Abamectin Research Articles

Genome-wide identification, characterization, and expression profiling of ATP-binding cassette (ABC) transporter genes potentially associated with abamectin detoxification in Cydia pomonella

The codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) is one of the most notorious pests of pome fruits and walnuts worldwide, which has developed resistance to almost all classes of insecticides, including abamectin (ABM). ATP-binding cassette (ABC) transporters are thought to play a vital roles in insecticide detoxification by reducing the toxic concentrations of insecticides in an organism tissues. Despite the tremendous progress in understanding the detoxification mechanisms at the molecular level, the physiological functions of ABC transporters in insects have been poorly investigated. In this study, we found that the ABC inhibitor verapamil synergized significantly the toxicity of ABM, suggesting a potential role of ABC in detoxification. A total of 54 ABC genes were identified in the third-instar larvae of C. pomonella after treatment with sublethal doses (LD10 and LD30) of ABM. The expression profile of these genes in ABM-treated larvae at different time points (24, 48, 72 hr) using transcriptomic analysis (RNA-seq) was also investigated. The results showed that the expression of about 30 ABC genes was significantly co-upregulated after treatment. Several specific genes were up-regulated at 48 hr after treatment of larvae with LD10 ABM. Among these up-regulated genes, we found that the relative expression level of the CPOM19553 was 29.7-fold and 16.0-fold higher when larvae were exposed to ABM at the LD10 and LD30 doses compared to control, respectively. Unlike other ABC genes, only CPOM08323 exhibited significant expression levels in the head and cuticle of the third-instar larvae of C. pomonella exposed to the two sublethal doses of ABM, with no expression was observed in the detoxification tissues such as midgut and Malpighian tubule. This study suggests that these up-regulated genes may be involved in ABM resistance in C. pomonella. Our findings will provide an additional information required for further analysis of ABC transporter genes associated with xenobiotic metabolism in C. pomonella.

Efficacy of combined treatments of abamectin with three inert dusts for the control of Callosobruchus chinensis on cowpea seeds

The insecticidal efficacy of abamectin (AB) and three inert dusts, diatomaceous earth (DE), zeolite (ZE) and kaolin (KA), was evaluated alone and in binary mixtures as stored cowpea protectants against Callosobruchus chinensis. Inert dusts (DE, ZE and KA) were tested at 100, 500 and 1000 mg/kg (ppm), and abamectin was applied at 0.1, 0.25 and 0.5 mg/kg (ppm). Adult mortality of C. chinensis was evaluated after 3 and 7 days of treatment, while progeny production and cowpea seed weight loss were recorded for all tested treatments after 60 days. The mortality of adults in the binary treatments was higher than the individual treatments of inert dusts or AB. Combined treatments of AB at 0.5 mg/kg with DE, ZE or KA at 500 and 1000 mg/kg led to 100% mortality after 7 days of treatment. Moreover, combined treatments of AB (0.25 mg/kg) with KA (1000 mg/kg), AB (0.25 mg/kg) with ZE (1000 mg/kg) and AB (0.5 mg/kg) with KA (100 mg/kg) caused 100% mortality of adults after 7 days of treatment. After 3 days, the binary mixture of AB (0.5 mg/kg) with KA (1000 mg/kg) was the only treatment inducing 100% adult mortality. All treatments with inert dusts, AB, and their binary mixtures caused significant decrease in progeny production of C. chinensis after 60 days of exposure. In particular, treatments with high concentrations induced strong progeny reduction and led to complete protection of cowpea seeds against weight loss and damage caused by C. chinensis after 60 days. Furthermore, no adverse effect on germination was observed in cowpea seeds treated with the highest application rates of inert dusts, AB, and their mixtures. Our findings demonstrated that binary mixtures of inert dusts with abamectin could be successfully used as potential protectants for cowpea seeds against C. chinensis.

