A kaempferol derivative isolated from Lysimachia ramosa (Wall ex. Duby) induced alteration of acetyl cholinesterase and nitric oxide synthase in Raillietina echinobothrida.

Lysimachia ramosa has been used as a traditional medicine among the tribal population of Meghalaya, northeast India, for the control of helminthosis. The anthelmintic efficacy of L. ramosa has been documented earlier. In the present study, the active compound from L. ramosa has been isolated and identified using mass and NMR spectra. It's in vitro anthelmintic activity was evaluated against Raillietina echinobothrida, one of the most pathogenic cestode of domestic fowl. The isolated active compound was characterized to be a kaempferol derivative which showed potent anthelmintic activity against R. echinobothrida by changing surface ultrastructure and also inhibiting the activity of two neurotransmitter enzymes: acetyl cholinesterase (AChE) and nitric oxide synthase (NOS), both of which are known to perform dynamic roles in the intracellular communication mediated through neuromuscular system. Motility reduction, deformation in the surface architecture, extensive ultrastructural alterations and reduced histochemical stain intensity in both AChE and NOS was observed in the treated parasites. Biochemical result also revealed alteration in the enzyme activities in the treated parasites. Further, depletion in the nitric oxide (NO) production in the bioactive component exposed tissues of R. echinobothrida was also detected. The results provided evidence that the bioactive compound could be further explored to control helminthosis at a large scale.

Unravelling the anthelmintic bioactives from Jasminum grandiflorum L. subsp. Floribundum adopting in vitro biological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum grandiflorum L. is a medicinal plant widely used in the traditional system of Medicine as an anthelmintic in ringworm infections, for treating ulcers, stomatitis, skin diseases, and wounds. AIM OF THE STUDY: The emergence of resistance by different parasites to currently used chemicals has been reported. There are increasing needs for more effective and safer parasiticides. Therefore, the current study was designed to investigate the methanolic extract of the aerial parts of J. grandiflorum subsp. Floribundum (JGTE) to confirm its traditional uses as anthelmintic through a bioassay-guided fractionation and isolation of the active components with anthelmintic activity. MATERIALS AND METHODS: The JGTE was partitioned into dichloromethane (DCM-F) and n-butanol (BuOH-F) fractions. The JGTE, fractions, and the isolated compounds were tested in vitro for their anthelmintic activity using two nematodes; one larval stage of cestode and one arthropod. Four major compounds were isolated from the most active fraction (BuOH-F) including two flavonoids and two secoirridoid glycosides, identified as kaempferol-3-O-neohesperoside (1), rutin (2), oleuropein (3), and ligstroside (4). RESULTS: Among the isolated compounds from most active fraction (BuOH-F), rutin (2) displayed the highest anthelmintic activity in a dose-dependent activity with IC50 of 41.04 µg/mL against H. muscae adult worm, followed by ligstroside (4) with IC50 of 50.56 µg/mL. CONCLUSIONS: These findings could advocate the traditional use of J. grandiflorum L. and provide further insight into the anthelmintic activity of flavonoids.

Phytochemical analysis and in vitro anthelmintic activity of Imperata cylindrica underground parts.

