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1.
Carbohydr Polym ; 345: 122553, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227095

ABSTRACT

The requirement to improve the efficiency of pesticide utilization has led to the development of sustainable and smart stimuli-responsive pesticide delivery systems. Herein, a novel avermectin nano/micro spheres (AVM@HPMC-Oxalate) with sensitive stimuli-response function target to the Lepidoptera pests midgut microenvironment (pH 8.0-9.5) was constructed using hydroxypropyl methylcellulose (HPMC) as the cost-effective and biodegradable material. The avermectin (AVM) loaded nano/micro sphere was achieved with high AVM loading capacity (up to 66.8 %). The simulated release experiment proved the rapid stimuli-responsive and pesticides release function in weak alkaline (pH 9) or cellulase environment, and the release kinetics were explained through release models and SEM characterization. Besides, the nano/micro sphere size made AVM@HPMC-Oxalate has higher foliar retention rate (1.6-2.1-fold higher than commercial formulation) which is beneficial for improving the utilization of pesticides. The in vivo bioassay proved that AVM@HPMC-Oxalate could achieve the long-term control of Plutella xylostella by extending UV shielding performance (9 fold higher than commercial formulation). After 3 h of irradiation, the mortality rate of P. xylostella treated by AVM@HPMC-Oxalate still up to 56.7 % ± 5.8 %. Moreover, AVM@HPMC-Oxalate was less toxic to non-target organisms, and the acute toxicity to zebrafish was reduced by 2-fold compared with AVM technical.


Subject(s)
Ivermectin , Moths , Ultraviolet Rays , Ivermectin/analogs & derivatives , Ivermectin/chemistry , Ivermectin/pharmacology , Ivermectin/toxicity , Animals , Moths/drug effects , Insecticides/chemistry , Insecticides/pharmacology , Insecticides/toxicity , Cellulose/chemistry , Cellulose/analogs & derivatives , Hypromellose Derivatives/chemistry , Hydrogen-Ion Concentration , Drug Liberation
2.
BMC Microbiol ; 24(1): 329, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39244577

ABSTRACT

BACKGROUND: Abamectin (ABA) is considered a powerful insecticidal and anthelmintic agent. It is an intracellular product of Streptomyces avermitilis; is synthesized through complicated pathways and can then be extracted from mycelial by methanol extraction. ABA serves as a biological control substance against the root-knot nematode Meloidogyne incognita. This investigation is intended to reach a new strain of S. avermitilis capable of producing ABA effectively. RESULTS: Among the sixty actinobacterial isolates, Streptomyces St.53 isolate was chosen for its superior nematicidal effectiveness. The mycelial-methanol extract of isolate St.53 exhibited a maximum in vitro mortality of 100% in one day. In the greenhouse experiment, the mycelial-methanol extract demonstrated, for the second-stage juveniles (J2s), 75.69% nematode reduction and 0.84 reproduction rate (Rr) while for the second-stage juveniles (J2s), the culture suspension demonstrated 75.38% nematode reduction and 0.80 reproduction rate (Rr). Molecular identification for St.53 was performed using 16 S rRNA gene analysis and recorded in NCBI Genbank as S. avermitilis MICNEMA2022 with accession number (OP108264.1). LC-MS was utilized to detect and identify abamectin in extracts while HPLC analysis was carried out for quantitative determination. Both abamectin B1a and abamectin B1b were produced and detected at retention times of 4.572 and 3.890 min respectively. CONCLUSION: Streptomyces avermitilis MICNEMA2022 proved to be an effective source for producing abamectin as a biorational agent for integrated nematode management.


Subject(s)
Ivermectin , Streptomyces , Tylenchoidea , Streptomyces/genetics , Streptomyces/metabolism , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Ivermectin/metabolism , Animals , Tylenchoidea/drug effects , RNA, Ribosomal, 16S/genetics , Anthelmintics/pharmacology , Phylogeny , Antinematodal Agents/pharmacology , Antinematodal Agents/metabolism , Plant Diseases/parasitology , Plant Diseases/microbiology , Plant Diseases/prevention & control , Biological Control Agents/pharmacology
3.
Environ Monit Assess ; 196(10): 925, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264478

ABSTRACT

This is the first report on high pesticide tolerance displayed by the microbiota isolated from the sediments of two high-altitude lakes, located in the Singalila National Park, Singalila Ridge of the Himalayas. Given the remote location of these lakes, direct exposure to chemical pesticides is highly unlikely. However, the high tolerance to commonly used pesticides exhibited, i.e. up to 250 mg/ml, suggests repeated exposure and contamination of the lakes. Microbial growth in the presence of varying concentrations of the pesticides, namely, emamectin benzoate, thiamethoxam, quinalphos, deltamethrin, spiromesifen, flubendiamide, monocrotophos, fipronil, fenazaquin and phorate, was tested. Results showed resistance to all pesticides except fenazaquin and fipronil, up to 250 mg/ml. For the latter two, tolerance was displayed up to a concentration of 40 mg/ml. Tolerance may potentially result from the transport and deposition of pesticides from nearby locations, particularly the tea plantations of Darjeeling and Eastern Nepal. This may create great ecological risks as these lakes are an important water source for endemic wildlife of this protected area. They also hold great significance to the religious sentiment of the local tribes who worship these lakes as sacred. The study highlights the need for monitoring pesticide contamination in such pristine high-altitude environments and the mechanisms of long-range pollutant transport.


