Toxicity Of Imidacloprid Research Articles

Imidacloprid: Comparative toxicity, DNA damage, ROS production and risk assessment for aquatic non-target organisms

Imidacloprid is a neonicotinoid systemic insecticide used worldwide. Despite its hazardous impact on non-target organisms, few studies have been conducted concerning the potential eco-genotoxic effects in invertebrates of surface waters where this pesticide is detected from units of ng/L to tens of μg/L. The aim of the present work was to determine the acute, the sub-chronic and the chronic toxicity of imidacloprid in producers and primary consumers of the freshwater trophic chain. The organisms under investigation were the green alga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, the cladoceran crustacean Ceriodaphnia dubia and the benthic ostracod Heterocypris incongruens. In addition, potential DNA damage and ROS production were evaluated in C. dubia.Furthermore, in accordance with European guidelines, toxicological risk assessment of imidacloprid was performed for all continents considering its global occurrence in surface waters. In addition, we assessed the genotoxicological risk and median inhibition of reproduction was observed at units of mg/L for rotifers and daphnids. Algae showed the lowest level of sensitivity to the pesticide with effective concentrations from units to hundreds of mg/L. DNA lesions were marked from 7 μg/L with a significant increase in damage as concentrations increased. Chronic toxicity risk quotient values were generally below to a threshold value of 1, with no consequential environmental concern other than for the Canadian areas. On the contrary, the genotoxicological risk quotient values were found higher than the threshold value in all continents.

Functional characterization of ABC transporters mediates multiple neonicotinoid resistance in a field population of Aphis gossypii Glover

The ATP-binding cassette (ABC) transporters C and G subfamilies have been reported to be involved in insecticide detoxification, with most studies showing increased gene transcript levels in response to insecticide exposure. Our previous studies have suggested that ABCC and G transporters participate in cyantraniliprole and thiamethoxam resistance of Aphis gossypii. In this study, we focused on the potential roles of the ABCC and G transporters of an A. gossypii field population (SDR) in neonicotinoid detoxification. The results of leaf dip bioassays showed 629.17- and 346.82-fold greater resistance to thiamethoxam and imidacloprid in the SDR strain, respectively, than in the susceptible strain (SS). Verapamil, an ABC inhibitor, was used for synergism bioassays, and the results showed synergistic effects with thiamethoxam, with synergistic ratios (SRs) of 2.07 and 6.68 in the SS and SDR strains, respectively. In addition to thiamethoxam, verapamil increased imidacloprid toxicity by 1.68- and 1.62-fold in the SS and SDR strains respectively. Then, the expression levels of several ABCC and G transporters were analyzed in different treatments. We found that the transcript levels of AgABCG4, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 were higher in the SDR strain than in the SS strain. The mRNA expression of AgABCG4, AgABCG7, AgABCG13, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 in the SDR strain was increased after thiamethoxam and imidacloprid exposure. The results of transgenic Drosophila melanogaster bioassays suggested that overexpression of AgABCG4, AgABCG7, AgABCG13, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 in transgenic flies was sufficient to confer thiamethoxam and imidacloprid resistance, and AgABCG4, AgABCG7, AgABCG13, AgABCG26 and AgMRP12 may be related to α-cypermethrin cross-resistance with weak effects. In addition, the knockdown of AgABCG4, AgABCG13, AgABCG26, AgMRP8 and AgMRP12, and the knockdown of AgABCG7 and AgABCG26 increased thiamethoxam and imidacloprid mortality in the SDR strain, respectively. Our results suggest that changes in the expression levels of ABCC and G transporters may contribute to neonicotinoid detoxification in the SDR strain, and provide a foundation for clarify the potential roles of ABCC and G transporters in insecticide resistance.

The use of sewage sludge as remediation for imidacloprid toxicity in soils.