Cyathostomin resistance to moxidectin and combinations of anthelmintics in Australian horses

BackgroundCyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses.MethodsTwo drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins.ResultsOf the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of − 41% (− 195% lower confidence limit [LCL]), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively.ConclusionsThis study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics.Graphical

Identification and pharmacological characterization of histamine-gated chloride channels in the fall armyworm, Spodoptera frugiperda

Histamine-gated chloride channels (HACls) mediate fast inhibitory neurotransmission in invertebrate nervous systems and have important roles in light reception, color processing, temperature preference and light-dark cycle. The fall armyworm, Spodoptera frugiperda is a main destructive pest of grain and row crops. However, the pharmacological characterization of HACls in S. frugiperda remain unknown. In this study, we identified two cDNAs encoding SfHACl1 and SfHACl2 in S. frugiperda. They had similar expression patterns and were most abundantly expressed in the head of larvae and at the egg stage. Electrophysiological analysis with the two-electrode voltage clamp method showed that histamine (HA) and γ-aminobutyric acid (GABA) activated inward currents when SfHACls were singly or collectively expressed with different ratios in Xenopus laevis oocytes. These channels were ≥2000-fold more sensitive to HA than to GABA. They were anion-selective channels, which were highly dependent on changes in external chloride concentrations, but insensitive to changes in external sodium concentrations. The insecticides abamectin (ABM) and emamectin benzoate (EB) also activated these channels with the EC50 to SfHACl1 lower than that to SfHACl2. And the EC50s of ABM and EB to the co-expressed channels gradually increased with increase in the injection ratio of SfHACl2 cRNA. Homology models and docking simulations revealed that HA bound to the large amino-terminal extracellular domain of SfHACl1 and SfHACl2 by forming 4 and 2 hydrogen bonds, respectively. The docking simulations of ABM and EB had similar binding sites in the transmembrane regions. Overall, these findings indicated that HACls act as targets for macrolide, and this study provides theoretical guidance for further derivatization of abamectin insecticides.

Investigation of the effects of hesperidin administration on abamectin-induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways.

In this study, the potential effects of hesperidin (HES) on chronic toxicity caused by abamectin (ABM) in the testicular tissue were investigated through oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy pathways. Male Sprague Dawley rats were used in the study. Animals in the ABM group were orally administered 1 mg/kg ABM every other day for 28 days, while HES used against ABM was given at 100 or 200 mg/kg 30 min after ABM administration for 28 days. Markers of oxidative stress, inflammation, ERS, apoptosis, and autophagy in the testicular tissues removed after the animals are sacrificed were analyzed using biochemical, real-time polymerase chain reaction (RT-PCR), or western blot techniques. The results obtained showed that ABM caused oxidative stress, and triggered ERS, inflammation, apoptosis, and autophagy. On the other hand, HES showed antioxidant effect by increasing superoxide dismutase, catalase, glutathione peroxidase enzyme activities, and glutathione levels in testis tissue and attenuated lipid peroxidation. Accordingly, MAPK14 reduced the NF-κB, IL-1β, TNF-α, and IL-6 expression levels, presenting an anti-inflammatory effect. In addition, Bax protected against apoptosis and autophagy by reducing the caspase-3, beclin-1, LC3A, and LC3B expressions, and increasing Bcl-2 expression. It was observed that HES also interrupted the JAK2/STAT3 signaling pathway by suppressing IL-6 expression. Taken into consideration together, HES provided significant protection against the destruction caused by ABM in testicular tissue with antioxidant, anti-inflammatory, antiapoptotic, and anti-autophagic effects. Thus, it was revealed that HES has the potential to serve as an alternative treatment option in ABM toxicity.

The effect of polyethylene terephthalate and abamectin on oxidative damages and expression of vtg and cyp1a genes in juvenile zebrafish