Subject(s)
Altitude , Environmental Monitoring , Lakes , Pesticides , Water Pollutants, Chemical , Lakes/microbiology , Lakes/chemistry , Pesticides/analysis , Water Pollutants, Chemical/analysis , Nepal , Nitriles/toxicity , Microbiota/drug effects , Pyrethrins , Himalayas , Ivermectin/analogs & derivatives
4.
Cancer Chemother Pharmacol ; 94(4): 599-613, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39235611

ABSTRACT

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Conventional chemotherapy remains unsatisfactory due to drug toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatments for advanced osteosarcoma. In the current study, we focused on evaluating the anticancer efficacy of avermectin B1, a novel avermectin analog, against osteosarcoma cells. METHODS: The half-inhibitory concentration of avermectin B1 was calculated in three osteosarcoma cell lines. Then, functional experiments were conducted to evaluate the effects of avermectin B1 on cell proliferation, the cell cycle, apoptosis and autophagy. Moreover, the AMPK/ULK1 signaling pathway was detected by Western blot assay. Finally, the in vivo effect of avermectin B1 on tumor growth and metastasis was investigated using the xenograft mouse model. To examine the role of the AMPK/ULK1 pathway, an AMPK-specific inhibitor (dorsomorphin) was used in combination with avermectin B1. RESULTS: Avermectin B1 inhibited the proliferation of osteosarcoma cells in a dose-dependent manner based on CCK8 and colony formation assays. Then, it was found to inhibit migration and invasion by wound healing assay and cell migration and invasion assay. In addition, avermectin B1 induced osteosarcoma cell apoptosis and autophagy. In vivo, avermectin B1 effectively inhibited osteosarcoma cell growth and pulmonary metastasis. Mechanistically, avermectin B1 activated the AMPK/ULK1 pathway to exert antitumor activity in vitro and in vivo. Dorsomorphin significantly attenuated the Avermectin B1-induced antitumor activities. CONCLUSION: Our study suggests that avermectin B1 is a potential agent to treat osteosarcoma cells through the AMPK/ULK1 signaling pathway.


Subject(s)
AMP-Activated Protein Kinases , Autophagy , Bone Neoplasms , Ivermectin , Osteosarcoma , Signal Transduction , Animals , Humans , Mice , AMP-Activated Protein Kinases/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Autophagy-Related Protein-1 Homolog/metabolism , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Intracellular Signaling Peptides and Proteins/metabolism , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Mice, Inbred BALB C , Mice, Nude , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
5.
Sci Rep ; 14(1): 22565, 2024 09 29.
Article in English | MEDLINE | ID: mdl-39343793

ABSTRACT

The red palm weevil (RPW), Rhynchophorus ferrugineus Olivier, is a devastating insect-pest of 29 plants including date palm. It feeds inside the tree bark thus it is difficult to manage using insecticides. Only a few insecticides have been found effective against RPW. Among these insecticide, emamectin benzoate (EMB) is widely used. This insecticide can pose threat human and environmental health as it is used in the form of tree injection. Thus, keeping in view its possible, its sublethal effect on RPW was studied using Age-stage, two sex life table. Life table parameters of the progeny of exposed larvae to LC10, LC25, and LC50 of EMB were computed. Statistically higher fecundity (161.12 per female) was observed in control treatment, while less fecundity was observed in LC50 treatment. Significantly higher values for intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (Ro) (0.0376, 1.0383, and 67.13 per day, respectively) were recorded for the control treatment. Contrarily, lower values for r, Ro, and λ i.e. 0.0318, 23.82, and 1.0324 per day, respectively were recorded in the LC50 treatment. Decreased population parameters suggest that EMB can be successfully used in for the management of RPW.


Subject(s)
Insecticides , Ivermectin , Life Tables , Weevils , Animals , Weevils/drug effects , Weevils/growth & development , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Ivermectin/toxicity , Insecticides/pharmacology , Insecticides/toxicity , Female , Male , Larva/drug effects , Fertility/drug effects , Reproduction/drug effects
6.
Braz J Biol ; 84: e286883, 2024.
Article in English | MEDLINE | ID: mdl-39319931