BACKGROUND: Imperata cylindrica is considered as an agricultural weed, but it is a valuable plant in the traditional medicines of Southeast Asia. In the Mizo traditional medicine of India and Myanmar, the rhizomes and roots are used as a remedy for bacterial, fungal and intestinal helminth infections. METHODS: An extract of the whole underground parts was prepared in Soxhlet apparatus using chloroform as a solvent. After concentrating in a vacuum rotary evaporator, the extract was analysed using gas chromatography-mass spectrometry. Anthelmintic activity was tested in vitro against the tapeworm Raillietina tetragona and the roundworm Ascaridia galli. Scanning electron microscopy was used to examine the structural changes on the helminths after treatment with the plant extract. RESULTS: Twenty-two compounds were identified from the plant extract out of which fatty acids were the predominant compounds. Palmitic acid was the most abundant. Bioactive phytosterols such as campesterol and stigmasterol were also detected. The plant extract was significantly effective on both the helminths and showed dose-dependent anthelmintic activity as that of albendazole. The tapeworm treated with the plant extract showed deformities on the suckers, clumping of the spines, tegumental folds and erosion of microtriches. Extensive damage was also seen on the roundworm including cuticular shrinkage, collapse of the lips, and formation of warty surface throughout the body. CONCLUSION: I. cylindrica extract effectively killed and caused detrimental effects on parasitic tapeworm and roundworm. The study therefore validates the traditional usage among the Mizo people, and guarantees further investigation on the exact compound(s) and mechanism of action.

Morphological abnormalities in fish parasites: a potential tool for biomonitoring natural contaminants?

A comparative study on the strobilar morphology of the tapeworm Proteocephalus percae (Müller, 1780) (Cestoda), a parasite of the perch Perca fluviatilis (L.), showed a high percentage of abnormally developed parasite individuals. The evaluation of biological samples showed seven types of morphological abnormalities, mostly related to reproductive organs of the model tapeworm species. The most commonly identified deformity was an incomplete segmentation of the strobila. A malformed ovary, which is a structural anomaly linked with proglottization and maturation of the strobila, was also shown to be rather frequent. Offish hosts (P. percae) were collected from two localities with different levels of heavy metal pollution, the highly contaminated water reservoir Ruzín and a control locality, the water reservoir Palcmanská Masa, which belongs to the European network of protected areas in Slovakia. Tapeworm abnormalities occurred more frequently in individuals from the contaminated environment (29.9%) compared with individuals from the control site (4.9%). The concentrations of heavy metals found in the parasites and their fish hosts from the heavily polluted reservoir support our assumption that the occurrence of abnormalities could be linked with the destructive effect of toxic substances. The present study also demonstrates that the enumeration of body deformities exceeding the common level of phenotypic variability of particular parasitic species could potentially be used as an indicator of environmental problems.

Activation of transient receptor potential channel Sm.(Schistosoma mansoni)TRPMPZQ by PZQ, enhanced Ca++ influx, spastic paralysis, and tegumental disrupture-the deadly cascade in parasitic schistosomes, other trematodes, and cestodes.

After almost 50 years of praziquantel (PZQ) research, Park and Marchant (Trends Parasitol 36:182-194, 2020) described the Ca++-permeable transient receptor potential (TRP) channel Sm.TRPMPZQ in Schistosoma mansoni as target of PZQ. Here we describe the deadly cascade in schistosomes which is induced by the (R)-PZQ enantiomer that includes contemporaneous stereoselective activation of Sm.TRPMPZQ-mediated Ca++ influx, disturbed Ca++ homeostasis, Ca++-dependent spastic paralysis, and Ca++- and PZQ-dependent disruption of parasitic teguments. Under normal conditions, there is a reversible balance between bilayer, isotropic, and HII phases in biological membranes (Jouhet 2013). In vitro, we could observe an irreversible but not stereoselective transition to the HII phase in liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS), two naturally occurring phospholipids in schistosomes, by the concerted action of Ca++ and PZQ (Harder 2013). HII structures are a prerequisite for induction of fusion processes (Jouhet 2013), which, indeed, become visible as blebs, vacuolation processes, and large balloon-like surface exudates in a large variety of PZQ-sensitive parasitic flukes and cestodes after PZQ treatment. These tegument damages are irreversible. As homologs of Sm.TRPMPZQ are also present in the other trematodes S. japonicum, S. haematobium, or Clonorchis sinensis and cestodes Taenia solium, Echinococcus multilocularis, or Hymenolepis microstoma (Park and Marchant, Trends Parasitol 36:182-194, 2020), it is suggested that a similar deadly cascade will be operating generally in PZQ-sensitive parasites.