Increasing the abundance and wide distribution of microplastics is one of the most important concerns of biological communities. These particles can act as carriers of environmental chemical pollutants and pesticides. Absorption of these particles by living organisms, especially aquatic organisms, may cause changes in the gene expression as well as enzymes activity in the antioxidant pathway. In this study, combined and individual effects of polyethylene terephthalate (PET) microplastics, as one of the most widely used plastics in industry, and abamectin (ABM) pesticide was evaluated on glutathione content, total antioxidant capacity, free radical scavenging, vitellogenin (vtg) and cytochrome P450, family 1, subfamily a (cyp1a) gene expression in zebrafish. The results indicated that microplastics (MPs) in combination with pesticides reduced the content of glutathione. The gene expression of cyp1a showed significant decreased in zebrafish after treatment with ABM alone and in combination with microplastic, while the expression of vtg gene was significantly increased in samples treated with combination of ABM and MPs. Analysis of antioxidant activity revealed that glutathione content, glutathione peroxidase and DPPH activity were not affected by MPs when applied alone, but it increased the total antioxidant capacity and also inhibited the superoxide dismutase (SOD) activity. ABM had no effect on glutathione peroxidase and DPPH activity, but it reduced SOD activity. Also, the combination of microplastic and toxin increased glutathione peroxidase activity and decreased the glutathione content, SOD and DPPH activity. In general, the result of this study demonstrated that the effect of MPs cannot be ignored in increasing the toxicity of other pollutants.

Residue kinetics of neonicotinoids and abamectin in pistachio nuts under field conditions: model selection, effects of multiple sprayings, and risk assessment.

Pistachio is an economically valuable crop, and Iran is among the biggest producers, exporters, and consumers of this product in the world. During the growing season, pistachios are subjected to multiple sprayings with various pesticides, which result in the accumulation of their residues in nuts. These residues have raised concerns regarding consumers' health. In this research, uptake and dissipation kinetics of insecticides imidacloprid (IMI), thiacloprid (THI), thiamethoxam (THX), and abamectin (ABA) were investigated in pistachio nuts. Field experiments were conducted in a pistachio orchard. Pistachio trees were sprayed with the recommended dose of each insecticide formulation and water as the control. Samplings were performed for up to 49 days. Based on the results, pesticides uptake and dissipation kinetics were best fitted to first-order exponential growth (FOEG) and single first-order kinetic (SFOK) models, respectively. Variations in pesticides uptake/dissipation rates were mostly related to their water solubility, pKa, and log Kow. THX showed a higher uptake rate (0.16 ± 0.04) compared to IMI (0.10 ± 0.01) and THI (0.06 ± 0.01). The fastest dissipation rates were observed for IMI (0.04 ± 0.002 day-1) and THX (0.03 ± 0.001 day-1), while the slowest belonged to THI (0.02 ± 0.003 day-1). ABA residues were below the quantification limit (LOQ) throughout the experiment. Based on FOEG and SFOK model predictions, multiple sprayings with THI and THX resulted in final concentrations exceeding the maximum residue limit (MRL). Hazard quotients for all pesticides were <1, indicating no risk to humans via consumption of the pistachio nut.

Ivermectin: A Promising Therapeutic for Fighting Malaria. Current Status and Perspective.

Finding new chemotherapeutic interventions to treat malaria through repurposing of time-tested drugs and rigorous design of new drugs using tools of rational drug design remains one of the most sought strategies at the disposal of medicinal chemists. Ivermectin, a semisynthetic derivative of avermectin B1, is among the efficacious drugs used in mass drug administration drives employed against onchocerciasis, lymphatic filariasis, and several other parasitic diseases in humans. In this review, we present the prowess of ivermectin, a potent endectocide, in the control of malaria through vector control to reduce parasite transmission combined with efficacious chemoprevention to reduce malaria-related fatalities.

Comparative toxicity of abamectin and nano-derived form on land snail, Helix aspersa in attributing to cytotoxicity and biochemical alterations