This study investigated the influence of the sewage sludge (SS) soil amendment on the chronic toxicity of imidacloprid (through the seed dressing formulation MUCH 600 FS®-600g active ingredient L-1) to collembolans Folsomia candida. Individuals 10-12days old were exposed to two contrasting tropical soils (Oxisol and Entisol) amended with SS doses (0, 20, 40, 80, 160, and 320g SS kg-1 soil; the SS doses have low intrinsic toxicity, which was checked before its application) in a full factorial combination with five imidacloprid concentrations (varying from 0.25 to 4mgkg-1 in Oxisol and 0.03-0.5mgkg-1 in Entisol) plus a control. None of the SS doses (without imidacloprid) in both soils reduced the number of generated juvenile collembolans. The imidacloprid concentrations reducing the collembolan reproduction in 50% (EC50) in Oxisol and Entisol without SS were 0.49 and 0.08mgkg-1, respectively. However, the EC50 values generally increased with increasing SS doses in soils, varying from 1.03 to 1.41 in Oxisol and 0.07 to 0.21 in Entisol. The SS-amended soils showed 2.1- to 2.9-fold lower imidacloprid toxicity (EC50-based) in Oxisol and 1.8- to 2.7-fold lower toxicity in Entisol. Our results suggest the most effective SS doses alleviating the imidacloprid toxicity (EC50-based) to collembolans are 20gkg-1 in Oxisol and 80gkg-1 in Entisol. These results indicate that the tested SS has the potential to be employed as a soil amendment agent by reducing the toxicity of imidacloprid to the reproduction of F. candida.

Biomarkers of imidacloprid toxicity in Japanese quail, Coturnix coturnix japonica.

The in vivo effect of the oral sublethal doses of 3.014 mg kg-1 of IMI (1/25 LD50) for 1, 7, 14, and 28 days every other day on Japanese quail was investigated. The results revealed that certain biomarkers in the selected tissues of the quail such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), aminotransaminases (alanine aminotransferase, ALT, and aspartate aminotransaminase, AST), phosphatases (acid phosphatase, ACP, and alkaline phosphatase, ALP), lactate dehydrogenase (LDH), adenosine-triphosphatase (ATPase), glutathione-S-transferase (GST), lipid peroxidation (LPO), and blood glucose showed significant inductions, while significant reductions in the levels of glutathione-reduced (GSH), deoxyribonucleic acid (DNA), and ribonucleic acid (RNA) were noticed. In this study, the molecular mechanisms of the toxic effects of imidacloprid on quails were elucidated regarding neurotoxicity, hepatotoxicity, oxidative stress, lipid peroxidation, antioxidant activity, and genotoxicity. Because IMI induced alterations in the levels of these biomarkers in Japanese quail; therefore, Japanese quail as a wild avian can be used as a suite bioindicator to detect imidacloprid toxicity.

Comparing the acute and chronic toxicity of flupyradifurone and imidacloprid to non-target aquatic arthropod species

Flupyradifurone (FPF) is a new type of butenolide insecticide. It was launched on the market in 2015 and is considered an alternative to the widely used neonicotinoids, like imidacloprid (IMI), some of which are banned from outdoor use in the European Union. FPF is claimed to be safe for bees, but its safety for aquatic organisms is unknown. Its high water solubility, persistence in the environment, and potential large-scale use make it urgent to evaluate possible impacts on aquatic systems. The current study assessed the acute and chronic toxicity of FPF for aquatic arthropod species and compared these results with those of imidacloprid. Besides, toxicokinetics and toxicokinetic-toxicodynamic models were used to understand the mechanisms of the toxicity of FPF. The present study results showed that organisms take up FPF slower than IMI and eliminate it faster. In addition, the hazardous concentration 5th percentiles (HC05) value of FPF derived from a species sensitivity distribution (SSD) based on acute toxicity was found to be 0.052 µmol/L (corresponding to 15 µg/L), which was 37 times higher than IMI (0.0014 µmol/L, corresponding to 0.36 µg/L). The chronic 28 days EC10 of FPF for Cloeon dipterum and Gammarus pulex were 7.5 µg/L and 2.9 µg/L, respectively. For G. pulex, after 28 days of exposure, the no observed effect concentration (NOEC) of FPF for food consumption was 0.3 µg/L. A toxicokinetic-toxicodynamic (TKTD) model parameterised on the acute toxicity data well predicted the observed chronic effects of FPF on G. pulex, indicating that toxicity mechanisms of FPF did not change with prolonged exposure time, which is not the case for IMI.