Anthelmintic activity of praziquantel and Spilanthes acmella extract on an intestinal cestode parasite.

Spilanthes acmella Murr., popularised as toothache plant, is a well-known culinary and medicinal plant for different purposes, but its use as an anthelmintic is apparently exclusive to the Mizo people of India and Myanmar. A chloroform extract of Spilanthes acmella Murr. was analysed in a single quadrupole GC-MS system, from which it was found that the major compound was an alkylamide, N-isobutyl-(2E,4Z,8Z,10E)-dodecatetraenamide. A comparative study was performed on the anthelmintic activity of the plant extract and praziquantel (PZQ) against an intestinal cestode, Raillietina echinobothrida. In terms of efficacy, PZQ was more potent, but the plant extract was also effective at all concentrations tested. PZQ caused severe shrinkage and folds of the tegument, constriction of the suckers, dislocation of spines and erosion of microtriches. The plant extract caused shrinkage and folds on the main body but not on the scolex. Damage on the suckers is more pronounced than in PZQ-treated cestodes. The spines were completely removed. The current findings indicate that S. acmella is a good source of compounds with anthelmintic activity.

Chemical composition and broad-spectrum anthelmintic activity of a cultivar of toothache plant, Acmella oleracea, from Mizoram, India.

Context: A variety of Acmella oleracea (L.) R.K. Jansen (Asteraceae) is used by the Mizo people of India and Myanmar for intestinal helminthiasis.Objective: To perform a chemical analysis of the plant extract using gas chromatography-mass spectrometry (GC-MS) and test the anthelmintic activity on intestinal parasites.Materials and methods: An extract of the aerial parts was prepared in hexane and analysed using GC-MS. Survival test was performed in vitro on the cestode, Taenia tetragona, and the nematode, Ascaridia perspicillum. Concentrations of 1.25, 2.5, 5, 10 and 20 mg/mL, prepared in phosphate-buffered saline (PBS) with 1% dimethylsulphoxide (DMSO), were tested. Negative control was maintained in PBS with DMSO, and albendazole was used as a reference drug. Each treatment consisted of six worms and was done until death was confirmed. Scanning electron microscopy was used to describe the structural changes.Results: Nineteen compounds were detected. The major compounds were fatty alcohols such as 3,7,11,15-tetramethylhexadec-2-en-1-ol and (9Z)-9-hexadecen-1-ol. Important bioactive compounds including an alkylamide, N-isobutyl-(2E,4Z,8Z,10E)-dodecatetraenamide, and a triterpenoid, lupeol, were also confirmed. The lethal concentration (LC50) of the plant extract was 5128.61 ppm on T. tetragona and 8921.50 ppm on A. perspicillum. Tegumental shrinkage, erosion of microtriches, and distortion of the suckers were observed on the cestode. The nematode showed collapse of the lips and shrunk cuticle.Conclusions: Acmella oleracea contains important bioactive compounds, which are responsible for the broad-spectrum anthelmintic activity. Further study on the pharmacology of the compounds is warranted.

Histone deacetylase enzymes as potential drug targets of Neglected Tropical Diseases caused by cestodes.

