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

ALBANI CLARA MARÍA; PENSEL P.; ELISSONDO NATALIA; GAMBINO GUILLERMO; ELISSONDO MARIA CELINA

VETERINARY PARASITOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015

0304-4017

Human alveolar echinococcosis (AE) is caused bythe fox tapeworm Echinococcus multilocularis and isusually lethal if left untreated. The current strategy for treating human AE issurgical resection of the parasite mass complemented by chemotherapy with benzimidazolecompounds. However at present there is no chemotherapeutic option with 100 %effectiveness and this situation strongly stimulates the development of novel alternativessuch as the use of medicinal plants. The aim of the current study was toinvestigate the efficacy of the combination albendazole (ABZ) + thymol on miceinfected with E. multilocularismetacestodes. For this purpose, mice infected with parasite material were treateddaily 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 theperitoneal cavity and thetreatment efficacy was evaluated by the mean cysts weight, vitality ofprotoscoleces and ultrastructural changes of cysts and protoscoleces. The application of thymol or the combination of ABZ + thymol resultedin a significant reduction of the cysts weight compared to untreatedmice. We also found that although ABZ and thymol had a scolicidal effect, thecombination of the two compounds had a considerably stronger effect showing areduction in the protoscoleces viability of 62%. These results were alsocorroborated by optical microscopy, SEM and TEM. Protoscoleces recovered fromABZ or thymol treated mice showed alterations as contraction of the soma region,rostellar disorganization and presence of blebs in the tegument. However both drugswhen combined lead to a total loss of the typical morphology of protoscoleces. Allcysts removed from control mice appeared intact and no change in ultrastructurewas detected. In contrast, cysts developed in micetreated with ABZ revealed changes in the germinal layer as reduction in cellnumber, whilethe treatment with thymol or the ABZ + thymol combination predominantly showedpresence of cell debris. On the other hand, no differences were found inalkaline phosphatase (AP), glutamate oxaloacetatetransaminase (GOT) and glutamate pyruvate transaminase (GPT) activitiesbetween control and treated mice, indicating the lack of toxicity of thedifferent drug treatments during the experiment. Because combined ABZ + thymoltreatment exhibited higher treatment efficiency compared with the drugs appliedseparately against murineexperimental alveolar echinococcosis, we propose it would be a useful option forthe treatment of human AE.