Overexpression of ATP-binding cassette transporters ABCG10, ABCH3 and ABCH4 in Aphis craccivora (Koch) facilitates its tolerance to imidacloprid

Aphis craccivora (Koch), a globally pest that causes significant threat to the legumes, has developed different degrees of resistance to a variety of insecticides. The ATP-binding cassette (ABC) transporters comprise a multifunctional transporter protein superfamily which play important roles in the transport and detoxification of xenobiotic compounds in insects. However, whether ABC transporters take part in the tolerance of imidacloprid in A. craccivora is still unknown. In order to investigate the functions of ABC transporters in the imidacloprid tolerance, fifty- eight ABC transporters were identified in the transcriptome and genome of A. craccivora and the toxicity of imidacloprid against A. craccivora was significantly increased after application the inhibitors of verapamil and Ko143. The relative expression levels of ABCG5, ABCG6, ABCG10, ABCH3, ABCH4, ABCH8 and ABCH10 were significantly up-regulated in response to imidacloprid treatment with LC15, LC50 and LC85 concentrations, and the expression patterns of these seven ABC transporters were further analyzed at different developmental stages and in different tissues of A. craccivora by quantitative real-time PCR (RT-qPCR). Furthermore, knockdown of ABCG10, ABCH3 and ABCH4 significantly increased the mortality of A. craccivora to imidacloprid. Our results reveal the key functions of ABC transporters in the tolerance of imidacloprid and provide valuable information regarding the development of improved management strategies in A. craccivora.

Toxicity of Imidacloprid on Peripheral Blood Lymphocytes by MTT Assay and the Ameliorative Effect of Extract of Tinospora cordifolia (Gilloe) Extract

Imidacloprid (IMI) is a widely used insecticide which has a specific affinity for insect neonicotinoid acetylcholine receptors. Like all insecticides which are used in excess it tends to bioaccumulate in the environment. So it was thought worthwhile to study its cytotoxicity to human peripheral blood lymphocytes in concentrations ranging from 1.5mM to 4mM after 2 hours and 18 hours exposure by MTT method. Trypan blue test was also used to determine the percentage of living cells. The ameliorative effect of an extract of the stem in water and ethanolic extract of leaves of Tinospora cordifolia (Thunb.) Miers, was also studied. The viability of the lymphocytes showed a fall with increasing concentrations at an exposure of 2 hours. After 18 hours exposure to the IMI only, the viability showed a significant dose dependent drop. Trypan blue test for viability was also conducted. Addition of Tinospora extract raised the viability significantly at 2 hours of incubation. In fact this increase was greatest at 3.5mM and 4mM concentration of drug. The ameliorative effect was maximum at 2 hours. Addition of Tinospora leaf extract showed a significant increase in cell viability at 18 hours of incubation as compared to values obtained with only the drug. Thus a considerable loss of viability of lymphocytes was seen after exposure to the drug in the selected concentrations but herbal extracts seem to help to make the damage less marked. The cells showed a significant rise in viability when incubated with Tinospora leaf extract only, confirming its supportive action in cell proliferation. However, taking into account the evident fall in cell viability caused by exposure to the considerably dilute concentrations tested, caution is needed to prevent over exposure to the pesticide while spraying.

The endoplasmic reticulum-mitochondrial crosstalk is involved in the mitigation mechanism of eucalyptol on imidacloprid toxicity in Ctenopharyngodon idellus kidney cells

Imidacloprid (IMI), a systemic neonicotinoid insecticide widely used in agriculture, resulting in persistence in aquatic environments that threaten the survival of organisms. Eucalyptol (EUC), a monoterpenoid found in plants, can be applied to medicine, food, and aquaculture. However, the potential protective effects of EUC on cell damage under neonicotinoid pesticide toxicity, and the role of ER stress and its mediated apoptosis and necroptosis in it, remain unclear. Therefore, we treated Ctenopharyngodon idellus kidney (CIK) cells with 20 mg/L IMI and 20 μM EUC for 48 h. The results showed that IMI exposure caused a higher GRP78 levels, activated ATF6, PERK-eIF2α and IRE1-XBP1 pathways, led to the decline of ATPase activities and ATP content, induced the expression of cytokine (TNF-α, IL-1β, IL-6 and INF-γ), triggered BCL2/BAX-mediated apoptosis and RIP1/RIP3/MLKL-dependent necroptosis in the CIK cell line. Surprisingly, EUC had an effect against IMI-induced cytotoxicity, showing that it effectively mitigated the above-mentioned IMI-exposure-induced changes. Taken together, these results suggested that EUC could alleviated IMI-induced cell death and dysimmunity by recovering ER stress/mitochondria imbalance. These results partly explained the mechanism of biological threat on fish under IMI exposure and the potential application value of EUC in aquaculture.

Toxicity and Residual Activity of Insecticides against Diadegma insulare, a Parasitoid of the Diamondback Moth.