Cestode parasites cause neglected diseases, such as echinococcosis and cysticercosis, which represent a significant problem in human and animal health. Benzimidazoles and praziquantel are the only available drugs for chemotherapy and it is therefore important to identify new alternative drugs against cestode parasites. Histone deacetylases (HDACs) are validated drug targets for the treatment of cancer and other diseases, including neglected diseases. However, knowledge of HDACs in cestodes is very scarce. In this work, we investigated cestode HDACs as potential drug targets to develop new therapies against neglected diseases caused by cestodes. Here we showed the full repertoire of HDAC coding genes in several members of the class Cestoda. Between 6 and 7 zinc-dependent HDAC coding genes were identified in the genomes of species from Echinococcus, Taenia, Mesocestoides and Hymenolepis genera. We classified them as Class I and II HDACs and analyzed their transcriptional expression levels throughout developmental stages of Echinococcus spp. We confirmed for the first time the complete HDAC8 nucleotide sequences from Echinococcus canadensis G7 and Mesocestoides corti. Homology models for these proteins showed particular structural features which differentiate them from HDAC8 from Homo sapiens. Furthermore, we showed that Trichostatin A (TSA), a pan-HDAC inhibitor, decreases the viability of M. corti, alters its tegument and morphology and produces an increment of the total amount of acetylated proteins, including acetylated histone H4. These results suggest that HDAC from cestodes are functional and might play important roles on survival and development. The particular structural features observed in cestode HDAC8 proteins suggest that these enzymes could be selectively targeted. This report provides the basis for further studies on cestode HDAC enzymes and for discovery of new HDAC inhibitors for the treatment of neglected diseases caused by cestode parasites.

Sheep enteric cestodes and their influence on clinical indicators used in targeted selective treatments against gastrointestinal nematodes.

Clinical indicators such as diarrhoea (DISCO) or anaemia (FAMACHA©) are used as a measure for targeted selective treatments against gastrointestinal nematodes (GIN). Enteric cestodes such as Moniezia may interfere directly with DISCO or indirectly with the FAMACHA© score. We investigated 821 Ouled Djellal rams naturally infected in a steppe environment (GIN alone, cestodes alone, GIN and cestodes) or not. The rams were treated with ivermectin 2 months before being slaughtered to reduce the impact of nematodes on the clinical scores; however, persistent or newly acquired GINs were not related to both scores. Of the non-infected rams (n = 296), 26% identified as needing treatment against GIN using the FAMACHA score, and 34.5% using DISCO would have been thus selected. This implies that the clinical indicators used for the targeted selective treatment of gastrointestinal nematodes are not fully reliable when a low infection is recorded and may well be influenced by confounding factors. As expected, only DISCO was affected by cestode infection, and we suggest that the presence of Moniezia should also be taken into consideration.

Dipylidium caninum Infection in Children: Clinical Presentation and Therapeutic Challenges.

Dipilidium caninum infection is a relatively uncommon parasitic infection in children. We present 10 cases treated in our tertiary care hospital during the last 2 years. This parasitosis has a relatively benign course but should be considered in children with gastrointestinal symptoms and eosinophilia. Treatment can be challenging, especially in infancy. Preventative measures are necessary to avoid the spread of the disease.

Praziquantel Resistance in the Zoonotic Cestode Dipylidium caninum.

Dipylidium caninum is a cosmopolitan cestode infecting dogs, cats, and humans. Praziquantel is a highly effective cestocidal drug and resistance in adult cestodes has not been reported. From 2016 to 2018, a population of dogs with cestode infections that could not be eliminated despite multiple treatments with praziquantel or epsiprantel was identified. Cases of D. caninum were clinically resistant to praziquantel and could not be resolved despite increasing the dose, frequency, and duration of treatment. Resistant isolates were identified and characterized by sequencing the 28S, 12S, and voltage-gated calcium channel beta subunit genes. Cases were only resolved following treatment with nitroscanate or a compounded pyrantel/praziquantel/oxantel product. Clinicians should be aware of this alarming development as treatment options for cestodes are limited in both human and veterinary medicine.

The genome of tapeworm Taenia multiceps sheds light on understanding parasitic mechanism and control of coenurosis disease.