The comparative toxic effect of Vertimec® 1.8% EC, Fast Max Super® 8.4% SC and nano-derived form of abamectin (ABM) (1% nano-emulsion) as a dermal contact for 48 h against land snail, Helix aspersa was evaluated at laboratorial trail. Acute toxicity values (LD50) were 6.45, 11.97, and 45.95 µg snail-1 for nano-derived form of ABM, Fast Max Super® and Vertimec®, respectively. Nano-derived form exhibited the highest toxic effects (1.86 and 7.12-folds), respect to Fast Max Super® and Vertimec®. Sublethal doses: 1/10 and 1/100 LD50s of the examined compounds were applied to evaluate some biochemical alterations e.g. acetylcholinesterase (AChE), malondialdhyde (MDA), lactate dehydrogenase (LDH), glutathione-S-transferase (GST), acid phosphatase (ACP), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), respectively, in haemolymph and digestive glands homogenates. The all treatments significantly decreased AChE activity in ganglia homogenate, respect to control group (untreated). All treatments exhibited MDA level and LDH activity greater than the control in both haemolymph and digestive gland. This concept recognizes the cytotoxic effect of ABM on gastropods. Significant declines in GST, ACP, and ALP activities were exhibited in homogenate of digestive gland for the all treatments. However, AST/ALT activities exhibited increase greater than untreated group. These findings may explain the role of these doses of ABM for dysfunction in organs of H. aspersa. Thus, prepared nano-emulsion was more potent toxic on land snails. However, H. aspersa is considered a useful tool to assess ecotoxicological impact of pesticides.

High temperature stress induces expression of CYP450 genes and contributes to insecticide tolerance in Liriomyza trifolii

Liriomyza trifolii is an invasive leafminer fly that inflicts damage on many horticultural and vegetable crops. In this study, the effects of elevated temperatures on L. trifolii tolerance to insecticides abamectin (AB), monosultap (MO) and a mixture of abamectin and monosultap (AM) were firstly investigated, then five CYP450 genes (LtCYPs) were cloned, and expression patterns and NADPH cytochrome C reductase (NCR) activity in L. trifolii were compared in response to high temperature stress and insecticide exposure. Results showed elevated temperatures induced expression of LtCYP450s, the expression level of LtCYP4g1, LtCYP4g15 and LtCYP301A1 after exposed to different high temperature were significantly up-regulated compared with the control (25 °C), while there was no significant difference in LtCYP4E21 and LtCYP18A1. Under the joint high temperature and insecticide stress, the expression of LtCYP4g15, LtCYP18A1 and LtCYP301A1 was significantly higher under elevated temperatures than that of only under AB exposure. For MO and AM exposure, only 40 °C could induce the expression of LtCYP4g15, LtCYP18A1 and LtCYP301A1. In general, the LtCYPs expression pattern was correlated with increased NCR activity and decreased mortality in response to insecticide exposure under elevated temperatures. These all demonstrated that insecticide tolerance in L. trifolii could be mediated by high temperature. This study improves our understanding of L. trifolii physiology and offers a theoretical context for improved control that ultimately reduces the abuse of insecticides and decreases exposure to non-target organisms.

Acute Abamectin Exposure Induces Oxidative Stress Responses in Liver of Male Albino Rats

Background: Acute oral and dermal toxicity tests are considered as a regulatory assessment in systemic toxicity of agrochemicals. Aim: this study achieved to study the effect of single oral and dermal sub-lethal exposure of abamectin on the oxidative stress biomarkers in the liver of male albino rats. Methods: forty rats were divided into three groups as control, oral and dermal. The tested dose was ½ of LD50 for oral and dermal experiments. Results: exposure to abamectin (ABM) at sub-lethal doses oral or dermal is connected with induction of oxidative stress in the liver of male albino rats. Oxidative stress is evidenced by the increase in lipid and protein oxidation (MDA and PC) biomarkers. As well, antioxidant enzymes such as CAT and GST were increased hepatocytes. On the other hand, glutathione and glutathione peroxidase (GPx) and SOD were markedly reduced. Acetylcholinesterase (AChE) activity in hepatocytes was markedly increased in both oral and dermal exposure. Conclusion: this study through light on the importance of responsible use of pesticides in reducing the hazard impact of agrochemicals.

