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1.
Vet Parasitol ; 296: 109498, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34139615

ABSTRACT

In our previous studies, we found that as the active gradients of Adonis coerulea, cardenolides and cardiac glycosides presented toxicity against mites by inhibiting Na+-K+-ATPase. In this paper, after evaluating the acaricidal activity of the commercial cardiac aglycones/glycosides, serials of novel strophanthidin derivatives were designed and synthesized with an efficient and simple route under mild conditions, and their toxicity against mites, the cytotoxicity and inhibitory effect on Na+-K+-ATP enzyme in PC12 cells were investigated. Results showed among of all compounds, including 9 commercial agent and 32 synthesized strophanthidin derivatives, QXG-1 presented the strongest toxicity against mites with the LC50 value of 320.0 µg/mL. C-19 group of strophanthidin substituted with glycinemethylester would increase the toxicity against mites, and the hydroxyl group at C-5 play the vital role in terms of the toxicity. At the given concentration, QXG-1 displayed the safety against PC12 (10.0 µg/mL) in vitro and mice (3.2 mg/kg) in acute toxicity test, and strong inhibitory effect on Na+-K+-ATPase. It could be used as a promising acaricidal agent. This study lays the foundation to develop of QXG-1 as a relatively safe and alternative acaricidal agent.


Subject(s)
Acaricides , Psoroptidae , Strophanthidin , Acaricides/pharmacology , Adenosine Triphosphatases/metabolism , Adonis/chemistry , Animals , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Mice , Psoroptidae/drug effects , Strophanthidin/pharmacology
2.
Vet Parasitol ; 286: 109247, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32987229

ABSTRACT

Adonis coerulea Maxim. presents acaricidal activity in vitro and in vivo, and inhibits AChE and other enzymes activities. However, the active compounds against Psoroptes cuniculi were still unclear. AChE, a common acaricidal and insecticidal target, plays a key role in neural conduction of mites. In this study, using surface plasmon resonance (SPR) technology, AChE was used as a target to capture the compounds from A. coerulea methanol extract (MEAC). After calculating the affinity with molecular docking, the inhibitory effect of compounds against AChE was studied. Results showed that 27 compounds were captured by AChE and identified from MEAC by LC-MS/MS. Among of these compounds, eight compounds presented the high affinity with AChE and high scores in molecular docking assay, especially for silibinin (-12.19 kcal/mol) and vitexin (-11.72 kcal/mol). Further studies showed that although these compounds have the weak cytotoxicity against C6/36 cells, silibinin, quercetin and corilagin could inhibit AChE activity with IC50 values of 40.11 µg/mL, 46.15 µg/mL and 50.98 µg/mL, respectively. These results indicated that silibinin, quercetin and corilagin may be responsible for AChE inhibition which contributes to the acaricidal properties of A coerulea. This study lays the foundation for developing sensitive and sustainability methods for active compound detection from plants.


Subject(s)
Acaricides/pharmacology , Adonis/chemistry , Cholinesterase Inhibitors/pharmacology , Plant Extracts/pharmacology , Psoroptidae/drug effects , Animals , Cholinesterase Inhibitors/chemistry , Molecular Docking Simulation , Plant Extracts/chemistry
3.
Exp Parasitol ; 218: 107998, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32941889

ABSTRACT

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations.


Subject(s)
Insecticides/therapeutic use , Ivermectin/analogs & derivatives , Mite Infestations/veterinary , Psoroptidae/drug effects , Sheep Diseases/drug therapy , Animals , Biological Availability , Female , Half-Life , Injections, Subcutaneous/veterinary , Insecticides/administration & dosage , Insecticides/blood , Insecticides/pharmacology , Ivermectin/administration & dosage , Ivermectin/blood , Ivermectin/pharmacology , Ivermectin/therapeutic use , Male , Mite Infestations/drug therapy , Psoroptidae/growth & development , Sheep , Sheep Diseases/parasitology
4.
Parasitol Res ; 119(12): 4219-4223, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32725319

