Clinical efficacy of menthol and menthol-pentanol on Echinococcus multilocularis metacestodes

FABBRI, JULIA; CLEMENTE, CAMILA M.; RAVETTI, SOLEDAD; HERGERT, LISANDRO Y.; ELISSONDO, MARÍA C.

Buenos Aires

Congreso; Drug discovery for neglected disease international congress. 4th scientific meeting of the research network natural products against neglected diseases; 2018

Echinococcosis is a neglected disease caused by the larval stage of some species of parasites of the genus Echinococcus. Cystic echinococcosis is caused by E. granulosus and alveolar echinococcosis by E. multilocularis (Kern et al., 2017). Aromatic plants have been traditionally used for treatment of different diseases (Raut y Karuppayil, 2014). For several years, natural alternatives have been studied for treatment of echinococcosis. Essential oils (Pensel et al., 2014), their components (Fabbri et al., 2018) and structural modifications of these (derivatives) were assayed. Menthol, a cyclic monoterpene alcohol, is found in essential oils of some peppermint species, mainly Mentha piperita and M. arvensis. Menthol-pentanol is a new derivative of menthol, obtained by the carbonate binding of menthol and pentanol. In previous studies, menthol-pentanol showed a greater protoscolicidal effect than menthol. The aim of this work was to evaluate the clinical efficacy of menthol and menthol-pentanol against the murine model of alveolar echinococcosis. Protocols including animal management and procedures were approved by CICUAL (RD 148/15), FCEyN, UNMdP, Argentina. Fifty CF-1 female mice were infected by intraperitoneal inoculation with homogenized metacestode material (E. multilocularis J2012 strain) and divided among 5 experimental groups (10 animals/group): 1- Water control group; 2- Oil control group; 3- Albendazole (25 mg/kg) -carboxymethylcellulose (0.5% w/v) group; 4- Menthol (300 mg/kg); 5- Menthol-pentanol (300 mg/kg). Albendazole-carboxymethylcellulose suspension was prepared in deionized water and menthol and menthol-pentanol solutions in oil. Six weeks postinfection, treatments started and were performed daily during 4 weeks by intragastric administration. At the end of the treatment (10 weeks post-infection), mice were euthanized and the metacestodes were recovered. The efficacy of treatments was evaluated by comparing the weight of the cysts and by the ultrastructural alterations studied by scanning electron microscopy. Significant differences were observed between the weights of the cysts obtained from the control groups (water 3.30±1.47 gr; oil 2.84±1.25 gr) with respect to the albendazole-carboxymethylcellulose (0.98±0.4 gr) and menthol-pentanol (0.96±0.95 gr) groups. Treatment with menthol did not significantly reduce the weight of the cysts (1.24±0.94 gr). The ultrastructural study of cysts developed in all treated mice revealed the loss of cells of the germinal layer. Germinal layer of control cysts remained unaltered. The chemical modifications made on menthol to obtain menthol-pentanol allowed us to improve its effectiveness on the murine model of alveolar echinococcosis.