Nanostructured Insecticide Composition through the Incorporation of Natural Abamectin in β-Cyclodextrin: Activity against Aedes aegypti Larvae

This study searched for a new pre-formulation based on the natural compound from the class of the avermectins, named abamectin (ABA), in order to improve its action against Aedes aegypti larvae by complexation with β-cyclodextrin (βCD). Concerning the low aqueous solubility of ABA, even in the presence of βCD, it was also invoked the strategy of working with hydrophobic nanoprecipitates (HNPs). For these purposes, molecular and supramolecular characterizations of 1:1 ABA/βCD complex and evaluation of its toxicity against A. aegypti larvae were performed. In the physical-chemistry characterizations, changes in the infrared spectra and thermal profiles in relation to precursors confirmed the occurrence of interactions between ABA and βCD in solid state. Nuclear magnetic resonance (NMR) data suggest the inclusion of ABA in βCD via benzofuran ring. Isothermal titration calorimetry (ITC) experiments allowed to verify the formation of complex with a 1:1 stoichiometry, which was entropy driven. The dynamic light scattering and zeta potential data from inclusion compounds demonstrated changes in the size of the ABA/βCD HNP if compared with the ABA HNP. Finally, the results for biological assays demonstrate that the strategy to prepare the inclusion compound led to an increase in the larvicidal activity in relation to free ABA.

Plant-Derived Compounds as a Tool for the Control of Gastrointestinal Nematodes: Modulation of Abamectin Pharmacological Action by Carvone.

The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a significant increase in the intestinal concentrations was observed at 15 and 30 min after incubation with R-CNE. In the in vivo assay, no undesirable effects were observed after the oral administration of R-CNE. The coadministration of the natural compound prolonged ABM absorption in lambs. ABM T½ absorption was 1.57-fold longer (p < 0.05) in the coadministered group. Concentrations of R-CNE between 420 and 2,593 ng/mL were detected in the bloodstream between 1 and 48 h posttreatment. The in vivo efficacy of ABM against gastrointestinal nematodes increased from 94.9 to 99.8% in the presence of R-CNE, with the lower confidence interval limit being >90%. In vitro/in vivo pharmacoparasitological studies are relevant for the knowledge of the interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics. While ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and the molecular docking study showed a good interaction between ABM and P-gp, R-CNE does not appear to modulate this efflux protein. Therefore, the pharmacokinetic–pharmacodynamic effect of R-CNE on ABM should be attributed to its effect on membrane permeability. The development of pharmacology-based information is critical for the design of successful strategies for the parasite control.

The stress of abamectin toxicity reduced water quality, growth performance, immunity and antioxidant capacity of Oreochromis niloticus fish: Modulatory role of Simmondsia chinensis extract as a dietary supplement

The present study was conducted to investigate the toxic effect of abamectin (ABM) and to evaluate the modulatory role of heat treated jojoba leaves extract (JLE) as feed additive in Oreochromis niloticus (O. niloticus) fish. 300 Nile tilapia fingerlings were randomly distributed in to 5 equal groups (4 replicates each). The first group (control) was fed on basal diet. The second group (ABM) was fed on basal diet and exposed to 1/10 of the 96 h LC50 of ABM (20.73 μg/L). The third (ABM + JLE0.5), the fourth (ABM + JLE1) and the fifth (ABM + JLE2) groups were exposed to ABM and fed on diet supplemented with 0.5, 1 and 2 g JLE/kg, respectively. ABM altered the water quality parameters by increasing the total ammonia and reducing the dissolved oxygen while JLE reversed these effects. Apart from feed conversion, ABM decreased the growth parameters of exposed fish when compared to control. These values were modulated in JLE exposed groups in a concentration dependent manner. ABM increased ALT and AST levels while JLE1 and JLE0.5 restored their levels to the control values, respectively. ABM altered the lipid profile of exposed fish while JLE2 restored total cholesterol to normal value. Reduced glutathione content was decreased by ABM and was restored to normal by JLE2. The highest level of lipid peroxidation (MDA) was recorded in ABM and ABM + JLE0.5 groups while JLE1 and JLE2 decreased the MDA level. The total antioxidant capacity was decreased by ABM while the highest value was recoded in both control and JLE0.5 groups. The level of IgG, IgA and C3 were decreased by ABM while its level was restored to normal by using JLE. Exposure of fish to ABM resulted in a significant increase in the nitric oxide level. ABM group had lower moisture and higher crude lipids in the whole-fish body than the supplemented groups. It could be concluded that dietary supplementation of JLE can positively attenuate the toxic effects of ABM on growth, immunity, physiological and antioxidant parameters thereby improving the general health condition and decreasing the mortality of O. niloticus. Additionally, the heat treatment attempted on the leaves could be considered as an eco-friendly method for detoxification.