ABSTRACT

Essential oils and their components represent an appealing alternative strategy against parasitic mites. The chemical complexity and variability of essential oils limit their use and additional work is required to analyze the efficacy and application rate of essential oils' individual components. In the present study, the activity of five terpenes (terpinen-4-ol, citral, linalool, eugenol, and geraniol) was evaluated against Psoroptes cuniculi motile stages and eggs collected from naturally infected rabbits. Eugenol presented the best acaricidal efficacy with a median lethal concentration (LC50) value of less than 0.1% at 24 h, followed by geraniol (0.33%), linalool (0.38%), citral (0.46%), and terpinen-4-ol (0.66%). Geraniol and eugenol were able to kill all mites within 5 min at 1% concentration. The effective concentration to inhibit 50% (EC50) of egg hatching was 0.65%, 0.66%, 0.85%, 1.47%, and 2.87% for eugenol, geraniol, citral, terpinen-4-ol, and linalool, respectively. In conclusion, eugenol, geraniol, citral, terpinen-4-ol, and linalool should be considered as promising agents for the development of botanical acaricides against Psoroptes cuniculi.


Subject(s)
Acaricides/pharmacology , Oils, Volatile/pharmacology , Psoroptidae/drug effects , Terpenes/pharmacology , Animals , Lethal Dose 50 , Mite Infestations/drug therapy , Mite Infestations/parasitology , Ovum/drug effects , Parasitic Sensitivity Tests , Rabbits
5.
Vet Parasitol ; 279: 109059, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32112975

ABSTRACT

The entomopathogenic fungi Metarhizium anisopliae is highly pathogenic toward arthropods. Here, we evaluated the efficacy of a commercial formulation of M. anisopliae against P. ovis var. cuniculi in vivo and in vitro and explored the acaricidal mechanism of M. anisopliae by determining the antioxidant/detoxification-related enzymes activities including glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in mites. The results showed that M. anisopliae had high acaricidal activity against P. ovis var. cuniculi in vitro, in a time- and dose-dependent manner, with 83.33 % mortality at day 9 and a median lethal time (LT50) of 6.10 days after applying 6.14 × 109 conidia/ml of M. anisopliae. In vivo experiments, M. anisopliae achieved 100 % therapeutic effect after 3 days, compared with only 62.21 % for ivermectin. Enzyme assays showed that M. anisopliae significantly upregulated activities of GST, SOD and CAT in Psoroptes mites. The results indicate that M. anisopliae may be an effective biological agent for control of P. ovis var. cuniculi infestations in rabbits and the acaricidal activity may be associated with the changes of enzyme activities of the detoxification and antioxidant system in Psoroptes mites.


Subject(s)
Acaricides/therapeutic use , Metarhizium/chemistry , Mite Infestations/veterinary , Psoroptidae/drug effects , Animals , Antioxidants/metabolism , Female , Male , Mite Infestations/parasitology , Mite Infestations/prevention & control , Rabbits
6.
Parasit Vectors ; 13(1): 127, 2020 Mar 14.
Article in English | MEDLINE | ID: mdl-32169109

ABSTRACT

BACKGROUND: Psoroptic mange is an important disease in Belgian Blue cattle. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is lacking. This study assessed the efficacy of macrocyclic lactone products on 16 beef farms in Belgium and the Netherlands in vivo and in vitro. METHODS: On each farm a group of animals (n = 7-14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts, clinical index (proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population was categorized as sensitive when the mite count reduction after the first treatment round > 95% and the lower limit of the uncertainty interval > 90%. Resistance was detected when both parameters were below their threshold and suspected when one parameter was too low. In vitro knockdown and mortality were evaluated in a contact test. RESULTS: The proportion of the animals with negative mite counts after the first treatment round varied from 0 to 80%. All farms needed two or more treatments rounds to obtain zero mite counts on all animals. Clinical index only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and 12 as resistant. No correlation was found between in vitro lethal dose 50 and knockdown dose 50 values and in vivo efficacy parameters. CONCLUSIONS: Unambiguous treatment failure was detected on 12 out of 16 farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as parameters to identify acaricide resistance.