Simple SummaryThe diamondback moth is an insect pest that feeds on broccoli, cauliflower, cabbage, and other related plants. When its population increases, it can cause significant damage to those crops and economic losses to farmers. The fastest way to control this pest is by applying insecticides; however, the pest has become resistant to many of them. Therefore, it has been necessary to use higher doses of insecticides to decrease its population over time. At the same time, insecticides affect the pest’s natural enemies, which are essential to keeping pest populations low. Diadegma insulare is a tiny wasp that lays its eggs and develops inside the larvae of the diamondback moth, and kills it. This wasp is an important parasitoid of the pest and is found naturally in crop fields; it has also been introduced in some countries worldwide. In this research, we identified insecticides that are least toxic to D. insulare. If farmers have this information, they can choose products to kill the pest and reduce the impact of those products on natural field populations of D. insulare. By using the least toxic or residual insecticides, farmers will keep and increase the role of D. insulare as a natural enemy of the diamondback moth.Plutella xylostella is the main pest of cruciferous crops worldwide. To reduce P. xylostella populations, better integration of natural control and chemical control (dominant tactic used) is needed. This work analyzed the compatibility of nine insecticides with the parasitoid Diadegma insulare, outlining them as complementary tools in an integrated pest management strategy. The acute toxicity of spinosad, imidacloprid, indoxacarb, flonicamid, naled, pyridalyl, emamectin benzoate, and spinetoram against the parasitoid was assessed. Residual activity (persistence) was also evaluated over time; the mortality of the parasitoid in contact with leaf tissue of plants treated with insecticides was analyzed. According to the International Organization of Biological Control, all nine insecticides were toxic to D. insulare; the lowest mortality was recorded with spirotetramat (64%) and pyridalyl (48%), while the rest of the insecticides caused 100% mortality at 72 h after application. In terms of persistence, by days 14, 16, 16, 17, 17, 21, and 22 after application, flonicamid, naled, spirotetramat, spinosad, piridalyl, imidacloprid, and indoxacarb caused mortality of less than 25%, respectively, so they were considered harmless (Category 1). Nonetheless, some insecticide toxicity and residual activity must be regarded within integrated pest management programs for conserving the role of D. insulare field populations.

Melatonin enhances the antioxidant capacity to rescue the honey bee Apis mellifera from the ecotoxicological effects caused by environmental imidacloprid

Imidacloprid severely poisons the nontarget insect honey bee Apis mellifera. Few treatments are available to mitigate the adverse effects of imidacloprid. The primary concern is that the molecular understanding of imidacloprid toxicity is not comprehensive enough. Oxidative stress is the primary pathophysiological mechanism by which pesticides cause high mortality. Our pilot study found for the first time that imidacloprid stimulates bee brains to secrete melatonin, a free radical scavenger. However, the molecular basis for imidacloprid toxicity and the role of melatonin in coping with imidacloprid have not been systematically investigated in bees. This study administered an environmental dose of imidacloprid (36 ng/bee) orally to A. mellifera. The detoxification gene cytochrome P450 CYP4G11 was significantly induced. However, potent cytotoxicity of imidacloprid suppressed the expression of the antioxidants catalase (CAT) and thioredoxin reductase (TrxR), and the activity of guaiacol peroxidase (GPX), superoxide dismutase (SOD), and reduced glutathione (GSH) was not induced. The levels of reactive oxygen species (ROS) and the lipid peroxidation marker malondialdehyde (MDA) were increased. The expression of the apoptotic genes cysteinyl aspartate specific proteinase (Caspase-3) and apoptosis inducing factor (AIF) increased, and the apoptotic features of midgut cells were prominently apparent. These results suggest that imidacloprid disrupts the bee antioxidant system, causing severe oxidative stress and tissue damage and ultimately leading to apoptosis. Significantly, however, imidacloprid exposure also stimulated bee brains to continuously secrete melatonin. Further preadministration of exogenous melatonin (200 ng/bee) orally to bees significantly reversed and enhanced the activity of the imidacloprid-suppressed antioxidants CAT, SOD, and GSH, which allowed imidacloprid-induced ROS accumulation to be effectively alleviated. The MDA content, apoptotic genes Caspase-3 and AIF, and detoxification gene CYPG411 expression were restored to normalization; midgut cell damage, apoptosis, and mortality were significantly reduced. These findings strongly suggest that melatonin enhanced bee antioxidant capacity, thus attenuating oxidative stress and apoptosis to confer imidacloprid tolerance to honey bees. Melatonin secretion may be a defense mechanism to mitigate imidacloprid toxicity.

