Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis

Maggiore, Marina A.; Pensel, Patricia Eugenia; Denegri, Guillermo M.; Elissondo, Marı́a Celina

doi:10.1016/j.parint.2015.06.005

Cited by 18 publications

(12 citation statements)

References 34 publications

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“…The ultrastructural changes observed by electron microscopy included the loss of the characteristic multicellular appearance of the germinal layer, distorted internal tissue with presence of vacuolated areas and depletion of glycogen reserves. This results coincide with the observed alterations in other chemoprophylactic studies againts the murine model of CE (Urrea-Paris et al, 2001;Ceballos et al, 2010;Moazeni et al, 2014;Pensel et al, 2014;Maggiore et al, 2015). Moreover, the viability of E. multilocularis protoscoleces isolated from ABZ-NC treated mice was significantly lower than that from control…”

Section: Multilocularissupporting

confidence: 88%

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Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice

Pensel

Paredes

Albani

et al. 2018

Veterinary Parasitology

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Human alveolar echinococcosis is caused by the fox tapeworm Echinococcus multilocularis and is usually fatal if left untreated. Medical treatment with albendazole (ABZ) remains an effective option. However, due to its low aqueous solubility, ABZ is poorly and erratically absorbed following oral administration resulting in low drug levels in plasma and liver distribution. Thus, there arises the need to find a simple, efficient and scalable method to produce new ABZ formulations with increased bioavailability. Bearing this in mind, ABZ nanocrystals (ABZ-NCs) appears to be a useful tool to achieve this goal. The aim of the current study was to investigate the chemoprophylactic and clinical efficacy of an ABZ-NC formulation on mice infected with E. multilocularis. In the chemoprophylactic efficacy study, mean weight of the cysts recovered from the ABZ-NC group was 50% lower than that recorded from untreated mice, whereas the treatment with ABZ suspension did not show preventive effect. The viability of protoscoleces isolated from ABZ-NC treated mice was significantly lower than control groups. In the clinical efficacy studies, both ABZ formulations resulted in a reduction in the mean weight of the cysts obtained from mice, however only the treatment with the nanosuspension revealed significant differences (P < 0.05) compared to the control groups. Treatment with ABZ-NCs reduced the weight of the cysts by 77% and the viability of their protoscoleces to 34%. All these results coincided with the tissue damage determined at the ultrastructural level. The enhanced chemoprophylactic and clinical efficacy of ABZ-NCs observed in this study could be attributed to an increase in the oral bioavailability of the drug. In a next step, we will characterize the cyst concentration profile after the administration of ABZ-NCs in mice infected with E. multilocularis.

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Section: Multilocularissupporting

confidence: 88%

“…A deleterious drug effect on protoscoleces at the time of infection could explain the development of anomalous cysts and protoscoleces (Maggiore et al, 2015).…”

Section: Multilocularismentioning

confidence: 99%

Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice

Pensel

Paredes

Albani

et al. 2018

Veterinary Parasitology

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“…Earlier in vitro and in vivo investigations had already demonstrated the effectiveness of thymol against E. granulosus protoscoleces and hydatid cysts (Elissondo et al, 2008;Maggiore et al, 2015), Mesocestoides corti tetrathyridia and adult worms , and also promising in vitro results were obtained using the combination ABZ + thymol on E. multilocularis protoscoleces .…”

Section: Discussionmentioning

confidence: 99%

“…Thymol (2-isopropyl-5-methylphenol) is one of the major components of the essential oils of Thymus vulgaris and Origanum vulgare and it has been proved to have a strong in vitro and in vivo effect against protoscoleces, microcysts and cysts of E. granulosus (Elissondo et al, 2008;Maggiore et al, 2015). Recently, encouraging findings have been reported using combined drugs ABZ + thymol on E. multilocularis protoscoleces and metacestodes in vitro .…”

Section: Introductionmentioning

confidence: 99%

In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis

Albani

Pensel

Elissondo³

et al. 2015

Veterinary Parasitology

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“…Pharmacological studies of carvacrol showed that it possesses an antiparasitic effect [2,12]. Furthermore studies have shown that thymol demonstrated its effi cacy against experimental murine cystic echinococcosis and is a potential alternative for the treatment of human hydatid disease [13]. P-cymene, in a blend of active ingredients of four plants EOs, shows the ability to reduce infection burdens of soil transmitted helminths in pigs [14], while cinnamaldehyde has potent in vitro antinematodal activity [11].…”

Section: Introductionmentioning

confidence: 99%

Antihelminic Activity of Carvacrol, Thymol, Cinnamaldehyde and P-Cymen Against the Free-Living Nematode Caenorhabditis elegans and Rat Pinworm Syphacia muris

et al. 2018

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In the present study we tested the dose andh time dependence of the antinematodal effects of carvacrol and tyhmol on Caenorabditis elegans, and the efficacy of carvacrol, thymol, p-cymene and cinnamaldehyde,which were administrated in the drinking water of rats naturally infected with the pinworm Syphacia muris. The control treatment of the infected rats was carried out with piperazine. Thymol caused a dose and time-dependent mortality in adult C. elegans. The value of the Median Lethal Concentration (LC50) of thymol was 117.9nM after 24h and 62.89 nM after 48h of exposure. Carvacrol exhibited a higher antinematodal efficiency than thymol. The LC50 of carvacrol, after 24 hours of exposure, was 53.03 nM, while after 48 hours it was 33.83 nM. On the other hand, piperazine showed an extremely high efficacy against S. muris infection in rats. Piperazine, at a dose of 625 mg/kg bw, administered in drinking water continuously for 10 days, eliminates the infection completely. However, none of the investigated active ingredients of essential oils were effective against S. muris. The reason for the lack of efficiency may be due to their pharmacokinetic properties. A relatively low amount of, orally administered, active ingredients of essential oils reaches the distal segments of the gastrointestinal tract, where S. muris inhabits the gut (colon and cecum). The obtained results, on C. elegans, indicate a clear dose and time-dependent antinematodal effect of thymol and carvacrol. However, for clinical application, it is necessary to examine the efficacy of microencapsulated formulations with a controlled release of active ingredients of essential oils in certain parts of the gastrointestinal tract.

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Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis

Cited by 18 publications

References 34 publications

Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice

Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice

In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis

Antihelminic Activity of Carvacrol, Thymol, Cinnamaldehyde and P-Cymen Against the Free-Living Nematode Caenorhabditis elegans and Rat Pinworm Syphacia muris

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