Subject(s)
Cattle Diseases/parasitology , Drug Resistance , Lactones/pharmacology , Mite Infestations/veterinary , Psoroptidae/drug effects , Acaricides/pharmacology , Animals , Belgium , Cattle , Cattle Diseases/drug therapy , Farms , Female , Injections, Subcutaneous , Lethal Dose 50 , Male , Mite Infestations/drug therapy , Netherlands , Treatment Outcome
7.
Vet Parasitol ; 272: 79-82, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31395209

ABSTRACT

The astigmatid mite Psoroptes ovis (Acari: Proroptidae) causes the highly contagious and debilitating ovine disease, sheep scab. This ectoparasitic infection has a high economic and animal welfare impact on British sheep farming. Following recent work demonstrating resistance of Psoroptes mites to moxidectin, a widely used macrocyclic lactone (ML) treatment for scab, the current study compared the toxicity of three of the commonly administered macrocylic lactone therapeutic treatments (moxidectin, ivermectin and doramectin) to P. ovis from outbreak populations that had appeared unresponsive to treatment. These outbreak populations were from Wales and south west England. The data presented demonstrate that there is resistance to all three available ML compounds in populations of Psoroptes mites. However, considerable variation in response suggested that resistance alone was not responsible for the reported lack of efficacy in all of the submitted cases; lack of response in others may be associated with inappropriate treatment application or management. These data highlight the importance of the appropriate use of these compounds to manage national scab incidence at levels that are consistent with acceptable animal welfare standards, while attempting to reduce the development and spread of resistance.


Subject(s)
Drug Resistance, Multiple , Lactones/administration & dosage , Lactones/pharmacology , Mite Infestations/veterinary , Psoroptidae/drug effects , Animal Husbandry/standards , Animals , Antiparasitic Agents/administration & dosage , Antiparasitic Agents/pharmacology , England , Mite Infestations/drug therapy , Mite Infestations/epidemiology , Mite Infestations/prevention & control , Sheep , Sheep Diseases/drug therapy , Sheep Diseases/epidemiology , Sheep Diseases/prevention & control , Wales
8.
Parasit Vectors ; 12(1): 425, 2019 Aug 29.
Article in English | MEDLINE | ID: mdl-31464634

ABSTRACT

BACKGROUND: Treatment of Psoroptes ovis in cattle is limited to topical acaricides or systemic treatment with macrocyclic lactones. Treatment failure of macrocyclic lactones has been reported. The aim of this study was to evaluate a potential alternative treatment against P. ovis. METHODS: The acaricidal activity against P. ovis of four plant-derived essential oil components, i.e. geraniol, eugenol, 1,8-cineol and carvacrol, was assessed in vitro and in vivo. In vitro contact, fumigation and residual bioassays were performed. In addition, 12 Belgium Blue cattle were artificially infested and treated topically once a week for three successive weeks with carvacrol in Tween-80 (treatment group) or with Tween-80 alone (control). The efficacy of carvacrol was determined by the reduction in lesion size and mite counts. Six additional animals were topically treated with carvacrol to assess local adverse reactions. RESULTS: Three components showed a concentration-dependent acaricidal activity in a contact assay, with LC50 of 0.56, 0.38 and 0.26% at 24 h for geraniol, eugenol, and carvacrol, respectively. However, 1,8-cineol showed no activity at any of the tested concentrations in a contact bioassay. In a fumigation bioassay, carvacrol killed all mites within 50 min after treatment, whereas geraniol, eugenol and 1,8-cineol needed 90 to 150 min. Following a 72 h incubation period in a residual bioassay, carvacrol killed all mites after 4 h of exposure to LC90, while geraniol and eugenol killed all mites only after 8 h exposure. Based on these results, carvacrol was further assessed in vivo. Mite counts in the treatment group were reduced by 98.5 ± 2.4% at 6 weeks post-treatment, while in the control group the mite population had increased. Topical application of carvacrol only caused mild and transient erythema 20 min after treatment. No other side effects were observed. CONCLUSIONS: Considering the strong acaricidal activity of carvacrol in vitro and in vivo and the mild and transient local side effects, carvacrol shows potential as an acaricidal agent in the treatment of P. ovis in cattle.