The Toxicity of Imidacloprid on Early Embryonic Stages and Growth Rate of Hatchlings of Common Carp, <i>Cyprinus carpio</i>

In the present investigation, the toxicity of imidacloprid was tested on the embryos (fertilized eggs) and hatchlings of Cyprinus carpio in terms of mortality (%), hatching success (%) and abnormal/malformed hatchling along with their growth performance in toxicant medium. Reported data from acute toxicity tests of imidacloprid was statistically analyzed by Probit Analysis Method and 48 h (hour) LC50 was reported as 78 ppm for embryos of C. carpio. Three sublethal doses of imidacloprid i.e., 7.8 ppm (T1), 15.6 ppm (T2) and 23.4 ppm (T2), were selected for further experimentation along with control. The findings revealed that mortality of exposed eggs (%) was significantly (p<0.05) increased in dose dependent manner as a result hatching rate (%) was decreased as compared to control. Similarly, per cent of abnormal hatchling was also increased significantly (p<0.05) with increase in pesticide concentration. Various types of abnormalities has been reported in different body regions such as whole length curved body, stunted growth, hatchling with single eye, malformed head, flexure in the tail and deformed yolk sac etc. Growth rate was observed as length gain in centimeter (cm), weight gain in grams (g) and growth per cent gain in body weight of hatchling, which was also found to be declined significantly (p<0.05) with increase in pesticide concentration. The findings of the present investigation suggest that imidacloprid has significant effect on the early developmental stages, induces malformations and also decline the growth rate of hatchlings.

The effects of imidacloprid on 8-hydroxy-2-eoxyguanosine (8-OHdG) and antioxidant parameters in gill and liver tissues of trout

ABSTRACT In this research, it was aimed to determine the effects of imidacloprid on 8-hydroxy-2-deoxyguanosine (8-ohdg) and antioxidant parameters in the liver and gill tissues of rainbow trout (Oncorhynchus mykiss). Three different concentrations (5 mg/L, 10 mg/ L and 20 mg/L) of the imidacloprid were routinely exposed to rainbow trout for 21 days. Antioxidant enzymes, malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHDG) were studied in the samples. In the 5 mg/L experimental group, it was determined that CAT values and liver GPx and SOD levels increased compared to those in the control group. It was found that there were significant increases between 5 mg/L and 10 mg/L dose groups of MDA, 8-OHdG, liver GPx-SOD and gill CAT-GPx enzyme activities (p < 0.05). High increases in all antioxidant enzyme levels were observed in liver and gill tissues of fish exposed to 20 mg/L dose imidacloprid. 8-OHdG and MDA levels significantly increased in parallel with the increase in the dose (p <0.05). These results suggested that imidacloprid can be toxic to fish by leading to an increase in 8-OHdG activity and changes in oxidative stress parameters. Therefore, these data may reflect one of the molecular pathway that play roles in imidacloprid toxicity.

Imidacloprid toxicity in Clarias gariepinus: Protective role of dietary Hyphaene thebaica against biochemical and histopathological disruption, oxidative stress, immune genes expressions, and Aeromonas sobria infection

