine the effects of imidacloprid and dietary fat interaction on the development of adiposity and insulin resistance in female C57BL/6J mice. Mice were fed with a low (4% w/w) or high fat (20% w/w) diet containing imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) for 12 weeks. Mice fed with imidacloprid (0.6 mg/kg bw/day) significantly enhanced high fat diet-induced weight gain and adiposity. Treatment with imidacloprid significantly increased serum insulin levels with high fat diet without effects on other markers of glucose homeostasis. AMPKα activation was significantly inhibited by 0.6 and 6 mg imidacloprid/kg bw/day in white adipose tissue. Moreover, AMPKα activation with 5-aminoimidazole-4-carboxamide ribonucleotide abolished the effects of imidacloprid (10 μM) on enhanced adipogenesis in 3T3-L1 adipocytes. N-Acetyl cysteine also partially reversed the effects of imidacloprid on reduced phosphorylation of protein kinase B (AKT) in C2C12 myotubes. These results indicate that imidacloprid may potentiate high fat diet-induced adiposity in female C57BL/6J mice and enhance adipogenesis in 3T3-L1 adipocytes via the AMPKα-mediated pathway. Imidacloprid might also influence glucose homeostasis partially by inducing cellular oxidative stress in C2C12 myotubes. 10.1021/acs.jafc.7b02584
Acute oral exposure to imidacloprid induces apoptosis and autophagy in the midgut of honey bee Apis mellifera workers. Carneiro Lenise Silva,Martinez Luis Carlos,Oliveira André Henrique de,Cossolin Jamile Fernanda Silva,Resende Matheus Tudor Cândido Santos de,Gonçalves Wagner Gonzanga,Medeiros-Santana Luanda,Serrão José Eduardo The Science of the total environment The honey bee Apis mellifera is an important pollinator that increases the yield and quality of crops. In recent years, honey bee populations have declined in some parts of the world, which has been associated with several causes, including pesticides used in agriculture. Neonicotinoids are neurotoxic insecticides widely used in the world with systemic action mode contaminating nectar and pollen that may be consumed by bees. This study evaluated the side effects of imidacloprid in the midgut of A. mellifera after acute oral exposure. Toxicity, histopathology, cytotoxicity, and expression of autophagy-related gene atg1 were evaluated in honey bee workers orally exposed to imidacloprid. The estimated imidacloprid LC was 1.44 mg L. The midgut epithelium of bees fed on imidacloprid LC has the occurrence of cytoplasm vacuoles, enlarged intercellular spaces, disorganization of the striated border, and nuclear pyknosis, with an organ injury index that increases with time exposure. The midgut digestive cells of treated bees have apical protrusions, damaged mitochondria, and autophagosomes that were characterized for content with organelle debris and high expression of atg1. These features indicate the occurrence of high cell death in the midgut of workers exposed to imidacloprid, which may affect the digestibility the physiology of the insect. 10.1016/j.scitotenv.2021.152847
Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice. Sun Quancai,Xiao Xiao,Kim Yoo,Kim Daeyoung,Yoon Kyoon Sup,Clark John M,Park Yeonhwa Journal of agricultural and food chemistry Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice. 10.1021/acs.jafc.6b04322
Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development. Wang Chao-Jie,Wang Guang,Wang Xiao-Yu,Liu Meng,Chuai Manli,Lee Kenneth Ka Ho,He Xiao-Song,Lu Da-Xiang,Yang Xuesong Journal of agricultural and food chemistry Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development. 10.1021/acs.jafc.6b01478
Enrichment of imidacloprid and its metabolites in lizards and its toxic effects on gonads. Yang Lu,Shen Qiuxuan,Zeng Tao,Li Jianzhong,Li Wei,Wang Yinghuan Environmental pollution (Barking, Essex : 1987) Soil contaminants can cause direct harm to lizards due to their regular swallowing of soil particles. As the world's fastest growing insecticide with long half-life in soil, the endocrine disrupting effect of neonicotinoids on lizards deserves more attention. In this report, we assessed the endocrine disrupting effect of imidacloprid on Eremias argus during 28 days of continuous exposure. Among the imidacloprid and its metabolites, only the metabolite 6-chloropyridic acid had a significant accumulation in the gonads and was positively correlated with its blood concentration. Imidacloprid might cause endocrine disrupting effects on lizards in two ways. First, the desnitro metabolites of imidacloprid could accumulate in the brain, inhibited the secretion of gonadotropin-releasing hormone, and ultimately affected the feedback regulation of hypothalamic-pituitary-gonadal related hormones. Secondly, imidacloprid severely inhibited the gene expression of the corresponding enzymes in the gonadal anti-oxidative stress system, causing histological damage to the gonads and ultimately affecting gonadal function. Specifically, exposure to imidacloprid resulted in abnormal arrangement of spermatogenic epithelial epithelium, hyperplasia of epididymal wall, and oligospermia of male lizard. Meanwhile, gene expressions of cyp17, cyp19, and hsd17β were severely inhibited in the imidacloprid exposure group, consistent with decreased levels of testosterone and estradiol in plasma. Imidacloprid exposure could cause insufficient androgen secretion and less spermatogenesis in male lizards. The risk of imidacloprid exposure to female lizards was not as severe as that of male lizards, but it still inhibited the expression of cyp19 in the ovaries and led to a decrease in the synthesis of estradiol. This study firstly reported the endocrine disruption of imidacloprid to lizards, providing new data for limiting the use of neonicotinoids. 10.1016/j.envpol.2019.113748