Subject(s)
Acaricides/therapeutic use , Cattle Diseases/drug therapy , Mite Infestations/veterinary , Oils, Volatile/therapeutic use , Plant Extracts/therapeutic use , Psoroptidae/drug effects , Acyclic Monoterpenes/therapeutic use , Animals , Cattle , Cattle Diseases/parasitology , Cymenes/therapeutic use , Eucalyptol/therapeutic use , Eugenol/therapeutic use , Female , Fumigation , Lethal Dose 50 , Male , Mite Infestations/drug therapy
9.
Vet Parasitol ; 267: 54-59, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30878086

ABSTRACT

Plant essential oils and its chemical compositions are commonly applied in medicinal and other industries due to their broad advanced pharmacological activities. In the present study, we systematically evaluated the acaricidal activities of twelve compounds of essential oils against Psoroptes cuniculi in vitro and in vivo. In addition, to support the clinic uses, their toxicities against immortalized human keratinocytes (HaCaT) and human liver cells (HL-7702) and skin irritation were studied for evaluating the liver and skin safety. The possible mechanism of action of certain chemical were investigated by determining the inhibitory activities against cytochrome P450 (P450) acetylcholinesterase (AChE) and glutathione-S-transferase (GST). Among all tested compounds, eugenol exhibited the best acaricidal activity with LC50 value of 56.61 µg/ml in vitro. Meanwhile, after the treatment of eugenol for five times within 10 days, the P. cuniculi were eliminated in the naturally infested rabbits, no skin irritation was found in rabbits treated by eugenol. Moreover, eugenol presented no or weak cytotoxicity against HaCaT cells and HL-7702 cells with IC50 values of greater than 100 µg/ml. Furthermore, the moderate inhibitory activities of eugenol against mites P450 and AChE were demonstrated. Above results indicated that eugenol presented the promising acaricidal activity against P. cuniculi in vitro and in vivo, is safe for both humans and animals at the given doses. This work lays the foundation for the development of eugenol as an environmentally friendly acaricide agent.


Subject(s)
Acaricides/pharmacology , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Psoroptidae/drug effects , Acaricides/adverse effects , Acetylcholinesterase/analysis , Animals , Cell Line , Eugenol/pharmacology , Glutathione Transferase/analysis , Humans , Inhibitory Concentration 50 , Keratinocytes/drug effects , Liver/cytology , Liver/drug effects , Mite Infestations/drug therapy , Oils, Volatile/adverse effects , Plant Extracts/adverse effects , Rabbits
10.
Vet Parasitol ; 266: 56-62, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30736947

ABSTRACT

In this study, the acaricidal effect of eugenol was measured and its mechanism of action investigated. The results showed that eugenol possessed the effect of killing Psoroptes cuniculi, and could regulate the mRNA expression of glutathione S-transferase (GST), catechinic acid (Ca) and thioredoxin (Trx). PPAR, NF-kappa B, TNF, Rap 1 and Ras signaling pathways might be the main pathways that involved into the process of killing mites. These findings suggested that eugenol could be developed into a new kind of acaricide, and further expand current knowledge on the mechanisms of eugenol for killing Psoroptes cuniculi of eugenol.


Subject(s)
Acaricides/pharmacology , Eugenol/pharmacology , Psoroptidae/drug effects , Animals , Catechin/genetics , Gene Expression Profiling , Glutathione Transferase/genetics , Plant Extracts/pharmacology , Psoroptidae/genetics , Signal Transduction/drug effects
11.
Vet Parasitol ; 263: 18-22, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30389019

