Volume 140, December 2014, Pages 61–67
Efficacy of albendazole in combination with thymol against Echinococcus multilocularis protoscoleces and metacestodes
Highlights
- •
- The anthelmintic activity of albendazole and/or thymol was demonstrated on E. multilocularis.
- •
- Combination of the two compounds showed the maximum anti-parasitic effect.
- •
- Drugs combined at 10 μg/ml caused dramatic alterations on protoscoleces and metacestodes.
Abstract
The larval (metacestode) stage of the tapeworm Echinococcus multilocularis
causes alveolar echinococcosis (AE), a mainly hepatic disease
characterized by continuous asexual proliferation of metacestodes by
exogenous budding, resulting in the tumor-like, infiltrative growth of
the parasite lesion. Current chemotherapeutical treatment of AE relies
on the use of benzimidazoles, albendazole (ABZ) and mebendazole, but
these drugs act parasitostatic rather than parasitocidal, and due to
their low success rate they imply a lifelong application causing severe
side effects. Thymol is one of the major components of the essential
oils of Thymus and is a widely known anti-microbial agent. The aim of
the present work was to compare the efficacy of albendazole (ABZ) and
thymol separately or combined on E. multilocularis
protoscoleces and metacestodes. For this purpose, microscopical
examinations at different time points were carried out. Moreover the
tegumentary enzyme gamma glutamyl transferase (GGT) was measured to
quantify the damage in metacestodes. Even though treatments of in vitro
cultured E. multilocularis protoscoleces or metacestodes with
ABZ or/and thymol showed that the drugs have an adverse effect on
parasite viability, the combination of the two compounds at the
concentration of 10 μg/ml showed the maximum anti-parasitic effect.
Three days postincubation the first effects of the treatment were
detected on protoscoleces and a marked reduction in viability (33%) was
registered at day 18. Incubation of E. multilocularis
metacestodes in the presence of ABZ 10 μg/ml + thymol 10 μg/ml during 10
days resulted in dramatic alterations such as strongly irregular and
fissured surface and markedly disrupted vesicles. Scanning electron
microscopy showed that protoscoleces as well as the germinal layer of E. multilocularis
metacestodes were dramatically damaged following ABZ or/and thymol
treatment. Also an important increase of tegumentary enzyme GGT was
registered after 72 h postincubation with both drugs. The data reported
in this article demonstrate a clear in vitro effect of ABZ + thymol
against E. multilocularis protoscoleces and metacestodes.
Graphical abstract
Keywords
- Echinococcus multilocularis;
- Protoscoleces;
- Metacestodes;
- Chemotherapy;
- Albendazole;
- Thymol
- Corresponding
author at: Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias
Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP),
Funes 3350, 7600 Mar del Plata, Argentina. Tel.:
+54 223 475 2426x450.
Copyright © 2014 Elsevier B.V. All rights reserved.
