Avaliação do potencial terapêutico do tiabendazol para tratamento da esquistossomose mansoni experimental

Abstract

Schistosomiasis is a neglected tropical disease, endemic in several countries, and generates serious socioeconomic consequences. The causative trematode belongs to the genus Schistosoma spp. The lack of a vaccine reinforces the role of chemotherapy in controlling morbidity and disease transmission. The most used drug is praziquantel, yet it does not have a pediatric dosage form. Its bitter taste and the size of the tablet contribute to keeping the treatment from being adhered to by children. Furthermore, praziquantel does not prevent reinfection. Consequently, another treatment option is necessary, thus, the effectiveness of the drug thiabendazole in the suspension form was evaluated, since it is intended for pediatric use. To verify the thiabendazole effectiveness, Swiss mice, preferably females, were infected with 80 ± 10 cercariae/animal. A total of 136 animals were divided into groups for different treatments, such as an uninfected and untreated group; a control group composed of infected and untreated animals; a positive control group with infected animals treated with a dose of praziquantel (400mg/Kg). The other groups of animals received oral doses of thiabendazole 50mg/kg and thiabendazole 100mg/kg after 30 days of infection, this period was intended for evaluating the effect of the treatment on young worms. Other groups received the same oral doses of thiabendazole 50mg/kg and thiabendazole 100mg/kg, however, the treatment was after 45 days of infection to evaluate the effect of the treatment on adult worms. The schistosomicidal action was analyzed after 7 days of treatment, through the euthanasia of the animals. The proposed thiabendazole treatment in both concentrations did not reduce the parasite load and did not interfere with oviposition. The liver and splenic weight analysis indicated an increase in these masses with the course of the infection when compared to the group G2. The study on the granuloma area revealed that the groups treated with TBZ had a smaller area. The production of antibodies was analyzed against the SEA and SWAP antigens and the groups G4 and G5 did not show significant reactivity when compared to group G2. Finally, the hepatotoxicity assay showed that TBZ in the used doses of 50 and 100 mg/kg did not show toxicity.In conclusion, the repositioning of the drug thiabendazole in the two-dose therapeutic scheme used at concentrations of 50 mg/kg and 100 mg/kg is not classified as a good therapeutic option in the fight against schistosomiasis mansoni. Given the data obtained, it is necessary to carry out new tests with this drug.