ABSTRACT

Psoroptic mange is an important parasitic disease that mainly affects beef cattle producing marked economic losses. Ivermectin (IVM) is considered one of the most effective treatments against psoroptic mange and is used worldwide to control both endo and ectoparasites in different species. The current work assessed the relationship between pharmacokinetic behavior of IVM and its efficacy against Psoroptes ovis after the subcutaneous administration of two commercial formulations in a cattle feedlot. Aberdeen Angus and Hereford steers were selected based on the presence of active mite infestations. Animals were allocated into 4 experimental groups and treated with a single (day 0) or repeated subcutaneous injection (days 0 and 7) of one of two commercial formulations of IVM (1%) at 0.2 mg/kg. Blood and skin samples were taken from 8 randomly selected animals of each experimental group to measure IVM concentrations by HPLC. Skin scrapings were also collected from six different sites in each animal, mites were counted and ranked based on a density score. Equivalent plasma concentrations of IVM were measured after the administration of IVM formulations under study. The repeated administration of both IVM formulations at day 0 and 7 accounted for a greater plasma drug availability compared with the single administration (P < 0.05). IVM was well distributed from the plasma to the skin without significant differences between both IVM formulations. There was a positive correlation between IVM concentrations in skin and plasma (r: 0.73 P < 0.0001). The mean ratios between IVM availabililty (measured as AUC) in the skin and in plasma were between 1.2 and 2.1. The repeated administration of IVM increased significantly the IVM concentrations in the skin of areas affected by mange. IVM failed to obtain a parasitological cure in the different groups affected by mange. The failure was observed with both formulations administeredat single or repeated doses. Based on the number of animals cured, the range of efficacy was between 0% on day 7 and 60% on day 28 post-treatment. No significant differences in the P. ovis density scores were observed after the IVM treatment at single or repeated doses. Additional studies are needed to confirm the presence of resistant strains of P.ovis and to establish the appropriate measures to control these parasitic infestations in feedlot cattle.


Subject(s)
Drug Compounding , Ivermectin/pharmacokinetics , Ivermectin/therapeutic use , Mite Infestations/veterinary , Mites/drug effects , Psoroptidae/drug effects , Treatment Failure , Animals , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/parasitology , Injections, Subcutaneous , Ivermectin/administration & dosage , Mite Infestations/drug therapy , Parasitic Diseases, Animal/drug therapy , Skin/parasitology
12.
Parasit Vectors ; 11(1): 595, 2018 Nov 19.
Article in English | MEDLINE | ID: mdl-30449272

ABSTRACT

BACKGROUND: The efficacy of the fixed combination of fluralaner plus moxidectin for the treatment of Otodectes cynotis infestations was evaluated in cats after topical application. METHODS: Sixteen cats experimentally infested with O. cynotis were allocated randomly to two groups of 8 cats each. One group was treated topically with the fixed combination of fluralaner plus moxidectin at the minimum dose rate of 40 mg fluralaner and 2 mg moxidectin/kg body weight. The other group was treated with physiological saline solution. Before and 14 and 28 days after treatment the ears of all cats were examined otoscopically for live mites and for the amount of debris and cerumen. Twenty-eight days after treatment, the cats were sedated and had both ears flushed to obtain the total number of live mites per animal. Efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner plus moxidectin treated group versus the saline group. RESULTS: A single topical application of the fixed combination of fluralaner plus moxidectin to cats reduced the mean mite counts by 100% (P < 0.001) by 28 days after treatment. No mites were visible during otoscopic examination at either 14 or 28 days after treatment. All fluralaner plus moxidectin treated cats had less ceruminous exudate 28 days after treatment compared to pre-treatment and 14 days after treatment. No treatment related adverse events were observed in any cats enrolled in the study. CONCLUSIONS: Single topical application of the fixed combination of fluralaner plus moxidectin was highly effective against O. cynotis infestations in cats.


Subject(s)
Cat Diseases/drug therapy , Insecticides/therapeutic use , Isoxazoles/therapeutic use , Macrolides/therapeutic use , Mite Infestations/veterinary , Psoroptidae/drug effects , Administration, Topical , Animals , Cat Diseases/epidemiology , Cat Diseases/parasitology , Cats , Drug Therapy, Combination , Female , Insecticides/administration & dosage , Isoxazoles/administration & dosage , Macrolides/administration & dosage , Male , Mite Infestations/drug therapy , Mite Infestations/epidemiology , Otitis Externa/drug therapy , Otitis Externa/parasitology , Otitis Externa/veterinary , Otoscopy/veterinary , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/therapeutic use , Random Allocation , Treatment Outcome
13.
Drug Dev Ind Pharm ; 44(12): 2000-2004, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30058406