Imidacloprid Induces Histopathological Damage in the Midgut, Ovary, and Spermathecal Stored Spermatozoa of Queens After Chronic Colony Exposure. Environmental toxicology and chemistry Bee colony health is declining as a result of several factors, including exposure to pesticides. The development and strength of honey bee colonies depend on the reproductive success of queen bees. Because flowers are sources of food for bees, foragers can accidentally collect and carry contaminated pollen and nectar to their hives; and this may compromise the longevity and the life span of individuals. Thus, the present study aimed to observe the action of imidacloprid in the midgut and ovaries of Apis mellifera queens, as well as the effects on sperm stored in their spermatheca. To this end, the apiary was divided into three experimental groups: control, commercial imidacloprid, and active ingredient imidacloprid. For toxicity assays, a sucrose solution containing 1 µg/L of imidacloprid was offered to the colonies for 42 days. A control group received only food in the same period. In both treatments with imidacloprid, the midgut of queens showed modifications in the external musculature and cellular alterations. Such changes could lead to the nonrecovery of the epithelium and subsequently malabsorption of nutrients. Moreover, the digestive cells of queen bees exposed to the commercial imidacloprid presented pyknotic nuclei, suggesting a cell death process. The main alterations observed in the ovaries of these reproductive bees treated with commercial imidacloprid were degeneration and resorption of the ovariole content, which probably affected their fertilization and colony development. There were no significant changes in the spermatozoa morphology for both treatments with imidacloprid, but this insecticide may interfere with the development and reproductive success of A. mellifera colonies because it affects the morphology and function of essential organs for the survival of queens. Environ Toxicol Chem 2022;41:1637-1648. SETAC. 10.1002/etc.5332
Detection of imidacloprid and metabolites in Northern Leopard frog (Rana pipiens) brains. Campbell K S,Keller P G,Heinzel L M,Golovko S A,Seeger D R,Golovko M Y,Kerby J L The Science of the total environment Neonicotinoids are a new type of highly water-soluble insecticide used in agricultural practices to eliminate pests. Neonicotinoids bind almost irreversibly to postsynaptic nicotinic acetylcholine receptors in the central nervous system of invertebrates, resulting in overstimulation, paralysis, and death. Imidacloprid, the most commonly used neonicotinoid, is often transported to nearby wetlands through subsurface tile drains and has been identified as a neurotoxin in several aquatic non-target organisms. The aim of the present study was to determine if imidacloprid could cross the blood-brain barrier in adult Northern Leopard frogs (Rana pipiens) following exposure to 0, 0.1, 1, 5, or 10 μg/L for 21 days. Additionally, we quantified the breakdown product of imidacloprid, imidacloprid-olefin, and conducted feeding trials to better understand how imidacloprid affects foraging behavior over time. Exposure groups had 12 to 313 times more imidacloprid in the brain relative to the control and breakdown products showed a dose-response relationship. Moreover, imidacloprid brain concentrations were approximately 14 times higher in the 10 μg/L treatment compared to the water exposure concentration, indicating imidacloprid can bioaccumulate in the amphibian brain. Reaction times to a food stimulus were 1.5 to 3.2 times slower among treatment groups compared to the control. Furthermore, there was a positive relationship between mean response time and log-transformed imidacloprid brain concentration. These results indicate imidacloprid can successfully cross the blood-brain barrier and bioaccumulate in adult amphibians. Our results also provide insights into the relationship between imidacloprid brain concentration and subsequent altered foraging behavior. 10.1016/j.scitotenv.2021.152424
Imidacloprid as reproductive toxicant and endocrine disruptor: investigations in laboratory animals. Mikolić Anja,Karačonji Irena Brčić Arhiv za higijenu rada i toksikologiju Imidacloprid, a neonicotinoid insecticide, has been used worldwide due to its selective toxicity for insects. Its residues may enter the food chain, which is why it is important to investigate the potential adverse effects of imidacloprid exposure. This review summarises current knowledge of the reproductive toxicity and disruptive endocrine effects of imidacloprid in laboratory animals. Investigations, conducted mostly on laboratory rats, have shown adverse effects of imidacloprid on the reproductive ability in both parental and offspring generation as well as on the development of the offspring. Like many pesticides, imidacloprid may also act as endocrine disrupting chemical (EDC). It may disrupt the metabolic homeostasis, contribute to obesity, and disrupt steroidogenesis by inhibiting cytochrome P450 (CYP) enzyme activities. All these adverse effects of imidacloprid may pose a serious risk for reproduction and development with long-term consequences in adulthood. 10.2478/aiht-2018-69-3144