Coenurosis, caused by the larval coenurus of the tapeworm Taenia multiceps, is a fatal central nervous system disease in both sheep and humans. Though treatment and prevention options are available, the control of coenurosis still faces presents great challenges. Here, we present a high-quality genome sequence of T. multiceps in which 240 Mb (96%) of the genome has been successfully assembled using Pacbio single-molecule real-time (SMRT) and Hi-C data with a N50 length of 44.8 Mb. In total, 49.5 Mb (20.6%) repeat sequences and 13, 013 gene models were identified. We found that Taenia spp. have an expansion of transposable elements and recent small-scale gene duplications following the divergence of Taenia from Echinococcus, but not in Echinococcus genomes, and the genes underlying environmental adaptability and dosage effect tend to be over-retained in the T. multiceps genome. Moreover, we identified several genes encoding proteins involved in proglottid formation and interactions with the host central nervous system, which may contribute to the adaption of T. multiceps to its parasitic life style. Our study not only provides insights into the biology and evolution of T. multiceps, but also identifies a set of species-specific gene targets for developing novel treatment and control tools for coenurosis.

Report: An ex vivo up-take of levamisole molecules by cestode (Monezia expensa) of goat (Capra hirsa) and its detection through RP-HPLC.

Detection of various molecules of drugs remained a prime issue especially in tissues of animals, humans and in their target parasites. The cestode/tapeworms pose a dilemma because of their weird body composition and uptake pattern of nutrients and medicines especially through absorption by tegument. We selected levamisole; thought to be potent antiparasitic/ani-cestodal drug. The uptake of levamisole (LEV) through cestodeal tissues is studied through HPCL in this paper. High performance liquid chromatography technique has been utilized to know the uptake of levamisole in tissues of cestodes of Goat (Monezia expensa) in small ruminants. The drug was exposed to M. expensa by in vitro till its death or a parasite ceases its movement. The tissue/ part of proglattids of the M. expensa were homogenized with some modifications and levamisole extraction was performed with liquid phase extraction method. The evaporation of solvent was done and the residual cestodal tissues were cleaned by solid phase. After the solid phase extraction method, the recovery of drug, detection and quantification of levamisole from cestodal tissues was determined through Reverse Phase Column High Performance Liquid Chromatography (RP-HPLC). Levamisole (LEV) molecules assay was obtained on a C18 reverse-phase (20um, 6mm x 150mm) column at flow rate of 1ml/min using acetonitrile and ammonium acetate as mobile phase and UV detection was done at 254nm. The development of method of Levamisole (LEV) detection from cestodal tissues by HPLC in vitro samples has been demonstrated first time in Pakistan, which can provide the solution of parasitic control and provide in sight in to the uptake of anti cestodal drugs either against human or livestock parasites.

Effect of (-)-epicatechin, a flavonoid on the NO and NOS activity of Raillietina echinobothrida.

(-)-Epicatechin, a natural flavonoid reportedly has huge pharmacological properties. In this study the cestocide effect of (-)-epicatechin is demonstrated in Raillietina echinobothrida. Although the antiparasitic activity of (-)-epicatechin has been demonstrated against protozoa, helminths and ectoparasites, in the present study the cestocide activity of (-)-epicatechin is shown to be related to a decrease in nitric oxide synthase (NOS) activity and nitric oxide (NO) production. On exposure to 0.53mg/ml each of epicatechin, reference drug praziquantel and Ñ  Nitro-l- Arginine Methyl Ester (NOS inhibitor), the parasites attained paralysis at 10.15, 0.27 and 11.21h followed by death at 30.15, 1.21 and 35.18h respectively. Biochemical analysis showed a significant decrease in activity of NOS (57.360, 36.040 and 44.615%) and NO (41.579, 19.078 and 24.826%) in comparison to the controls. NADPH-diaphorase histochemical staining (a selective marker for NOS in neuronal tissue) demonstrated a pronounced decline in the visible staining activity in the tegument, subtegument and the peripheral nerve regions following exposure to the treatments. Strong binding affinity of (-)-epicatechin with NOS protein was also revealed through docking studies. The results strongly define the probable anthelmintic activity of our compound through its influence on the NOS activity.

Preventive efficacy of NexGard Spectra® against Dipylidium caninum infection in dogs using a natural flea (Ctenocephalides felis) infestation model.