ABSTRACT

Date palm trees, their cultivation and harvesting have become challenging due to infestations caused by some specific mites including Oligonychus afrasiaticus (McGregor) (Tetranychidae). Current research has been carried out to investigate the efficiency of nine pesticides against eggs and date palm mite, Oligonychus afrasiaticus against nine pesticides. Side effects of the nine pesticides were also examined on predatory mite, Amblyseius swirskii Athias-Henriot (Phytoseiidae). Mites and their eggs were treated with the recommended dosage of nine pesticides namely, Bifenazate 24%, Bifenthrin 10%, Matrine 0.6%, Imidacloprid 37% + Abamectin 3%, Sulphur 99.5%, Micronized Sulphur 80%, Mineral oil 95%, Pyrethrin 1.5% and Hexythiazox 10%, while they were present in their natural environment on the date palm trees in the experimental fields. Highest mortality of 91.16% was observed when O. afrasiaticus was treated with Bifenazate (24%) followed by 87.31%, 85.20%, 72.06%, 71.34%, 65.35%, 64.14%, 61.06% and 24.25% in case of Bifenthrin 10%, Matrine 0.6%, Imidacloprid 37% + Abamectin 3%, Sulphur 99.5%, Micronized Sulphur 80%, Mineral oil 95%, Pyrethrin 1.5%, and Hexythiazox 10%, respectively. A minimum hatching of 25.74% was observed when eggs of O. afrasiaticus were treated with Hexythiazox 10% and the highest success of hatching (99.07%) was seen when treatment was given with Imidacloprid 37% + Abamectin 3%. When same trials with same nine pesticides were performed on predatory mite; Amblyseius swirskii, the highest mortality in terms of percentage reduction (75.63%) was observed with Bifenthrin and the lowest (14.69%) with Matrine. Nine pesticides used in this study have distinct toxicity against targeted mite, their eggs and the predatory mite. A two steps control strategy is recommended for this treatment. First spray Hexythiazox at the egg laying stage and then at the moving stage of mites by using Matrine which is toxic to mites but negligibly toxic to predatory mites. Further studies are recommended to evaluate varied actions of the pesticide against eggs, phytophagous mites, and predatory mites.


Subject(s)
Acaricides , Mites , Neonicotinoids , Animals , Mites/drug effects , Phoeniceae , Tetranychidae/drug effects , Pyrethrins , Alkaloids/pharmacology , Nitro Compounds , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Matrines , Quinolizines/pharmacology
7.
Ecotoxicol Environ Saf ; 284: 116964, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39260218

ABSTRACT

Avermectin (AVM), a compound derived from the fermentation of Avermectin Streptomyces, has insecticidal, acaricidal, and nematicidal properties. Widely employed in agriculture, it serves as an effective and broad-spectrum insecticide for pest control. Although the toxicity of AVM at low doses may not be readily apparent, prolonged and extensive exposure can result in poisoning. To investigate the toxic effects of AVM on the body, this study established rat models of AVM poisoning with both low and high concentrations of the compound. Fifteen male rats were randomly assigned to one of three groups (n=5 per group): a control group, a low-concentration group, and a high-concentration group. The low-concentration group was administered an oral dose of 2 mg/kg AVM once daily for a duration of seven days, while the high-concentration group received an oral dose of 10 mg/kg AVM once daily for the same period. This study examined the impact of AVM on liver function and gut microbiota in rats using weight monitoring, liver function indicator detection, liver metabolomics sequencing, colon barrier function testing, and gut microbiota sequencing. The findings of this study demonstrated that exposure to 2 or 10 mg/kg AVM for seven days can lead to a notable decrease in rat weight, as well as induce liver dysfunction and metabolic disturbances. Additionally, AVM exposure can disrupt the composition of the intestinal microbiota and impair the integrity of the colon mucosal barrier, causing downregulation of Occludin expression and upregulation of inflammation-related protein expression levels such as IL-1ß, Myd88, and TLR4. Furthermore, bioinformatics analysis revealed a significant association between liver dysfunction and dysbiosis of the gut microbiota. These findings have implications for the agricultural use of AVM and its potential contribution to environmental pollution. Consequently, individuals involved in AVM usage should prioritize safety precautions and monitor liver function.


Subject(s)
Colon , Gastrointestinal Microbiome , Insecticides , Ivermectin , Liver , Animals , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Male , Gastrointestinal Microbiome/drug effects , Liver/drug effects , Liver/pathology , Rats , Colon/drug effects , Colon/pathology , Insecticides/toxicity , Rats, Sprague-Dawley
8.
ACS Appl Mater Interfaces ; 16(38): 51318-51332, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39276181