ABSTRACT

BACKGROUND: Psoroptes cuniculi mites are the most common ear parasites infesting breeding female rabbits. The suffering rabbits show cutaneous signs of the infestation in the ears and are prone to secondary infections. OBJECTIVES: This trial was conducted to eliminate P. cuniculi in farm rabbits with a sustained-release ivermectin-loaded solid dispersion suspension (IVM-SD) suspension, and studied the stability of the formulation. ANIMALS: There were 986 breeding female Hyplus rabbits naturally infected with P. cuniculi. METHODS: All rabbits infected with P. cuniculi were subcutaneously administered with a single dose of IVM-SD suspension at 2 mg/kg body weight. Twenty-seven rabbits with severe infections were observed daily and examined on days 0 and 14 to score the lesions and count mites in crusts. RESULTS: Fourteen days after the treatment no live mites were detected, demonstrating 100% therapeutic efficacy. The mean lesion scores decreased from 4.33 to 0.11 in the left ears and from 4.22 to 0.22 in the right ears. No reinfection occurred within 60 days of treatment. CONCLUSIONS: A single subcutaneous administration of the IVM-SD suspension at 2 mg/kg was effective in eliminating P. cuniculi infection in the rabbit farm.


Subject(s)
Antiparasitic Agents/administration & dosage , Ivermectin/administration & dosage , Mite Infestations/drug therapy , Mite Infestations/veterinary , Psoroptidae/drug effects , Animal Husbandry/methods , Animals , China , Delayed-Action Preparations/administration & dosage , Ear/parasitology , Ear/pathology , Farms , Female , Injections, Subcutaneous , Mite Infestations/parasitology , Mite Infestations/pathology , Psoroptidae/pathogenicity , Rabbits , Random Allocation , Skin/parasitology , Skin/pathology , Suspensions , Treatment Outcome
14.
Bioorg Med Chem Lett ; 28(6): 1149-1153, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29496368

ABSTRACT

A series of cinnamic acid derivatives and its heteroaromatic ring analogues were synthesized and evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange mite. Among them, eight compounds showed the higher activity with median lethal concentrations (LC50) of 0.36-1.07mM (60.4-192.1µg/mL) and great potential for the development of novel acaricidal agent. Compound 40 showed both the lowest LC50 value of 0.36mM (60.4µg/mL) and the smallest median lethal time (LT50) of 2.6h at 4.5mM, comparable with ivermectin [LC50=0.28mM (247.4µg/mL), LT50=8.9h], an acaricidal drug standard. SAR analysis showed that the carbonyl group is crucial for the activity. The type and chain length of the alkoxy in the ester moiety and the steric hindrance near the ester group significantly influence the activity. The esters were more active than the corresponding thiol esters, amides, ketones or acids. Replacement of the phenyl group of cinnamic esters with α-pyridyl or α-furanyl significantly increase the activity. Thus, a series of cinnamic esters and its heteroaromatic ring analogues with excellent acaricidal activity emerged.


Subject(s)
Acaricides/pharmacology , Cinnamates/pharmacology , Psoroptidae/drug effects , Acaricides/chemical synthesis , Acaricides/chemistry , Animals , Cinnamates/chemical synthesis , Cinnamates/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship
15.
Vet Dermatol ; 29(2): 100-e39, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29392787

ABSTRACT

BACKGROUND: Various treatments are available for ear mite infestations in dogs. OBJECTIVE: The efficacy of sarolaner was evaluated against ear mite infestation caused by Otodectes cynotis in dogs and compared with topical moxidectin/imidacloprid in a single-masked, multi-centre field study. ANIMALS: Client-owned dogs with O. cynotis infestation were treated monthly with oral sarolaner (n = 163) or topical moxidectin/imidacloprid (n = 78). METHODS: The presence of mites in the ear canals and the clinical signs associated with otoacariasis (including head shaking, pruritus/ear scratching, trauma or alopecia of the pinnae, and erythema, ulceration and debris in the ear canals) was evaluated on days 0, 14 and 30, and, if applicable, on day 60. Dogs were considered cured of mite infestation following one (on day 0) or two (on days 0 and 30) monthly treatments, if no live mites were found in either ear. Non-inferiority was evaluated at days 14 and 30. RESULTS: Parasitological cure was achieved in 76.4%, 90.5% and 93.3% of the sarolaner-treated and in 53.9%, 63.5% and 66.7% of the moxidectin/imidacloprid-treated dogs on days 14, 30 and 60, respectively. At study completion, on day 60 at the latest, parasitological cure was achieved overall in 99.4% of sarolaner-treated and 87.8% of moxidectin/imidacloprid-treated cases. The parasitological cure rate for sarolaner was non-inferior to moxidectin/imidacloprid at days 14 and 30. The clinical signs of otoacariasis improved throughout the study in both groups. There were no treatment-related adverse events. CONCLUSIONS: A single oral administration of sarolaner was safe and highly effective in the treatment of O. cynotis infestation in dogs.


