Artículo

El editor solo permite decargar el artículo en su versión post-print desde el repositorio. Por favor, si usted posee dicha versión, enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Human alveolar echinococcosis (AE) is caused by the fox tapeworm Echinococcus multilocularis and is usually lethal if left untreated. The current strategy for treating human AE is surgical resection of the parasite mass complemented by chemotherapy with benzimidazole compounds. However, reliable chemotherapeutic alternatives have not yet been developed stimulating the research of new treatment strategies such as the use of medicinal plants. The aim of the current study was to investigate the efficacy of the combination albendazole (ABZ) + thymol on mice infected with E. multilocularis metacestodes. For this purpose, mice infected with parasite material were treated daily for 20 days with ABZ (5 mg/kg), thymol (40 mg/kg) or ABZ (5 mg/kg) + thymol (40 mg/kg) or left untreated as controls. After mice were euthanized, cysts were removed from the peritoneal cavity and the treatment efficacy was evaluated by the mean cysts weight, viability of protoscoleces and ultrastructural changes of cysts and protoscoleces. The application of thymol or the combination of ABZ + thymol resulted in a significant reduction of the cysts weight compared to untreated mice. We also found that although ABZ and thymol had a scolicidal effect, the combination of the two compounds had a considerably stronger effect showing a reduction in the protoscoleces viability of 62%. These results were also corroborated by optical microscopy, SEM and TEM. Protoscoleces recovered from ABZ or thymol treated mice showed alterations as contraction of the soma region, rostellar disorganization and presence of blebs in the tegument. However both drugs when combined lead to a total loss of the typical morphology of protoscoleces. All cysts removed from control mice appeared intact and no change in ultrastructure was detected. In contrast, cysts developed in mice treated with ABZ revealed changes in the germinal layer as reduction in cell number, while the treatment with thymol or the ABZ + thymol combination predominantly showed presence of cell debris. On the other hand, no differences were found in alkaline phosphatase (AP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities between control and treated mice, indicating the lack of toxicity of the different drug treatments during the experiment. Because combined ABZ + thymol treatment exhibited higher treatment efficiency compared with the drugs applied separately against murine experimental alveolar echinococcosis, we propose it would be a useful option for the treatment of human AE. © 2015 Elsevier B.V.

Registro:

Documento: Artículo
Título:In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis
Autor:Albani, C.M.; Pensel, P.E.; Elissondo, N.; Gambino, G.; Elissondo, M.C.
Filiación:Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, Mar del Plata, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Laboratorio de Análisis Clínicos Santisteban, Buenos Aires, Tandil, Argentina
Palabras clave:Albendazole; Alveolar echinococcosis; Echinococcus multilocularis; Liver enzymes; Thymol; alanine aminotransferase; albendazole; alkaline phosphatase; aspartate aminotransferase; thymol; albendazole; anthelmintic agent; thymol; animal cell; animal experiment; animal model; animal tissue; Article; autopsy; cell ultrastructure; cell viability; controlled study; drug efficacy; echinococcosis; Echinococcus multilocularis; enzyme activity; enzyme assay; female; in vivo study; metacestode; microscopy; mouse; nonhuman; peritoneal cavity; scanning electron microscopy; transmission electron microscopy; animal; combination drug therapy; echinococcosis; pathology; ultrastructure; Albendazole; Animals; Anthelmintics; Drug Therapy, Combination; Echinococcosis; Echinococcus multilocularis; Female; Mice; Thymol
Año:2015
Volumen:212
Número:3-4
Página de inicio:193
Página de fin:199
DOI: http://dx.doi.org/10.1016/j.vetpar.2015.06.030
Título revista:Veterinary Parasitology
Título revista abreviado:Vet. Parasitol.
ISSN:03044017
CODEN:VPARD
CAS:alanine aminotransferase, 9000-86-6, 9014-30-6; albendazole, 54965-21-8; alkaline phosphatase, 9001-78-9; aspartate aminotransferase, 9000-97-9; thymol, 89-83-8; Albendazole; Anthelmintics; Thymol
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044017_v212_n3-4_p193_Albani

Referencias:

  • Anthony, J., Fyfe, L., Smith, H., Plant active components-a resource for antiparasitic agents? (2005) Trends Parasitol. Rev., 21, pp. 462-468
  • Albani, C.M., Denegri, G.M., Elissondo, M.C., Effect of different terpene-containing essential oils on the proliferation of Echinococcus granulosus larval cells (2014) Interdiscip. Perspect. Infect Dis., 2014, p. 7. , Article ID 746931
  • Albani, C.M., Elissondo, M.C., Efficacy of albendazole and thymol combination against Echinococcus multilocularis protoscoleces and metacestodes (2014) Acta Trop., 140, pp. 61-67
  • Bessey, O.A., Lowry, O.H., Brock, M.J., A method for the rapid determination of alkaline phosphatase with five cubic millimeters of serum (1946) J. Biol. Chem., 164, pp. 321-329
  • Bergmeyer, H.U., Bowers, G.N., Horder, M., Moss, D.W., Provisional recommendations on IFCC methods for the measurement of catalytic concentrations of enzymes. Part 2. IFCC method for aspartate aminotransferase (1976) Clin. Chim. Acta, 70, pp. F19-F29
  • Casado, N., Rodriguez-Caabeiro, F., Hernandez, S., In vitro survival of Echinococcus granulosus protoscoleces (1986) Z. Parasitenkd., 72, pp. 273-278
  • Edris, A., Pharmaceutical and therapeutic potentials of essentials oils and their individual volatile constituents: a review (2006) Phytother. Res., 20, pp. 1-16
  • Elissondo, M.C., Ceballos, L., Dopchiz, M., Andresiuk, V., Alvarez, L., Sánchez Bruni, S., Lanusse, C., Denegri, G., In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes (2007) Parasitol. Res., 100, pp. 1003-1009
  • Elissondo, M.C., Albani, C.M., Gende, L., Eguaras, M., Denegri, G., Efficacy of thymol against Echinococcus granulosus protoscoleces (2008) Parasitol. Int., 57, pp. 185-190
  • Elissondo, M.C., Pensel, P.E., Denegri, G.M., Could thymol have effectiveness on scolices and germinal layer of hydatid cysts (2013) Acta Trop., 125, pp. 251-257
  • Garg, S., Anthelmintic activity of some medicinal plants (1997) Hamdard Med., 40, pp. 35-44
  • Gottstein, B., Wang, J., Blagosklonov, O., Grenouillet, F., Millon, L., Vuitton, D.A., Müller, N., Echinococcus metacestode: in search of viability markers (2014) Parasite, 21, p. 63
  • Hammond, J., Fielding, D., Bishop, S., Prospects for plant anthelmintics in tropical veterinary medicine (1997) Vet. Res. Commun., 21, pp. 213-228
  • Hemphill, A., Spicher, S., Stadelmann, B., Mueller, J., Naguleswaran, A., Gottstein, B., Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis (2007) Parasitology, 134, pp. 1657-1670
  • Hemphill, A., Stadelmann, B., Aeschbacher, D., Spiliotis, M., Gorgas, D., Albendazole and mebendazole: what else? Chemotherapy of echinococcosis: novel drugs on the horizon (2014) Innovation for the Management of Echinococcosis, 21, p. 93. , Parasite
  • Hübner, C., Wiehr, S., Kocherscheidt, L., Wehrl, H., Pichler, B.J., Schmid, A., Kern, P., Soboslay, P.T., Effects of in vitro exposure of Echinococcus multilocularis metacestodes to cytostatic drugs on in vivo growth and proliferation of the parasite (2010) Parasitol. Res., 107, pp. 459-463
  • Hulin, V., Mathot, A.G., Mafart, P., Dufosse, L., Les propriétés anti microbiennes des huiles essentielles et composés d'arômes (1998) Sci. Aliments, 18, pp. 563-582
  • Kern, P., Clinical features and treatment of alveolar echinococcosis (2010) Curr. Opin. Infect. Dis., 23, pp. 505-512
  • Küster, T., Stadelmann, B., Scholl, S., Barna, F., Kropf, C., Keiser, J., Boykin, D.W., Hemphill, A., In vitro and in vivo efficacies of mefloquine-based treatment against alveolar echinococcosis (2011) Antimicrob. Agents Chemother., 55, pp. 713-721
  • Küster, T., Kriegel, N., Boykin, D.W., Stephens, C.E., Hemphill, A., In vitro and in vivo activities of dicationic diguanidino compounds against Echinococcus multilocularis metacestodes (2013) Antimicrob. Agents Chemother., 57, pp. 3829-3835
