title: In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis.
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.
authors.affiliation: Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Clara María
authors.initials: CM
authors.lastname: Albani
authors.affiliation: Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Patricia Eugenia
authors.initials: PE
authors.lastname: Pensel
authors.affiliation: Laboratorio de Análisis Clínicos Santisteban, 7000 Tandil, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Elissondo
authors.affiliation: Laboratorio de Análisis Clínicos Santisteban, 7000 Tandil, Buenos Aires, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gambino
authors.affiliation: Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: mceliss@mdp.edu.ar.
authors.forename: María Celina
authors.initials: MC
authors.lastname: Elissondo
mesh_terms: D015766:Albendazole / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004443:Echinococcosis / Q000188:drug therapy* / Q000473:pathology; D048210:Echinococcus multilocularis / Q000648:ultrastructure; D005260:Female; D051379:Mice; D013943:Thymol / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000871:Anthelmintics; D013943:Thymol; D015766:Albendazole
keywords: Albendazole; Alveolar echinococcosis; Echinococcus multilocularis; Liver enzymes; Thymol