The efficacy of a monthly oral endectocide product, NexGard Spectra® (Merial), a combination of afoxolaner and milbemycin oxime, was evaluated in a flea (Ctenocephalides felis) challenge model for the prevention of Dipylidium caninum tapeworm infection in dogs. The efficacy of treatment with NexGard Spectra® was assessed in 10 dogs following weekly flea infestation with metacestode naturally infected fleas and compared with that in 10 untreated control dogs. The 100 fleas deposited weekly on each dog were not removed until Day 35, allowing enough time for their ingestion. The microscopical analysis of 30 fleas from the flea batches before each weekly challenge demonstrated that 10-33% of the fleas were infected by D. caninum cysticercoid larvae. The arithmetic mean flea count recorded was 47.7 for the 10 untreated dogs and 0 for the 10 treated dogs at Day 35. Based on the daily collection of expelled D. caninum proglottids by dogs during the 70 days of the study, 70% (7/10) of the control dogs and 0% (0/10) of the treated dogs were infected with D. caninum (p < 0.0031). Through its efficacy against fleas, NexGard Spectra® treatment provided indirect prevention of D. caninum infestation. No treatment-related adverse events were observed in dogs during this study.

Host pharmacokinetics and drug accumulation of anthelmintics within target helminth parasites of ruminants.

Anthelmintic drugs require effective concentrations to be attained at the site of parasite location for a certain period to assure their efficacy. The processes of absorption, distribution, metabolism and excretion (pharmacokinetic phase) directly influence drug concentrations attained at the site of action and the resultant pharmacological effect. The aim of the current review article was to provide an overview of the relationship between the pharmacokinetic features of different anthelmintic drugs, their availability in host tissues, accumulation within target helminths and resulting therapeutic efficacy. It focuses on the anthelmintics used in cattle and sheep for which published information on the overall topic is available; benzimidazoles, macrocyclic lactones and monepantel. Physicochemical properties, such as water solubility and dissolution rate, determine the ability of anthelmintic compounds to accumulate in the target parasites and consequently final clinical efficacy. The transcuticular absorption process is the main route of penetration for different drugs in nematodes and cestodes. However, oral ingestion is a main route of drug entry into adult liver flukes. Among other factors, the route of administration may substantially affect the pharmacokinetic behaviour of anthelmintic molecules and modify their efficacy. Oral administration improves drug efficacy against nematodes located in the gastroinestinal tract especially if parasites have a reduced susceptibility. Partitioning of the drug between gastrointestinal contents, mucosal tissue and the target parasite is important to enhance the drug exposure of the nematodes located in the lumen of the abomasum and/or small intestine. On the other hand, large inter-animal variability in drug exposure and subsequent high variability in efficacy is observed after topical administration of anthelmintic compounds. As it has been extensively demonstrated under experimental and field conditions, understanding pharmacokinetic behaviour and identification of different factors affecting drug activity is important for achieving optimal parasite control and avoiding selection for drug resistance. The search for novel alternatives to deliver enhanced drug concentrations within target helminth parasites may contribute to avoiding misuse, and prolong the lifespan of existing and novel anthelmintic compounds in the veterinary pharmaceutical market.

Ultrastructural changes in Raillietina (Platyhelminthes: cestoda), exposed to sulfonoquinovosyldiacylglyceride (SQDG), isolated from Neem (Azadirachta indica).

Neem (Azadirachta indica), has been known to be a curative for various ailments and diseases in the traditional Indian medicinal system from times immemorial. A glycolipid sulfonoquinovosyldiacylglyceride (SQDG) isolated from the leaves of neem has been found to be a proactive antibacterial and antiviral agent in previous studies. The current communication pertains to the anthelmintic activity of SQDG in vitro against a model cestode Raillietina spp. The results of efficacy tests showed a paralysis time of 1.0 ± 0.1 and 0.7 ± 0.01 h, whereas death time of 1.6 ± 0.3 and 0.9 ± 0.02 h, following treatments with dosages of 0.5 and 1.0 mg/mL, respectively. The scanning electron microscopic studies showed significant and unique changes in the ultrastructure of the worms with prominent breakages and furrows on the surface.