  • Maggiore, M.A., Albanese, A.A., Gende, L.B., Eguaras, M.J., Denegri, G.M., Elissondo, M.C., Anthelmintic effect of Mentha spp. essential oils on Echinococcus granulosus protoscoleces and metacestodes (2012) Parasitol. Res., 110, pp. 1103-1112
  • Maggiore, M., Elissondo, M.C., In Vitro cestocidal activity of thymol on Mesocestoides corti tetrathyridia and adult worms (2014) Interdiscip. Perspect. Infect. Dis., 2014, p. 8. , Article ID 268135
  • Maggiore, M., Pensel, P., Denegri, M.G., Elissondo, M.C., Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis (2015) Parasitol. Inter., 64, pp. 435-440
  • Moazeni, M., Larki, S., Saharkhiz, M.J., Oryan, A., Ansary Lari, M., Mootabi Alavi, A., In vivo study of the efficacy of the aromatic water of Zataria multiflora on hydatid cysts (2014) Antimicrob. Agents Chemother., 58, pp. 6003-6008
  • (2011) Guide for the Care and Use of Laboratory Animals, , National Academies Press (US), Washington (DC)
  • Pensel, P.E., Maggiore, M.A., Gende, L.B., Eguaras, M.J., Denegri, M.G., Elissondo, M.C., Efficacy of essential oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus (2014) Interdiscip. Perspect. Infect. Dis, 2014, p. 12. , Article ID 693289
  • Pessoa, L., Morais, S., Bevilaqua, C., Luciano, J., Antihelmintic activity of essential oil Ocimum gratissimun Linn. and eugenol against Haemonchus contortus (2002) Vet. Parasitol., 109, pp. 59-63
  • Reuter, S., Beisler, T., Kern, P., Combined albendazole and amphotericin B against Echinococcus multilocularis in vitro (2010) Acta Trop., 115, pp. 270-274
  • Robledo, S., Osorio, E., Muñoz, D., Jaramillo, L.M., Restrepo, A., Arango, G., Vélez, I., In vitro and in vivo cytotoxicities and antileishmanial activities of thymol and hemisynthetic derivatives (2005) Antimicrob. Agents Chemother., 49, pp. 1652-1655
  • Spicher, M., Roethlisberger, C., Lany, C., Stadelmann, B., Keiser, J., Ortega-Mora, L.M., Gottstein, B., Hemphill, A., In vitro and in vivo treatments of echinococcus protoscoleces and metacestodes with artemisinin and artemisinin derivatives (2008) Antimicrob. Agents Chemother., 52, pp. 3447-3450
  • Spicher, M., Naguleswaran, A., Ortega-Mora, L.M., Müller, J., Gottstein, B., Hemphill, A., In vitro and in vivo effects of 2-methoxyestradiol, either alone or combined with albendazole, against Echinococcus metacestodes (2008) Exp. Parasitol., 119, pp. 475-482
  • Stettler, M., Rossignol, J.F., Fink, R., Walker, M., Gottstein, B., Merli, M., Theurillat, R., Hemphill, A., Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity (2004) Int. J. Parasitol., 34, pp. 615-624
  • Torgerson, P.R., Schweiger, A., Deplazes, P., Pohar, M., Reichen, J., Ammann, R.W., Tarr, P.E., Müllhaupt, B., Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years (2008) J. Hepatol., 49, pp. 72-77
  • Torgerson, P.R., Keller, K., Magnotta, M., Ragland, N., The global burden of alveolar echinococcosis (2010) PLoS Negl. Tropic. Dis., 4, p. e722

Citas:

---------- APA ----------
Albani, C.M., Pensel, P.E., Elissondo, N., Gambino, G. & Elissondo, M.C. (2015) . In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis. Veterinary Parasitology, 212(3-4), 193-199.
http://dx.doi.org/10.1016/j.vetpar.2015.06.030
---------- CHICAGO ----------
Albani, C.M., Pensel, P.E., Elissondo, N., Gambino, G., Elissondo, M.C. "In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis" . Veterinary Parasitology 212, no. 3-4 (2015) : 193-199.
http://dx.doi.org/10.1016/j.vetpar.2015.06.030
---------- MLA ----------
Albani, C.M., Pensel, P.E., Elissondo, N., Gambino, G., Elissondo, M.C. "In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis" . Veterinary Parasitology, vol. 212, no. 3-4, 2015, pp. 193-199.
http://dx.doi.org/10.1016/j.vetpar.2015.06.030
---------- VANCOUVER ----------
Albani, C.M., Pensel, P.E., Elissondo, N., Gambino, G., Elissondo, M.C. In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis. Vet. Parasitol. 2015;212(3-4):193-199.
http://dx.doi.org/10.1016/j.vetpar.2015.06.030