ABSTRACT

The development of intelligent multifunctional nanopesticides featuring enhanced foliage affinity and hierarchical target release is increasingly pivotal in modern agriculture. In this study, a novel cationic amphiphilic comb-shaped polymer, termed PEI-TA, was prepared via a one-step Michael addition between low-molecular-weight biodegradable polyethylenimine (PEI) and tetradecyl acrylate (TA), followed by neutralization with acetic acid. Using the emulsifier PEI-TA, a positively charged avermectin (AVM) nanoemulsion was prepared via a phase inversion emulsification process. Under optimal formulation, the obtained AVM nanoemulsion (defined as AVM@PEI-TA) demonstrated exceptional properties, including small size (as low as 67.6 nm), high encapsulation efficiency (up to 87.96%), and high stability toward shearing, storage, dilution, and UV irradiation. The emulsifier endowed AVM@PEI-TA with a pronounced thixotropy, so that the droplets exhibited no splash and bounce when they were sprayed on the cabbage leaf. Owing to the electrostatic attraction between the emulsifier and the leaf, AVM@PEI-TA showed improved leaf adhesion, better deposition, and higher washing resistance in contrast to both its negatively charged counterpart and AVM emulsifiable concentrate (AVM-EC). Compared to the large-sized particles, the small-sized particles of the AVM nanoemulsion more effectively traveled long distances through the vascular system of veins after entering the leaf apoplast. Moreover, the nanoparticles lost stability when exposed to multidimensional stimuli, including pH, temperature, esterase, and ursolic acid individually or simultaneously, thereby promoting the release of AVM. The release mechanisms were discussed for understanding the important role of the emulsifier in nanopesticides.


Subject(s)
Emulsifying Agents , Emulsions , Ivermectin , Ivermectin/analogs & derivatives , Ivermectin/chemistry , Ivermectin/pharmacology , Emulsions/chemistry , Emulsifying Agents/chemistry , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Plant Leaves/chemistry , Polyethyleneimine/chemistry , Nanoparticles/chemistry , Brassica/chemistry , Drug Liberation , Particle Size , Acrylates/chemistry , Cations/chemistry , Polymers/chemistry
9.
Braz J Biol ; 84: e282436, 2024.
Article in English | MEDLINE | ID: mdl-39194021

ABSTRACT

The present study has been conducted to evaluate the effect of two sprays of seven pesticides at recommended dose on citrus brown mite, Eutetranychus orientalis and the side effects on their predatory mites, Euseius scutalis, Amblyseius swirskii, Phytoseiulus persimilis (Acari: Phytoseiidae) under field conditions at 2022 & 2023 seasons. The obtained results show that, all tested pesticides achieved high reduction % of E. orientalis ranged between (82.1-90.0%) and (81.6-87.1%) after the 1st and 2nd sprays of 2022 season, where it ranged between (84.9- 88.7%) and ( 79.7- 88.7%) after 1st and 2nd sprays of 2023 season. Abamectin recorded the highest reduction % against the citrus brown mite, whereas Congest pesticide recorded the lowest reduction % after the two sprays along 2022 & 2023 seasons. As for the side effects of tested pesticides on associated predatory mites, all pesticides were safely for E. scutalis numbers recording decrease % between (18.4-28.6%) and (16.2 -26.1%) after the 1st and 2nd spray at 2022 season , where it ranged between (15.3- 29.1%) and (19.6-32.0%) after the 1st and 2nd sprays of 2023 season. On contrary, imidacloprid was unsafely for E. scutalis numbers recording the highest mean decrease % after 1st and 2nd sprays during the two seasons. Also, all tested pesticides were safely for A. swirskii numbers, after the 1st and 2nd sprays of the two seasons recording decrease (from 10.9 to 28.1%) & (24.4 to 31.4%) for the 2022 season, and (19-38.9%) & (18.7-39.4%) at 2023 season. On contrary, imidacloprid was unsafely for A. swirskii numbers recorded the highest decrease % after 1st and 2nd sprays during the two seasons. As for, Ph. Persimilis numbers, all tested pesticides were safely, where it recorded low decrease % ranged between (17-33.8%) & (20.4-34.8%) after the 1st and 2nd sprays of 2022 season, and (24.3-39%) & (20.2-28.9%) after the 1st and 2nd sprays of 2023 season. On the other side, imidacloprid was unsafely for Ph. persimilis numbers recording the highest decrease % after the 1st and 2nd sprays during the two seasons. The present study proved that all tested pesticides were high effective against E. orientalis and appeared to be safely and selective for associated predatory mites except imidacloprid which was very harmful for all tested predatory mites, and it could be concluded that the tested pesticides, Fenpyroximate, Hexythiazox , Congest , Spirodiclofen, Abamectin, and Chlorfenapyr could be used in the Integrated Pest Management (IPM) programs for E. orientalis at citrus orchards.


Subject(s)
Citrus , Neonicotinoids , Predatory Behavior , Seasons , Tetranychidae , Animals , Predatory Behavior/drug effects , Tetranychidae/drug effects , Acaricides , Mites/drug effects , Mites/classification , Nitro Compounds , Ivermectin/analogs & derivatives , Pyrethrins , Pesticides/pharmacology
10.
Vet Parasitol ; 331: 110271, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39089177