Recently, there has been a controversy about the hazards of toxic substances released to the aquatic biota. Therefore, the current context is the first attempt to assess the ability of a beneficial medicinal plant, Hyphaene thebaica fruit (HTF) to mitigate various toxic impacts in Clarias gariepinus induced by imidacloprid (IMI) including immune depression, protein impairment, oxidative stress, hepato-renal dysfunction, histopathological, and immune-histochemical alterations. The molecular responses of IMI-induced toxicity at the molecular level and to recognize critical genes altered in response to toxicity are documented. Additionally, we investigated the fish resistance post-challenging with a pathogenic zoonotic bacterium, Aeromonas sobria. Fish (N = 240) were randomly allotted into four random groups in triplicate. The first (control) and second (HTF) groups were fed on basal diets that were enriched with 0.0 and 15 g kg−1 of HTF without IMI exposure. The third and fourth groups were fed on the same diets and exposed to 1/5 of the 96-h of LC50 of IMI (2.03 μg L−1) for 60 days. The findings clarified that the IMI exposure significantly augmented (p < 0.05) serum alanine (ALT), aspartate amino-transferases (AST), urea, and creatinine besides malondialdehyde (MDA) levels. While the activities of the protein profile (total protein, albumin, and globulin), immune parameters (lysozyme and immunoglobulin M), and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) revealed marked depressions in comparison to the control. Histological and immune-histochemical alterations in liver and kidney tissues including vacuolation, severe necrosis, and degeneration, besides weak B-cell lymphoma 2 (BCL-2), potent caspase-3, and down-regulation of genes (IL-1β, IL-8, TNF-α, TGF-β, TLR-5, LYSG, LYSC, NF-κβ, CC, and MYE) were noticed in the IMI-exposed group compared to the control. After 60 days of experimental trial, C. gariepinus challenged by A. sobria exhibited sluggish movement, fin rot accompanied with hemorrhages in different body parts, and severe skin ulcerations with the highest cumulative mortality (80%). Surprisingly, HTF-dietary inclusion enhanced these variables by almost renovating to control values by maintaining histological architecture of the hepatic and renal tissues. Additionally, it increased the fish resistance against A. sobria indicated by reduced mortalities (40%) and enhanced clinical picture. The outputs of the recent study recommend the HTF-dietary supplement to protect against the IMI toxicity in C. gariepinus. And provide insights into the future application of the HTF as an anti-toxic, immune-stimulant, antioxidant, and antibacterial, for improving fish health and sustaining aquaculture. To avoid the deleterious toxic impacts of IMI, this pesticide must be applied carefully, especially near water bodies.

Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats

Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn’t been mentioned previously as well as the toxicity of HFM doesn’t elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM–evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats’ body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-ὰ, and NF-KB protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-KB signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.

Assessment of Genotoxicity, Hepatotoxicity and Reproductive Toxicity of Imidacloprid on Mammalian Models

Imidacloprid, a systemic neonicotinoid insecticide, isused widely to control various types of harmful insects and pests to prevent crop damage. Use of imidacloprid was increased tremendously in last few decades due to its lowtoxicityon mammals/vertebrates. Consistent use of Imidacloprid in enormous amount showed evidences of toxicity in exposed non-target invertebrates vertebrates and also in mammals. This review focuses on the extent of toxicity induced at genetic, biomolecular, biochemical and histological level due to exposure of imidacloprid on mammalian models. Various parameters like antioxidant enzyme assays, cytotoxic assays, hematological parameters, histological parameters and reprotoxic assays are used to evaluate the toxicity of imidacloprid in mammalian models. Imidacloprid may damage DNA, alter histology and disturb antioxidant system of the body. The outcome will help in better understanding of imidacloprid toxicity on mammalian systems.

Ferroptosis and Oxidative Damage Mediated the Size-Dependent Combined Toxicity of Microplastics and Imidacloprid on Earthworm(Eisenia Fetida)

Ferroptosis and Oxidative Damage Mediated the Size-Dependent Combined Toxicity of Microplastics and Imidacloprid on Earthworm(Eisenia Fetida)

Low Doses of Imidacloprid Induce Oxidative Stress and Neural Cell Disruption in Earthworm &lt;i&gt;Eisenia fetida&lt;/i&gt;

Imidacloprid is a widely used pesticide that belongs to the class of neonicotinoids. There is a piece of rising evidence that neonicotinoids exert cytotoxic effects in non-target organisms including vertebrate species such as mammals. Nevertheless, dose-limiting toxicity and molecular mechanisms of neonicotinoids' deleterious effects are still poorly understood. In accord to imidacloprid fate in the environment, the most of used pesticide is absorbed in the soil. Therefore, earthworms, which are prevailing soil organisms, could be considered as a target of neonicotinoids toxicity. The earthworm’s simple nervous system is a prospective model for neurotoxicological studies. We exposed earthworms to imidacloprid in a paper contact test with a doses range of 0.1‑0.4 µg/cm2 for 14 days. In the present work, we studied the imidacloprid effect on oxidative stress generation and neuronal marker neuron-specific enolase (NSE) expression. The exposure to imidacloprid induced a dose-dependent decrease in NSE. Both reactive oxygen species production and lipid peroxidation level were upregulated as well. Observed NSE decline suggests imidacloprid-caused disturbance in earthworm neuron cells. Obtained data have shown that relatively low doses of imidacloprid are potent to induce cytotoxicity in neurons. Furthermore, neurotoxicity could be recognized as one of an individual scenario of the general imidacloprid toxicity. Thus, presented results suggest the cytotoxicity of imidacloprid low doses in non-target organisms and hypothesize that NSE downregulation could be estimated as a biomarker of neonicotinoid cytotoxicity in a nervous system of non-insect species.