Comparative Acute Toxicity Assessment of Organophosphate and Avermectin Insecticides on a Freshwater Fish Oreochromis niloticus.

Oreochromis niloticus was exposed to 10.0ppb of organophosphate insecticide chlorpyrifos (CPF) and avermectin insecticides abamectin (ABM) and emamectin benzoate (EB) for 48 and 96h. RBC and Hb decreased in CPF- and ABM-exposed fish after 96-h. Plasma ALT, AST, cortisol, and glucose increased in 96-h CPF-, ABM- and EB-exposed fish, while plasma ions declined in 96-h CPF-exposed ones. Insecticides caused alterations in liver oxidative stress parameters. In fish exposed to CPF, CAT increased after 48-h whereas it decreased after 96-h. Also, CAT declined in 48- and 96-h ABM-exposed fish, whereas it elevated in 48-h EB-exposed ones. Insecticides caused decreases in SOD at 48- and 96-h and in GR after 96-h. GSH elevated in CPF-exposed fish after 48-h, while it decreased in all the tested insecticide exposures after 96-h. Malondialdehyde of fish exposed to insecticides for 96-h increased. Consequently, toxic effects of insecticides on O. niloticus were generally as CPF > ABM > EB.

Abamectin at environmentally-realistic concentrations cause oxidative stress and genotoxic damage in juvenile fish (Schizothorax prenanti)

Abamectin (ABM) has been extensively used in Chinese aquaculture systems for parasite control, but no information is available regarding its effects on the important freshwater commercial fish species Schizothorax prenanti. We performed an acute toxicity test to determine the effects of ABM on S. prenanti, and the 48- and 96-h median lethal concentration values were 33.32 and 15.98 μg/L, respectively. In a second test, animals were exposed to sublethal concentrations of ABM (0.5, 2 or 8 μg/L) for 8 days, and various cytological and biochemical parameters were measured. ABM caused DNA damage in hepatocytes, with significant increases in Olive Tail Moment values and 8-hydroxy-2'-deoxyguanosine levels. Hepatocytic apoptosis occurred following all treatments, and was accompanied by an increase in reactive oxygen species (ROS) generation and caspase activity in a dose- and time-dependent manner. In addition, there were significant decreases in glutathione peroxidase levels and superoxide dismutase and catalase activity and increases in malonaldehyde levels. ABM-induced hepatocytic apoptosis in S. prenanti was probably triggered by ROS generation following a cascade reaction of caspases in mitochondrial or death receptor pathways, which caused antioxidant inhibition, oxidative product accumulation, and DNA damage in the liver.

Construction and characterization of avermectin B2 solid nanodispersion

Poorly water-soluble pesticide compounds are difficult to be formulated as environmentally friendly formulations with high efficacy. For the conventional formulations, more than 50% of pesticides are lost during application due to the decomposition of active ingredient, dust drift and running off. Therefore, there is an urgent need to construct a novel formulation for improving the bioavailability of pesticides. The avermectin B2 solid nanodispersion was developed by self-emulsifying and solidification technology. The average particle size, surface tension and contact angle on cabbage leaves of the solid nanodispersion were 35.3 nm, 36.6 mN/m and 58°, respectively. The toxicities of the nanoformulation against diamondback moths and root-knot nematode were more than 1.7 times that of conventional emulsion in water and water dispersible granule. This investigation demonstrated that for foliage-applied pesticides, the formulation bioavailability had positive correlation with wettability which was negatively correlated with surface tension and contact angle. This study provides an easy and scalable technique to construct the effective and environmentally friendly nanoformulations. The toxicity improvement of the solid nanodispersion will significantly reduce dosage and environmental pollution of pesticide. The clarified relationship between formulation parameters and biological activity will contribute to the design and construction of novel pesticide formulations.

Characterization and optimization of abamectin-a powerful antiparasitic from a local Streptomyces avermitilis isolate.