ABSTRACT

The metastrongyloids Aelurostrongylus abstrusus and Troglostrongylus brevior are primary causes of feline clinical respiratory disease. The present field trial evaluated the clinical efficacy of a spot-on formulation containing eprinomectin, esafoxolaner and praziquantel (NexGard® Combo) administered per label recommendations to cats affected with aelurostrongylosis and/or troglostrongylosis. Overall, 36 naturally infected cats were randomly assigned to Group 1 (G1) or Group 2 (G2) of 18 cats each. The two groups included 6 cats with A. abstrusus, T. brevior and mixed infection, each. All cats completed the study. Cats in G1 were treated on study Days (SDs) 0 and 28±2. Cats in G2 served as negative control until SD 56±2 and were then treated on SD 56±2 and 84±2. On SD 0/-7, 28±2 and SD 56±2 all cats were subjected to parasitological (quali-quantitative Baermann) and clinical examinations (physical exams and thoracic X-rays). Hematology and biochemistry analyses were performed on SD 0/-7 and SD 56±2. On SD 84±2 quali-quantitative Baermann, clinical examination and thorax radiography were performed on all G2 cats and on two G1 cats that still had radiographic alterations on SD 56±2. On SD 112±2 all G2 cats were subjected to parasitological and clinical evaluations and one cat from G1 that still had radiographic signs at SD 84±2 was clinically and radiographically evaluated. Efficacy criteria were the reduction of larval shedding in faeces and the clinical response in terms of pathological and radiographic scores after treatment compared to the baseline. An efficacy of 100 % based on LPG reduction was recorded after one (20/24 cats) or two (all 24 cats) treatments in cats with single infection by A. abstrusus or T. brevior. For cats with mixed infections, larval shedding was stopped after one (11/12 cats) or two (all 12 cats) treatments. Statistically significant clinical and radiographic improvement was evident in all study cats after 2 treatments. The present data show that two monthly treatments with NexGard® Combo stopped larval shedding and led to a significant clinical recovery and a complete resolution of radiographic abnormalities in cats infected with A. abstrusus and/or T. brevior.


Subject(s)
Cat Diseases , Ivermectin , Metastrongyloidea , Praziquantel , Strongylida Infections , Animals , Cats , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Cat Diseases/drug therapy , Cat Diseases/parasitology , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Ivermectin/analogs & derivatives , Strongylida Infections/drug therapy , Strongylida Infections/veterinary , Strongylida Infections/parasitology , Metastrongyloidea/drug effects , Male , Female , Drug Combinations , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Feces/parasitology , Treatment Outcome
11.
J Hazard Mater ; 477: 135376, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39111175

ABSTRACT

Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.


Subject(s)
Apoptosis , Ivermectin , Larva , Mitochondria , Receptors, Notch , Signal Transduction , Vascular Endothelial Growth Factor A , Zebrafish , Animals , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Apoptosis/drug effects , Signal Transduction/drug effects , Larva/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Receptors, Notch/metabolism , Insecticides/toxicity , Blood Vessels/drug effects
12.
Ecotoxicol Environ Saf ; 284: 116917, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39182280

ABSTRACT

The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), poses a significant threat to food security, necessitating effective management strategies. While chemical control remains a primary approach, understanding the toxicity and detoxification mechanisms of different insecticides is crucial. In this study, we conducted leaf-dipping bioassays to assess the toxicity of quinalphos and beta-cypermethrin·emamectin benzoate (ß-cyp·EMB) on S. frugiperda larvae. Additionally, we assessed the response of alterations in CarE, GST, MFO, and AChE activities to sublethal concentrations of these insecticides over various treatment durations. Results indicated that ß-cyp·EMB exhibited higher toxicity than quinalphos in S. frugiperda. Interestingly, the highest activities of GST, CarE, MFO, and AChE were observed at 6 h exposure to LC10 and LC25 of ß-cyp·EMB, surpassing equivalent sublethal concentrations of quinalphos. Subsequently, GST and CarE activities exposure to ß-cyp·EMB steadily decreased, while MFO and AChE activities exposure to both insecticides was initially decreased then increased. Conversely, two sublethal concentrations of quinalphos notably enhanced GST activity across all exposure durations, with significantly higher than ß-cyp·EMB at 12-48 h. Similarly, CarE activity was also increased at various durations. Our research has exhibited significant alterations in enzyme activities exposure to both concentration and duration. Furthermore, Pearson correlation analysis showed significant correlations among these enzyme activities at different treatment durations. These findings contribute to a better understanding of detoxification mechanisms across different insecticides, providing valuable insights for the rational management of S. frugiperda populations.


Subject(s)
Inactivation, Metabolic , Insecticides , Ivermectin , Larva , Pyrethrins , Spodoptera , Animals , Insecticides/toxicity , Spodoptera/drug effects , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Larva/drug effects , Pyrethrins/toxicity , Acetylcholinesterase/metabolism , Glutathione Transferase/metabolism
13.
Vet Res Commun ; 48(5): 3139-3155, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39106005