Low Doses of Imidacloprid Induce Oxidative Stress and Neural Cell Disruption in Earthworm &lt;i&gt;Eisenia fetida&lt;/i&gt;

Imidacloprid is a widely used pesticide that belongs to the class of neonicotinoids. There is a piece of rising evidence that neonicotinoids exert cytotoxic effects in non-target organisms including vertebrate species such as mammals. Nevertheless, dose-limiting toxicity and molecular mechanisms of neonicotinoids' deleterious effects are still poorly understood. In accord to imidacloprid fate in the environment, the most of used pesticide is absorbed in the soil. Therefore, earthworms, which are prevailing soil organisms, could be considered as a target of neonicotinoids toxicity. The earthworm’s simple nervous system is a prospective model for neurotoxicological studies. We exposed earthworms to imidacloprid in a paper contact test with a doses range of 0.1‑0.4 µg/cm2 for 14 days. In the present work, we studied the imidacloprid effect on oxidative stress generation and neuronal marker neuron-specific enolase (NSE) expression. The exposure to imidacloprid induced a dose-dependent decrease in NSE. Both reactive oxygen species production and lipid peroxidation level were upregulated as well. Observed NSE decline suggests imidacloprid-caused disturbance in earthworm neuron cells. Obtained data have shown that relatively low doses of imidacloprid are potent to induce cytotoxicity in neurons. Furthermore, neurotoxicity could be recognized as one of an individual scenario of the general imidacloprid toxicity. Thus, presented results suggest the cytotoxicity of imidacloprid low doses in non-target organisms and hypothesize that NSE downregulation could be estimated as a biomarker of neonicotinoid cytotoxicity in a nervous system of non-insect species.

Synergistic effect of ZnO NPs and imidacloprid on liver injury in male ICR mice: Increase the bioavailability of IMI by targeting the gut microbiota

Although many toxicological studies on pesticides and nanoparticles have been conducted, it is not clear whether nanoparticles will increase the toxicity of pesticides. In this study, we chose imidacloprid (IMI) as a representative pesticide, and explored the influence of ZnO NPs on the toxic effect of IMI. In addition, we studied the bioaccumulation of IMI in mice. Using biochemical index analysis, liver histopathological analysis, non-targeted metabolomics, and LC/MS analysis, we found that ZnO NPs increased the toxicity of IMI, which may be related to the increase in IMI bioaccumulation in mice. In addition, we used intestinal histopathological analysis, RT-qPCR, and 16sRNA sequencing to find that the disturbance of the gut microbiota and the impaired intestinal barrier caused by ZnO NPs may be the reason for the increase in IMI bioaccumulation. In summary, our results indicate that ZnO NPs disrupted the intestinal barrier and enhanced the bioaccumulation of IMI, and therefore increased the toxicity of IMI in mice. Our research has deepened the toxicological insights between nanomaterials and pesticides.

Imidacloprid activates ROS and causes mortality in honey bees (Apis mellifera) by inducing iron overload

Imidacloprid, a neonicotinoid pesticide widely used for insect pest control, has become a potential pollutant to pollinators. Previous reports have demonstrated the toxicity of this drug in activating oxidative stress resulting in high mortality in the honey bee Apis mellifera. However, the mechanisms underlying the toxicity of imidacloprid have not been fully elucidated. In this study, sublethal (36 ng/bee) and median lethal (132 ng/bee) doses of imidacloprid were administered to bees. The results showed dose-dependent increases in reactive oxygen species (ROS), Fe2+, and mortality in bees. Notably, imidacloprid also induced upregulation of the gene encoding ferritin (AmFth), which plays a pivotal role in reducing Fe2+ overload. Upregulation of AmFth has been suggested to be closely related to ROS accumulation and high mortality in bees. To confirm the role played by AmFth in imidacloprid-activated ROS, dsAmFth double-strand was orally administered to bees after exposure to imidacloprid. The results revealed aggravated Fe2+ overload, higher ROS activation, and elevated mortality in the bees, indicating that imidacloprid activated ROS and caused mortality in the bees, probably by inducing iron overload. This study helps to elucidate the molecular mechanisms underlying the toxicity of imidacloprid from the perspective of iron metabolism.