Subject(s)
Azetidines/adverse effects , Dog Diseases/drug therapy , Mite Infestations/veterinary , Psoroptidae/drug effects , Spiro Compounds/adverse effects , Administration, Oral , Administration, Topical , Animals , Azetidines/administration & dosage , Azetidines/therapeutic use , Dogs , Drug-Related Side Effects and Adverse Reactions , Female , Insecticides/administration & dosage , Insecticides/therapeutic use , Isoxazoles/administration & dosage , Isoxazoles/therapeutic use , Macrolides/administration & dosage , Macrolides/therapeutic use , Male , Mite Infestations/drug therapy , Pets , Psoroptidae/parasitology , Spiro Compounds/administration & dosage , Spiro Compounds/therapeutic use
16.
Sci Rep ; 8(1): 1797, 2018 01 29.
Article in English | MEDLINE | ID: mdl-29379066

ABSTRACT

A series of 3-aryl propionic esters and their analogues were designed and evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange mite. The structure-activity relationship (SAR) was also discussed. The results showed that 6 compounds possessed the excellent activity (LC50 = 0.17-0.24 mM, LT50 = 1.5-2.9 h), superior to ivermectin (LC50 = 0.28 mM, LT50 = 8.9 h) (P < 0.05), a standard drug. Furthermore, 7 compounds showed the good activity (LC50 = 0.25-0.37 mM, LT50 < 3.9 h), slightly lower or close to that of ivermectin. One compound displayed super-fast acaricidal property, far superior to ivermectin. SAR analysis found that the ester group is vital for the activity and the small steric hindrance adjacent to the ester group is advantageous for the high activity. The

Subject(s)
Acaricides/pharmacology , Esters/pharmacology , Psoroptidae/drug effects , Animals , Dose-Response Relationship, Drug , Ivermectin/pharmacology , Structure-Activity Relationship
17.
Vet Rec ; 182(4): 106, 2018 01 27.
Article in English | MEDLINE | ID: mdl-29317477

ABSTRACT

Ovine psoroptic mange (sheep scab) is an infection of substantial economic and animal welfare concern in the UK. Its prevalence has increased rapidly over the last 20 years and management is dependent on a small number of acaricidal compounds, many of which are also used to control a range of other endoparasites and ectoparasites. Here, the effects of the macrocyclic lactone (ML) moxidectin was considered using in vitro assays against mites from four farm populations where persistent treatment failure had been reported: two in West Wales, one from the England/Wales border and one in Herefordshire. The data demonstrate resistance in mites from all four farms. This is the first quantitative evidence of ML resistance in Psoroptes mites in the UK. Given the similarities in their mode of action it is highly likely that cross-resistance across the range of this class of compound will be found. The development of resistance to moxidectin is of considerable concern given the already high prevalence of scab infection in some regions; major difficulties in scab management should be anticipated if ML resistance becomes widely established in the UK.


Subject(s)
Macrolides/pharmacology , Mite Infestations/veterinary , Psoroptidae/drug effects , Sheep Diseases/drug therapy , Animals , Macrolides/therapeutic use , Mite Infestations/drug therapy , Prevalence , Sheep , United Kingdom/epidemiology
18.
Sci Rep ; 8(1): 1609, 2018 01 25.
Article in English | MEDLINE | ID: mdl-29371639