ABSTRACT

Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175 µg/kg 3H-IVM (8.6 µCi/mg IVM) with or without co-administration of 480 µg/kg CsA into the caudal vasculature. Fish were sacrificed at various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) for organ and tissue sampling (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad, and fat) which were analyzed for IVM-derived radioactivity. The IVM concentration decreased over time in blood, liver, kidney, and gill, while concentrations in other tissues remained constant. The highest maximum IVM concentration (Cmax) was found in kidney, followed by liver; the lowest Cmax was found in eye, followed by brain and adipose tissue. The highest % of the administered dose was found in the blood 15 min post-IVM administration, followed by the intestine at 60 min post-IVM administration. P-gp inhibition by CsA did not significantly affect calculated TK parameters (AUC [7.33 ± 0.73 - 11.5 ± 2.5 mg•h/kg], mean residence time [84.7 ± 21 - 125 ± 55 h], T1/2 [58.7 ± 15 - 86.8 ± 38 h], clearance rate [0.0152 ± 0.0033 - 0.0239 ± 0.0024 L/kg•h], or volume of distribution [1.91 ± 0.47 - 2.02 ± 0.33 L/kg]), but resulted in small but significant changes in the % administered dose found in blood and medulla. These results suggest that P-gp plays a limited role in overall IVM TK, and that its role in xenobiotic protection may be much less robust in fish than it is in mammals.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Cyclosporine , Ivermectin , Oncorhynchus mykiss , Animals , Oncorhynchus mykiss/metabolism , Ivermectin/analogs & derivatives , Ivermectin/pharmacokinetics , Ivermectin/toxicity , Ivermectin/blood , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cyclosporine/pharmacokinetics , Toxicokinetics , Antiparasitic Agents/pharmacokinetics , Tissue Distribution
14.
Parasite ; 31: 44, 2024.
Article in English | MEDLINE | ID: mdl-39109981

ABSTRACT

Amblyomma maculatum, the Gulf Coast tick, infests a wide range of vertebrate species including livestock, dogs, cats, and humans. It is a species of significant veterinary and public health importance, especially as a vector of diseases, for instance American canine hepatozoonosis or tidewater spotted fever. An experimental study was conducted to evaluate the efficacy of NexGard® Combo, a topical endectoparasiticide product for cats combining eprinomectin, praziquantel and esafoxolaner, against induced infestations of A. maculatum in cats. This Good Clinical Practice (GCP) study used a randomized, negative controlled, masked design. Ten cats were allocated to an untreated group and ten to a treated group, dosed once on Day 0 at the minimum label dose. On Days -2, 7, 14, 21, 28, 35, and 42, cats were infested with ~50 unfed adult A. maculatum. On Days 3, 10, 17, 24, 31, 38, and 45, i.e., 72 h after treatment and subsequent infestations, ticks were removed, counted and the numbers of live attached tick in each group were used for efficacy calculations. At each time-point, all untreated cats were adequately infested, demonstrating a vigorous tick population and an adequate study model. The curative efficacy after a single application against existing tick infestation, 72 h after treatment, was 98.7%. The preventive efficacy, 72 h after weekly infestations, over the following five weeks ranged from 93.8% to 99.4%.


Title: Efficacité d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les infestations par Amblyomma maculatum chez le chat. Abstract: Amblyomma maculatum, la tique de la Gulf Coast, infeste un large éventail d'espèces de vertébrés, notamment le bétail, les chiens, les chats et les humains. Il s'agit d'une espèce d'importance significative en médecine vétérinaire et en santé publique, notamment en tant que vecteur de maladies, par exemple l'hépatozoonose canine américaine ou la fièvre pourprée des marées. Une étude expérimentale a été menée pour évaluer l'efficacité de NexGard® Combo, un produit endectoparasiticide topique pour chats associant éprinomectine, praziquantel et esafoxolaner, contre les infestations par A. maculatum provoquées chez le chat. Cette étude de bonnes pratiques cliniques (BPC) a utilisé une conception randomisée, contrôlée négativement et masquée. Dix chats ont été répartis dans un groupe non traité et dix chats dans un groupe traité, traités une fois au jour 0 à la dose minimale indiquée sur l'étiquette. Aux jours −2, 7, 14, 21, 28, 35 et 42, les chats ont été infestés par environ 50 A. maculatum adultes non nourris. Les jours 3, 10, 17, 24, 31, 38 et 45, c'est-à-dire 72 heures après le traitement et les infestations ultérieures, les tiques ont été retirées, comptées et le nombre de tiques vivantes attachées dans chaque groupe a été utilisé pour les calculs d'efficacité. À chaque instant, tous les chats non traités étaient correctement infestés, démontrant une population de tiques vigoureuse et un modèle d'étude adéquat. L'efficacité curative après une seule application contre une infestation de tiques existante, 72 heures après le traitement, était de 98,7%. L'efficacité préventive, 72 heures après les infestations hebdomadaires, au cours des cinq semaines suivantes, variait entre 93,8% et 99,4%.