Anthelmintic efficacy of Clerodendrum viscosum on fowl tapeworm Raillietina tetragona.

CONTEXT: Clerodendrum viscosum Vent. (Verbenaceae) is a shrub, widely used amongst the natives of India against various diseases. OBJECTIVE: Crude extract of the plant was tested in vitro on a tapeworm Raillietina tetragona Molin (Davaineidae) to evaluate its potential anthelmintic efficacy and ultrastructural changes in the parasite. MATERIALS AND METHODS: Parasites were exposed to different concentrations of ethanolic leaf extract (10-80 mg/mL) and praziquantel (0.0005-0.005 mg/mL) and incubated in phosphate-buffered saline (PBS). The pH was 7.4 at 37 °C, while one set of worms was incubated only with PBS as a control. Permanent immobilization of worms was determined visually when no motility occurred on physically disturbing them. The parasites exposed to high concentrations of leaf extract and praziquantel treatments were processed for histological and electron microscopic studies, as these concentrations took the least time for paralysis and death to occur. RESULT: With an increase in the concentration of the leaf extract from 10 to 80 mg/mL and praziquantel from 0.0005 to 0.005 mg/mL, the time for the onset of paralysis and death was shortened. The treated parasites lost their spontaneous movement rapidly followed by death. Electron microscopic observations revealed disruptions in the tegument and parenchymal layer, accompanied by deformities in cell organelles. DISCUSSION AND CONCLUSION: Extensive structural alterations in the tegument indicate that the plant-derived components cause permeability changes in the parasite leading to paralysis and subsequent death. These observations suggest that phytochemicals present in C. viscosum have vermifugal or vermicidal activity, and thus may be exploited as alternative chemotherapeutic agents.

[ANTHELMINTIC SUBSTANCES: MAIN CLASSES, PROBLEMS, TRENDS IN DEVELOPMENT AND PROSPECTS].

The review chronologically considers the main classes of the currently available anthelminthic substances: early anthelmintic compounds, benzimidazoles, imidazolthiazoles, tetrahydropyrimidines, avermectins and milbemycins, and salicylanilides. Great attention is paid to novel substances (emodepside, monepantel, derquantel, tribendimidine) and promising developments. Some aspects of the molecular mechanisms of action of anthelmintics, their resistance, and alternative dehelmintization methods are discussed.

Praziquantel induced oxidative stress and apoptosis-like cell death in Raillietina echinobothrida.

Praziquantel (PZQ) is an anthelmintic drug used against trematode and cestode parasites of humans and veterinary animals. Since praziquantel was introduced as a broadspectrum anthelmintic, numerous studies described its successful use against helminth parasites, but its exact mechanism of action is feebly understood. Therefore, the present study was carried out to evaluate the possible role of PZQ induced oxidative stress in apoptosis-like cell death in the poultry tapeworm Raillietina echinobothrida. Parasite viability assay revealed a time-dependent reduction in the worm viability compared to the control. Transmission electron microscopy showed typical apoptotic features like condensed nucleus, damaged nuclear envelope and altered mitochondrial membrane in PZQ exposed parasites. Results revealed chromatin condensation and DNA fragmentation in PZQ exposed parasites. There was a notable decline in the level of glutathione and glutathione-s-transferase activity leading to the augmented generation of reactive oxygen species. This led to the alterations in the mitochondrial membrane potential with increased active caspase-3/7, confirms the involvement of mitochondria in the event. The present study suggests that PZQ exerts oxidative stress leading to apoptosis-like events in the parasites resulting their death.