ABSTRACT

As important secondary plant metabolites, naphthoquinones exhibit a wide range of biological activities. However, their potential as sustainable alternatives to synthetic acaricides has not been studied. This study for the first time investigates the acaricidal activity of naphthoquinones against Psoroptes cuniculi in vitro. Furthermore, the in vivo activity, the skin irritation effects, the cytotoxicity and the inhibitory activities against mite acetylcholinesterase (AChE) and glutathione S-transferase (GST) of the two compounds that displayed the best insecticidal activity in vitro were evaluated. Among fourteen naphthoquinones and their analogs, juglone and plumbagin were observed to possess the strongest acaricidal activities against P. cuniculi with LC50 values of 20.53 ppm and 17.96 ppm, respectively, at 24 h. After three treatments, these two chemicals completely cured naturally infested rabbits in vivo within 15 days, and no skin irritation was found in any of the treated rabbits. Compared to plumbagin, juglone presented no or weak cytotoxicity against HL-7702 cells. Moreover, these two chemicals significantly inhibited AChE and GST activity. These results indicate that juglone has promising toxicity against P. cuniculi, is safe for both humans and animals at certain doses, and could be used as a potential alternative bio-acaricide for controlling the development of psoroptic mange in agricultural applications.


Subject(s)
Acaricides/pharmacology , Agriculture/methods , Naphthoquinones/pharmacology , Phytochemicals/pharmacology , Psoroptidae/drug effects , Acaricides/administration & dosage , Animals , Biological Assay , Cell Survival/drug effects , Cholinesterase Inhibitors/pharmacology , Disease Models, Animal , Glutathione Transferase/antagonists & inhibitors , Mite Infestations/drug therapy , Naphthoquinones/administration & dosage , Phytochemicals/administration & dosage , Rabbits , Skin/drug effects , Survival Analysis , Treatment Outcome
19.
Pol J Vet Sci ; 20(3): 521-525, 2017 Sep 26.
Article in English | MEDLINE | ID: mdl-29166286

ABSTRACT

The ear mite "Psoroptes cuniculi" is the main cause of ear mange, a highly contagious parasitic skin disease in rabbits all over the world. In the current work, a preliminary therapeutic trial to study the effect of the broad use acaricides doramectin and ivermectin on P. cuniculi was performed on artificially infested rabbits. Twenty five adult New Zealand white rabbits were used in this study. The rabbits were assigned randomly into five groups/ 5 rabbits in each group. Each rabbit was experimentally infested with 100 mites/ ear. The first group was designated the positive control group and was not treated. The second and third groups were treated with doramectin 200 and 400 µg/kg bw, respectively. Groups 4 and 5 were treated by dressing with ivermectin in one dose and 2 doses with a 1 week interval. After the therapy, all rabbits were examined microscopically on the 7th, 14th, and 28th day post treatment and the number of live mites (larvae, nymphs, and adults) on each rabbit was counted at the end of the experiment (28th day). The results showed that the rabbits treated subcutaneously with doramectin at a single dose of 200 µg /kg bw showed a very low effect, although there was significant improvement when the dose was doubled to 400 µg /kg bw, with the number of mites counted decreasing significantly. Rabbits treated topically with ivermectin spot-on, a single dose or 2 doses, showed great improvement of the lesion: the number of mites was reduced to zero. In conclusion, this work showed that ivermectin spot-on applied locally on infested ears proves to be more effective against P. cuniculi than doramectin injected subcutaneously. Further trials on ear mange therapeutics in rabbits are to be encouraged.


Subject(s)
Ivermectin/analogs & derivatives , Ivermectin/therapeutic use , Mite Infestations/veterinary , Psoroptidae/drug effects , Rabbits/parasitology , Administration, Topical , Animals , Injections, Subcutaneous , Insecticides/administration & dosage , Insecticides/therapeutic use , Ivermectin/administration & dosage , Mite Infestations/drug therapy , Random Allocation
20.
Vet Dermatol ; 28(6): 622-e152, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28691193

ABSTRACT

BACKGROUND: African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. OBJECTIVE: To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. ANIMALS: A 10-month-old African pygmy hedgehog weighing 184 g. METHODS: Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. RESULTS: On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. CONCLUSION AND CLINICAL IMPORTANCE: A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy.


Subject(s)
Acaricides/therapeutic use , Hedgehogs/parasitology , Isoxazoles/therapeutic use , Mite Infestations/veterinary , Psoroptidae/drug effects , Acaricides/administration & dosage , Administration, Oral , Animals , Isoxazoles/administration & dosage , Male , Mite Infestations/diagnosis , Mite Infestations/drug therapy
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