Subject(s)
Amblyomma , Cat Diseases , Ivermectin , Praziquantel , Tick Infestations , Animals , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Cats , Cat Diseases/drug therapy , Cat Diseases/parasitology , Tick Infestations/veterinary , Tick Infestations/drug therapy , Tick Infestations/parasitology , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Ivermectin/analogs & derivatives , Female , Male , Administration, Topical , Drug Combinations , Treatment Outcome , Acaricides/administration & dosage , Acaricides/therapeutic use
15.
Arch Insect Biochem Physiol ; 116(4): e22144, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39166339

ABSTRACT

Tenvermectin B (TVM-B) and five TVM-B analogs were produced by fermentation of a genetically engineered strain Streptomyces avermitilis HU02, and TVM-B is being developed as a new insecticide. Through 11 generations of resistance selection against TVM-B in the diamondback moth, Plutella xylostella, the median lethal concentration (LC50) was increased from 14.84 to 1213.73 mg L-1. The resistance to TVM-B in P. xylostella developed fast and its realized heritability was high (h2 = 0.2901 (F7), h2 = 0.4070 (F11)). However, the relative fitness was 0.6916 suggesting a fitness cost in the resistant strains. The fitness cost was partially explained by the upregulation of the detoxification enzyme activity by 2.15 folds in carboxylate esterase (CarE) and the gene expressions of ATP-binding cassette transporter gene (ABCC2) and the alpha subunit of the glutamate-gated chloride channel (GluCl) by 1.70- and 2.32 folds, respectively. The resistance was also explained by two points of mutations at the alpha subunit of the glutamate-gated chloride channel in the P. xylostella (PxGluClα) subunit in F11. However, there was little change in the binding affinity. These results provided helpful information for the mechanism study of TVM-B resistance and will be conducive to designing rational resistance management strategies in P. xylostella.


Subject(s)
Insecticide Resistance , Insecticides , Ivermectin , Moths , Animals , Moths/genetics , Moths/growth & development , Moths/metabolism , Moths/drug effects , Moths/enzymology , Insecticide Resistance/genetics , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Insecticides/pharmacology , Genetic Fitness , Chloride Channels/genetics , Chloride Channels/metabolism , Larva/growth & development , Larva/genetics , Larva/metabolism , Insect Proteins/genetics , Insect Proteins/metabolism
16.
Biochem Biophys Res Commun ; 732: 150404, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39033553

ABSTRACT

The avermectin derivative doramectin is widely used clinically as an antiparasitic drug and, in addition, doramectin may have a modulatory role in obesity. Adipose tissue macrophage recruitment and polarization play an important role in obesity-induced inflammation and insulin resistance. The aim of this study was to investigate the effects of doramectin on high-fat diet-induced inflammation and macrophage polarization in white adipose tissue of epididymis of obese mice. We found that compared with high-fat diet-fed obese mice, doramectin treatment resulted in a significant decrease in body weight and lipid levels, improved insulin resistance, an increase in the proportion of M2-type macrophages and a decrease in the proportion of M1-type macrophages in the epididymal white adipose tissues, as well as a decrease in the infiltration of inflammatory cells in the adipose tissues. Thus, doramectin can ameliorate high-fat diet-induced obesity and adipose inflammation by affecting macrophage polarization in white adipose tissue.


Subject(s)
Diet, High-Fat , Inflammation , Insulin Resistance , Ivermectin , Macrophages , Mice, Inbred C57BL , Obesity , Animals , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology , Male , Inflammation/drug therapy , Inflammation/pathology , Inflammation/metabolism , Mice , Diet, High-Fat/adverse effects , Macrophages/drug effects , Macrophages/metabolism , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Adipose Tissue, White/pathology , Mice, Obese
17.
Pestic Biochem Physiol ; 203: 106012, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39084804

ABSTRACT

Liriomyza trifolii, an invasive pest, poses a substantial threat to horticultural and vegetable plants. It spreads rapidly, especially in hot weather, leading to large-scale outbreaks with strong thermotolerance and insecticide resistance. In this study, mortality and LtCYP4g1 expression in L. trifolii were evaluated after thermal and insecticides exposure. Furthermore, functional verification of LtCYP4g1 was conducted through RNA interference and bacterial survival assays in Escherichia coli containing recombinant LtCYP4g1 protein. Results indicated that a short time exposure to high temperature incresed insecticide tolerance of L. trifolii, attributed to decreased mortality and induced LtCYP4g1 expression; LtCYP4g1 was involved in stimulating synthesis of cuticular hydrocarbons (CHCs) and elevating epicuticle lipid content and thickness, and E. coli cells overexpressing LtCYP4g1 exhibited significant tolerance to thermal and insecticide stress. In general, P450-mediated tolerance of L. trifolii was enhanced by high temperature, with LtCYP4g1 playing a role in promoting biosynthesis of CHCs for thickening epidermal lipid barrier and reducing cuticular penetration. This study provides a framework for delving into the function of CYP450s in insecticide detoxification and illustrates the role of global warming in driving the evolution of L. trifolii.