Abamectin (ABA) constitutes a big commodity for pharmaceutical companies because it generates about one billion dollar annual sale. Avermectins (AVMs) and their naturally occurring analogues, milbemycins (MILs), meilingmycins (MEIs), ivermectin (IVE), abamectin (ABA), and nemadectin (NEM), represent one of the most developed antiparasitic agents. Abamectin is a mixture of avermectin B1a and avermectin B1b. The production of abamectin by Streptomyces avermitilis is a complicated process and separation of two fractions is quite difficult; commercial product contains more than 80% of Bla and less than 20% of B1b components. The main goal of the study was the identification and optimization of fermentation conditions to raise the production of abamectin from Egyptian S. avermitilis. The qualitative and quantitative analysis of avermectins was carried out by thin layer chromatography (TLC) and 6538 Q-TOF with Agilent 1290 UHPLC. The process of identification was carried out by using production medium containing 30g/L corn starch, and 0.725g/L CaCO3, pH7, 8% inoculum size and incubated at 32.5°C. The enhancement of the production of abamectin is a big challenge with commercial and industrial importance, as its output is insufficient for human consumption.

ROS accumulation contributes to abamectin-induced apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway in TM3 Leydig cells.

Abamectin (ABA) as one of the worldwide used compounds in agriculture has raised safety concerns on nontarget organism toxicity. However, the study of male reproductive system damage caused by ABA remains unclear. Our aim is to investigate the effect of ABA-induced cytotoxicity in TM3 Leydig cells and their underlying mechanisms. ABA inhibits TM3 cell viability and proliferation via cell cycle arrested in the G0/G1 phase. In addition, ABA-induced mitochondrial depolarization leads to an imbalance in Bcl-2 family expression, causing caspase-dependent apoptosis in TM3 cells. The increased ratio of cells expression LC3 protein and LC3-II to LC3-I indicated the activation of autophagy potentially. Further experiments revealed ABA treatment reduced phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) phosphorylation, and mammalian target of rapamycin (mTOR) phosphorylation. Pretreatment with a PI3K/AKT inhibitor, LY294002, mimicked the ABA-mediated effects on cytotoxicity. Pretreatment with a PI3K/AKT agonist, insulin-like growth factor-1, reversed the effects of ABA. ABA caused the accumulation of intracellular reactive oxygen species (ROS) by increased intensity of the ROS indicator. However, N-acetylcysteine as ROS scavengers inhibited ABA-induced apoptosis and autophagy and reversed these ABA-mediated effects on PI3K/AKT/mTOR pathway. On the basis of the above results, it is suggested that ABA exposure induces apoptosis and autophagy in TM3 cells by ROS accumulation to mediate PI3K/AKT/mTOR signaling pathway suppression.

Inhibition of TMEM16A Ca2+-activated Cl− channels by avermectins is essential for their anticancer effects

Transmembrane member 16A (TMEM16A) encoded Ca2+-activated Cl− channels were found to be involved in tumorigenesis. Previous studies suggest the effect of TMEM16A gene amplification on tumorigenic proliferation is exerted through its channel function. TMEM16A-specific and potent small molecule inhibitors have been proposed to potentially be useful for the treatment of cancer. Thus, we screened six analogues of avermectin for their inhibitory activities on TMEM16A mediated currents. A whole-cell patch technique was used to record the currents. The IC50 and Emax values for TMEM16A inhibition of five tested avermectins (avermectin B1, ivermectin, doramectin, selamectin, and moxidectin) were 0.15–1.32 μM and 65–87 %, respectively. In addition, these avermectins significantly inhibited endogenous TMEM16A mediated currents and thus, the proliferation, migration, inducing apoptosis of LA795 cancer cells. Eprinomectin (4”-(acetylamino)-4”-deoxy-avermectin B1) and two other important macrolides (erythromycin and azithromycin), which have minimal or no TMEM16A inhibitory effects, were used as negative control drugs. These drugs were found to have limited effects on the proliferation, migration, and apoptosis of LA795 cells. Finally, avermectin B1 and ivermectin dramatically inhibited the growth of xenograft tumors in mice. These data demonstrate that avermectins are novel TMEM16A inhibitors and are potentially useful in specific cancer therapies. These findings also provide a new opportunity to develop TMEM16A modulators.