Subject(s)
Cytochrome P-450 Enzyme System , Insecticides , Ivermectin , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Animals , Insecticides/pharmacology , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Insecticide Resistance/genetics , Hydrocarbons/metabolism , Hot Temperature , Escherichia coli/drug effects , Escherichia coli/genetics , Coleoptera/drug effects , Coleoptera/genetics , Insect Proteins/genetics , Insect Proteins/metabolism
18.
Vet Res Commun ; 48(5): 3365-3369, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39012470

ABSTRACT

Lamanema chavezi is an entero-hepatic strongylid parasite specific to South American camelids. It has been reported only on few occasions outside South America. Due to its hepatic migration, it can cause extensive liver damage, leading to granulomatous and fibrotic hepatitis and manifesting with lethargy, anorexia, and even death. We are reporting the second case of L. chavezi infection in Europe and the first in Switzerland. The patient was a three-year old neutered male llama (Lama glama). Clinical examination revealed bloody mucous discharge from the anus. Fecal sedimentation/flotation revealed strongylid eggs consistent with L. chavezi, which were molecularly confirmed by a PCR targeting the ITS2 plus 5.8S and 28S rDNA flanking regions and amplicon sequencing. Eighteen weeks after administration of a single dose of eprinomectin (0.2 mg/kg i.m.), no further L. chavezi eggs were detected in the feces. The source of infection could not be traced back. The entire herd consisted of llamas bred in Switzerland. L. chavezi has been rarely reported outside South America, but its potential for pathogenicity and establishment should not be underestimated. Fecal sedimentation/flotation techniques should be routinely performed to ensure early detection of the parasite.


Subject(s)
Camelids, New World , Animals , Camelids, New World/parasitology , Male , Switzerland , Strongylida Infections/veterinary , Strongylida Infections/diagnosis , Strongylida Infections/parasitology , Feces/parasitology , Ivermectin/therapeutic use , Ivermectin/analogs & derivatives , Anthelmintics/therapeutic use
19.
Nat Commun ; 15(1): 5687, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38971862

ABSTRACT

Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.


Subject(s)
CRISPR-Cas Systems , Cytosine , Gene Editing , Polyketide Synthases , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Gene Editing/methods , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Cytosine/metabolism , Ivermectin/analogs & derivatives , Ivermectin/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Oligomycins
20.
Drugs R D ; 24(2): 331-340, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39034337

ABSTRACT

BACKGROUND AND OBJECTIVE: Trichuriasis caused by the human whipworm Trichuris trichiura poses a significant public health concern. Albendazole-ivermectin co-medication is currently the most effective treatment. Studies conducted in Tanzania and Côte d'Ivoire unveiled differences in efficacy for albendazole-ivermectin combination therapy in both countries. A pharmacometrics approach was used to assess co-medication and study population effects on the pharmacokinetics of the two main metabolites of albendazole. An exploratory exposure-efficacy analysis was also carried out to investigate relationships between exposure measures and the egg reduction rate. METHODS: Pharmacokinetic data from studies in Tanzania and Côte d'Ivoire in adolescents (aged 12-19 years) were included in the pharmacometric analysis. Participants received a single dose of either albendazole 400 mg alone or in combination with ivermectin 200 µg/kg. A pharmacometric analysis was performed to investigate the potential effects of the study population and co-administered ivermectin on the apparent clearance of the metabolites of albendazole. Non-linear mixed-effects modeling was conducted with MonolixSuite 2023R1. The pharmacokinetic exposure measures derived from simulations with individual model parameters were used in the exploratory-exposure response analysis. RESULTS: Pharmacokinetic profiles were best described by a two-compartment model for albendazole sulfoxide and a one-compartment model for albendazole sulfone, with a transit compartment and linear elimination. While no co-medication effect was found, apparent clearance of albendazole sulfoxide (albendazole sulfone) in the Tanzanian study population was 75% (46%) higher than that in the Côte d'Ivoire study population. Exposure-efficacy response analyses indicated that peak concentration and the time-above-exposure threshold were associated with the egg reduction rate. CONCLUSIONS: Study population but not co-administered ivermectin showed an effect on apparent clearance of albendazole sulfoxide and albendazole sulfone. Polymorphisms in drug-metabolizing enzymes and host-parasite interaction may explain this result. Difference in drug exposure did not explain the disparate efficacy responses in Tanzania and Côte d'Ivoire. Peak concentration and time-above-threshold were exposure measures associated with the egg reduction rate. Further studies evaluating genetic and resistance patterns in various regions in Africa are warranted.


Subject(s)
Albendazole , Drug Therapy, Combination , Ivermectin , Trichuriasis , Trichuris , Albendazole/pharmacokinetics , Albendazole/analogs & derivatives , Albendazole/administration & dosage , Albendazole/pharmacology , Albendazole/therapeutic use , Humans , Cote d'Ivoire , Adolescent , Tanzania , Child , Young Adult , Trichuris/drug effects , Male , Trichuriasis/drug therapy , Female , Animals , Ivermectin/pharmacokinetics , Ivermectin/therapeutic use , Ivermectin/pharmacology , Ivermectin/analogs & derivatives , Anthelmintics/pharmacokinetics , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage
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